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Vol. 45. Issue 6.
Pages 602-615 (November - December 2017)
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Vol. 45. Issue 6.
Pages 602-615 (November - December 2017)
DOI: 10.1016/j.aller.2017.01.006
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Epidemiology and pathophysiology of malignancy in common variable immunodeficiency?
A. Tak Manesha, G. Azizib,c, A. Heydaric, F. Kiaeec, M. Shaghaghic, N. Hossein-Khannazerd, R. Yazdanie, H. Abolhassanic,f, A. Aghamohammadic,
Corresponding author

Corresponding author.
a Member of RACGP, Melbourne, Australia
b Department of Laboratory Medicine, Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran
c Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
d Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
e Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
f Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
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Figures (1)
Tables (2)
Table 1. Frequency of different types of malignancy among different cohorts of CVID patients.
Table 2. The most common genetic mutations associated with malignancies in CVID patients.
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Common variable immunodeficiency (CVID) is a diagnostic category of primary immunodeficiency (PID) which may present with heterogeneous disorders including recurrent infections, autoimmunity, granulomatous diseases, lymphoid and other types of malignancies. Generally, the incidence of malignancy in CVID patients is around 1.5–20.7% and usually occurs during the 4th–6th decade of life. Non-Hodgkin lymphoma is the most frequent malignancy, followed by epithelial tumours of stomach, breast, bladder and cervix. The exact pathological mechanisms for cancer development in CVID are not fully determined; however, several mechanisms including impaired genetic stability, genetic predisposition, immune dysregulation, impaired clearance of oncogenic viruses and bacterial infections, and iatrogenic causes have been proposed to contribute to the high susceptibility of these patients to malignancies.

Common variable immunodeficiency
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Common variable immunodeficiency (CVID) is a diagnostic category of primary immunodeficiency (PID) that includes heterogeneous disorders defined by increased susceptibility to recurrent infection, low levels of immunoglobulin (Ig) in serum and impaired specific antibody responses to pathogens or vaccines.1–4 Patients may also have a wide variety of non-infectious complications, including autoimmunity and inflammatory conditions, enteropathy, granulomatous diseases, lymphoid malignancies and different types of cancers.5,6 Malignancy has been proposed as a distinct clinical phenotype of CVID due to underlying genetic predisposing factor which influences mortality and morbidity of patients, but it is argued that this phenotype could be a secondary consequence to viral infections or immune dysregulation.7

Several studies report a high frequency of malignancy in CVID patients.8–16 Generally, the incidence of cancer in these patients is around 10% (range 1.5–20.7%, Table 1) and usually occurs during the 4–6th decade of life, with a risk 5–12 times higher than in the general population.12,17 In two large cohorts in New York and Italy, the incidence of cancers was noted to be 15.2% and 20.7% in CVID patients, respectively.14,18 The most common site of malignancy is lymphoid tissues.19–21 Recent studies reported that Non-Hodgkin lymphoma (NHL) is the most frequent malignancy, followed by epithelial tumours of stomach, breast, bladder and cervix. Among epithelial tumours in CVID patients, gastric adenocarcinoma is the most prevalent cancer.14,21–23 In fact, the cumulative incidence of cancers in CVID appears to have expanded, but the data for cancers other than lymphoma are difficult to separate out.24 However, in the New York study the frequency of other malignancies was reported about 7%,14 and 3% in the European Society for immunodeficiencies study.5 In a study by the Australasian Society of Clinical Immunology and Allergy (ASCIA), the increased risks of malignancies in CVID patients compared to the population without CVID were identified as 12-fold for NHL, 7-fold for stomach cancer, 2.49-fold for leukaemia, 2.24-fold for breast cancer, and surprisingly, 146-fold for thymus cancer.17

Table 1.

Frequency of different types of malignancy among different cohorts of CVID patients.

Study  Year  Total CVID patients  Total cancer patients  NHL  HL  Other types or unspecified lymphoma  Gastric adenocarcinoma  Other GI cancer  Breast cancer  Other gynaecological cancers  Melanoma  Other skin cancer  Lung cancer  Unspecified solid tumours 
Cunningham-Rundles et al.34  1999  248  41 (16.5)  19 (7.6)  3 (1.2)  –  2 (0.8)  3 (1.2)  –  2 (0.8)  1 (0.4)  2 (0.8)  1 (0.4)  8 (3.2) 
Kokron et al.162  2004  71  6 (8.4)  1 (1.5)    2 (3)  1 (1.5)  –  –  –  1 (1.5)  –  –  1 (1.5) 
Quinti et al.10  2007  224  14 (6.2)  4 (1.7)  –  2 (0.8)  2 (0.8)  2 (0.8)  2 (0.8)  1 (0.4)  –  –  –  1 (0.4) 
Oksenhendler et al.163  2008  252  39 (15.4)  –  –  16 (6.3)  –  –  –  –  –  –  –  23 (9.1) 
Chapel et al.5  2008  334  6 (1.8)  –  –  3 (0.9)  –  –  –  –  –  –  –  3 (0.9) 
Vajdic et al.17  2010  416  38 (9.1)  11 (2.6)  –  1 (0.2)  2 (0.5)  –  9 (2.2)  –  –  –  –  2 (0.5) 
Resnick et al.14  2012  473  72 (15.2)  26 (5.4)  4 (0.8)  9 (1.9)  3 (0.6)  5 (1.0)  9 (1.9)  2 (0.4)  3 (0.6)  1 (0.2)  1 (0.2)  9 (1.9) 
Quinti et al.164  2012  353  63 (20.7)  –  –  –  5 (1.4)  –  –  –  –  –  –  – 
Abolhassani et al. 15  2012  93  8 (8.6)  4 (4.3)  –  –  3 (3.2)  –  1 (1.0)  –  –  –  –  – 
Rivoisy et al.165  2012  436  26 (6.0)  –  –  25 (5.7)  –  –  –  –  –  –  –  1 (0.2) 
Sini et al.166  2013  144  7 (4.8)  6 (4.1)  1 (1.4)  –  –  –  –  –  –  –  –  – 
Gathmann et al.128  2014  2212  203 (9.1)  –  –  71 (3.2)  –  –  13 (0.5)  –  –  20 (0.9)  –  99 (4.4) 
López-Rocha et al.20  2015  23  4 (17.3)  –  1 (4.3)  1 (4.3)  –  1 (4.3)  –  –  –  –  –  1 (4.3) 

In this study, we sought to demonstrate the epidemiology and aetiology of common types of malignancies in CVID patients by reviewing the most recent evidence on this topic.

Mechanisms of increased susceptibility of CVID patients to malignancy

The exact pathological mechanisms of malignancy in CVID are not fully determined; although several mechanisms have been suggested to contribute to the high susceptibility of these patients to specific types of malignancies.16 These mechanisms include innate genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections (Fig. 1).

Figure 1.

Mechanisms of susceptibility of CVID patients to malignancy. Several mechanisms have been suggested to contribute to the high susceptibility of CVID patients to malignancies. These mechanisms include genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections.

Impaired function of immune system

Impaired immune response results in decreased clearance of oncogenic viruses and bacteria, as well as chronic antigen stimulation, chronic inflammatory response, and survival and proliferation of premalignant and malignant cells, all of which can predispose CVID patients to oncogenic mutations and malignant transformations.25–29 The key cells of the immune system for tumour surveillance are natural killer (NK) cells and CD8+ T cells, which are parts of the innate and adaptive immune response. After recognition of a tumour antigen via the T cell receptor (TCR), activated CD8+ cytotoxic T cells can kill the tumour target cells. Moreover, CD4+ T cells, especially T helper cell type 1 (Th1), provide “help” for the activation of CD8+ T cells, and can display cytotoxic activity in some situations.30–32 However, defects in CD4+ T cells and CD8+ T cells immunity, which occur in approximately one-third of CVID patients, possibly contribute to their susceptibility to malignant complications.33–35 In addition, the frequency of NK cells, as other tumour killer cells has been reported to be lower in CVID.36,37 However, data of 801 CVID patients from the national UK Primary Immune Deficiency (UKPID) registry showed that, overt cancer is associated with significantly lower absolute CD8+ T cell but not NK cell numbers, raising the question as to what extent immune senescence, especially of CD8+ T cells, might contribute to the increased risk of cancers.38

There are multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases, and cancer development.39 It is demonstrated that the risks of all NHL increases in association with rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, and celiac disease.40 All of these conditions are also associated with CVID.41,42 In addition, the use of nonsteroidal anti-inflammatory drugs, systemic corticosteroids, and immunosuppressive medications was shown to be associated with risk of NHL in rheumatoid arthritis patients.40

Viral and bacterial infections

Infections with certain type of viruses and bacteria have been recognised as risk factors for several types of cancer in different ways; when some viruses directly affect the genes inside cells and cause them to grow out of control, other infectious organisms can cause long-term inflammation which leads to changes in the infected cells and in nearby immune cells, and eventually lead to cancer.43–45 It is demonstrated that chronic inflammation can promote all stages of tumorigenesis including apoptosis evasion, sustained angiogenesis, DNA damage, limitless replication, self-sufficiency in growth signalling, and insensitivity to anti-growth signalling, as well as tissue invasion and/or metastasis.46 In addition, some types of bacterial and viral infections can suppress patient immune system, and therefore help to the development of cancers.47,48

Although immunoglobulin therapy greatly reduces the episodes of infections and enhances patients’ survival, it does not appear to address the development of cancer, especially lymphoma. The definite reason for the increased susceptibility to lymphoid malignancies is unclear. The proposed mechanism includes genetics, radiosensitivity, immune dysregulation, and chronic infections such as Helicobacter pylori, Epstein–Barr virus (EBV), human herpes virus type 8 (HHV8) and cytomegalovirus (CMV). Up to now, the strongest association between chronic bacterial infection and the development of cancer involves H. pylori, which is associated with increased risk of adenocarcinoma of the stomach and mucosa-associated lymphoid tissue (MALT) lymphoma.49–52 It is suggested that the robust immune response generally fails to clear the H. pylori infection, leading to a chronic inflammatory response which is thought to be a key element of the carcinogenic activity of the bacterium. H. pylori infection is commonly found in CVID patients with chronic gastritis complication10,53,54; therefore, it may account for the increased incidence of gastric cancer and extra-nodal marginal zone lymphoma in these patients.55–57

Many different types of viruses may cause an increased risk of cancer by directly transforming the cells they infect, or by causing a chronic inflammatory condition, or both. Those most commonly associated with chronic inflammation are the hepatitis B and C viruses, which result in chronic active hepatitis and hepatocellular carcinoma.58,59 The prevalence of hepatitis is also increased in CVID, occurring in nearly 12% of patients.60–62 Among viral infections, EBV is associated with nasopharyngeal cancer and certain types of lymphomas such as Hodgkin and NHL, and may also contain a chronic inflammatory component.63,64 It is revealed that EBV causes sustained proliferation of peripheral B cells, but when coupled with a secondary mutation led to malignant transformation; such as the occurrence with chromosomal translocations that activate the c-myc oncogene in Burkitt's lymphoma.65 Other viral infections such as the CMV, human papillomavirus (HPV) and herpes simplex virus have been implicated in the increased incidence of cervical and other carcinomas.66,67 Moreover, HHV8 has been found in nearly all tumours in patients with Kaposi sarcoma.68 However, there are few reports of viral infections such as EBV,69 HHV8,70 HPV71 and CMV72,73 to induce an increased risk of malignancy in CVID patients.33,55

Genetic predisposition

A genetic predisposition to some types of malignancies is a probable aetiology of cancer in some PID patients, although not usually as a result of oncogenic genes. Instead, other mechanisms such as the presence of certain mutations or defective tumour suppressor genes appear to be involved.74,75 Certain mutations in the specific genes such as BRCA1, BRCA2, BARD1 and BRIP1 greatly increase a person's risk of developing breast cancer and ovarian cancer, but the contribution of these genetic changes to CVID patients’ overall risk is not investigated. Mutations in a main tumour suppressor gene, tumour protein p53 (TP53) encoding for p53 protein, are one of the most common genetic variations in human cancers, and contribute to the complex network of molecular events leading to tumour formation.76 In numerous studies, defects in p53 have been reported in gastric cancer from Japan,77 Portugal76 and Germany.78 Zullo et al.54 hypothesised that p53 alterations can play a role in the gastric carcinogenesis of patients with CVID. However, in a study by Kilic et al. they found no statistically significant correlation between the presences of TP53 mutations in CVID patients, also none of the 20 CVID patients were found to have TP53 gene mutations. In addition, TP53 mutations were not detected in tumour biopsy. However, during nine years follow-up, one patient developed non-Hodgkin lymphoma.79 Genetic variation in other genes including B-cell lymphoma 2 (BCL2), B-cell lymphoma 6 (BCL6),80,81TNF, LTA, NFKB1,82 and PFTK1 (Table 2) which are reported in some types of malignancy are also associated with CVID.83–85

Table 2.

The most common genetic mutations associated with malignancies in CVID patients.

Study  Year  Mutated gene  Related malignancy 
Zullo et al.54  1999  TP53  Gastric cancer 
Ariatti et al.83  2000  BCL-6  Non-Hodgkin lymphoma 
Ariatti et al.151  2001  *MGMT, DAP-kinase, GSTp1  Non-Hodgkin lymphoma 
Orange et al.85  2011  KIAA0834, PFTK1, HAVCR1  Lymphoma 
da Silva et al.150  2011  ORC4L  Lymphoproliferative disorders 
Fliegauf et al.84  2015  NFKB1  Squamous cell carcinoma, Lung adenocarcinoma, Non-Hodgkin lymphoma 
Toh et al.153  2016  RUNX1, ASXL1  Myelodysplastic syndrome 

Promoter hypermethylation.

Evidence demonstrates that family history of malignancy35 as well as some autoimmune and chronic inflammatory diseases including celiac disease, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, psoriasis and autoimmune cytopenias are associated with the development of malignancy.39,84,86–88 The prevalence of autoimmune diseases in patients with CVID is higher than 20% reported in the literature.89 Therefore haematological malignancies especially NHL and Hodgkin lymphomas should be suspected in CVID patients, since half of CVID patients with autoimmunity presented autoimmune haematological diseases including autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP).90–93 However, there has been no report of a long-term follow-up cohort study in CVID patients to confirm the incidence of haematological malignancies following autoimmune disorders.

Genetic instability

The higher incidence of cancer in CVID cases has also been explained by genomic instability. It is manifested by an increased level of chromosomal damage after mutagenic stresses like radiation or chemical agents in the environment, as well as from endogenous DNA-damaging agents that arise by-products of cellular metabolism.94–97 There are several reports which indicate radiosensitivity of DNA in CVID patients after exposure to radiation98–100 and its involvement with malignancy progress.55,95,101

In CVID patients, a dose-dependent chromosomal instability was demonstrated by in vitro irradiation of lymphocytes.98 Irradiated lymphocytes show higher chromosomal aberrations and lower mitotic indices than lymphocytes of control, indicating an increased chromosomal radiosensitivity in some CVID patients.99,102 The impact of these findings could be greatly improved by identifying the underlying genetic cause of radiation sensitivity in CVID patients. Recently, the cause of radiosensitivity in CVID patients is explained as defects in DNA repair pathways, which acts as the primary response to ionising radiation in healthy individuals.95,102 It is demonstrated that ionising radiation induces a broad spectrum of lesions in DNA, and double strand breaks (DSBs) represent the most significant lethal lesions.97 The main mechanism for the repair of DSBs in DNA is non-homologous end-joining (NHEJ), a process that rejoins breaks with the use of little or no homology. The main proteins that operate in NHEJ are Ku70, Ku80 and DNA-dependent protein kinase (DNA-PK) complex, as well as XRCC4 and DNA ligase IV.97,103,104

In a recent study, Van Schouwenburg et al.105 identified five CVID patients with heterozygous variants in genes which are involved in NHEJ. They also found variants in DCLRE1C, PRKDC, RAG2, NHEJ1, MRE11A, ATM and NLRP2 genes in CVID patients. All these genes are important in the initiation of V(D)J recombination or DSB repair by NHEJ. As NHEJ is essential in DNA repair, inefficient NHEJ may lead to malignant conditions in a subgroup of CVID patients.106 In 2011, Duvvuri et al. provided evidence that some CVID patients have defective repair of activation-induced cytidine deaminase (AID)-induced mutations, which is directed by the DNA mismatch repair machinery including mutS homolog 2 and 6 (MSH2/MSH6), Exonuclease 1 (EXO1), and MutL homolog 1 (MLH1)/PMS2.107 Moreover, some mutations in genes of the Mre11-Rad50-Nbs1 (MRN) complex and the homologous recombination pathway as well as MSH5 gene have been reported in CVID.101,108 Paradoxically, Nemati et al.109 did not confirm the previously observed association between the RAD50 and development of CVID in an Iranian population. However, a growing body of evidence shows the importance of DNA mismatch repair in the pathogenesis of CVID, at least in subgroups of these patients.110 Altogether, defective repair of AID-induced mutations with reports of increased chromosomal radiation sensitivity and associated lymphoproliferative disorders in CVID patients, suggest that altered DNA damage repair may be a cause of malignancy in CVID.107

Most common malignancies in CVIDGastric cancer

Based on an epidemiological data from the American Cancer Society, gastric cancer is the fourth most common type of cancer in males and the fifth most common form in females, accounting for 6.8% of the total cancer cases and 8.8% of total cancer-related deaths in 2012 globally.111–113 Several studies reported increased risk of gastric cancer (7–47-fold) in CVID patients.12,17,114,115 In a large study during 1990–2008 by ASCIA registry, of 416 studied CVID patients from 79 centres in Australia, a seven-fold increase in the risk of gastric cancer has been reported.17 In other studies, Bonilla et al. in 2005 and Mellemkjaer et al. in 2002 reported a 10-fold increased risk of gastric cancer and more precisely gastric carcinoma in patients with CVID.12,115 However, an old study in 1985 showed surprisingly higher results. During 11 years follow-up of 220 CVID patients, a 47-fold increase in the risk of gastric cancer was reported.114 Moreover, the Standardised Incidence Ratio (SIR) of gastric adenocarcinoma in CVID patients in Sweden and Denmark was equal to 10.3.12

There are modifiable and non-modifiable risk factors for gastric cancer in the general population. Non-modifiable include advanced age, male gender, genetic predisposition, blood group A, radiation, lower socio-economic status, gastric surgery and a history of EBV infection. Modifiable risk factors include H. pylori infection, smoking, pernicious anaemia, diet (consumption of salt-preserved foods and N-nitroso compounds), and geography.116,117 Other than those mentioned, there are some risk factors which are more relevant to gastric cancer in CVID. These CVID-associated factors include pernicious anaemia, gastric atrophy, achlorhydria, decreased gastric IgA, and chronic H. pylori infection.17,118 Moreover, mutations in tumour suppressor TP53 gene have been reported to be related to an increased risk of gastric cancer in CVID. In a study by Zullo et al. six (18%) of 34 CVID patients had overexpression of p53.54 However, in another study, no significant relation was found between TP53 mutation and gastric cancer in CVID patients.79

For many years it has been demonstrated that infection with H. pylori causes chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease which is associated with a two- to nine-fold increased risk of gastric cancer.119–122 Although such a precise study has not been conducted in CVID patients, some gastrointestinal alterations such as decreased production of gastric IgA and hydrochloric acid have been proposed to predispose CVID patients to H. pylori infection that causes more gastric inflammation and increased carcinogenesis.123,124 On the other hand, infection with H. pylori causes chronic gastritis and gastric atrophy that leads to a higher gastric PH and it permits the proliferation of nitrate-reducing anaerobic bacteria which are involved in the pathogenesis of gastric cancers through the generation of carcinogenic N-nitrosamines.125 Considering the high-risk factors for gastric cancer in CVID, periodic screening for H. pylori infection and endoscopic follow-up is recommended for CVID patients.

Breast cancer

Breast cancer is the most common cancer in women worldwide, and second most common cancer overall after lung cancer.126 ASCIA registry in Australia reported a significant increase of breast cancer in female CVID patients with a SIR of 2.24 (95% CI 1.02–4.24), and nine observed cases from more than 400 patients with CVID.17 Similar data was shown in a long-term cohort study of 224 CVID patients, who were followed for a mean time of 11.5 years in Italy. In this cohort, two patients with breast cancer and a Standardised Prevalence Ratio (SPR) of 2.02 (95% CI 0.22–7.29) was reported.127 Finally, in the largest cohort by European Society for Immunodeficiencies, 13 cases of breast tumours were identified among 2212 patients with CVID.128 Immune impairment may also have a role in the development of breast cancer in CVID patients by increasing susceptibility to some infections such as the mouse mammary tumour virus, which has been found in 38% of human breast cancers and shared DNA repair gene defects.15

Thymus cancer

Thymoma is a rare malignancy with unknown aetiology. According to cancer registry data, the overall incidence of thymoma in the U.S. is 0.13 per 100,000 person-years. Thymoma is very uncommon in children and young adults.129 Several studies have suggested that patients with thymoma have an increased risk for other malignancies, especially for developing B-cell non-Hodgkin lymphoma, consistent with an effect of immune disturbance arising from the thymoma or its treatment. Also, patients with thymoma may have an elevated risk of developing soft tissue sarcomas.130,131 Hypogammaglobulinaemia could be associated with 6–11% of thymoma patients mimicking CVID, known as Good's syndrome.132,133 This subgroup of patients potentially suffers from a cell-mediated immune defect due to an increased risk of opportunistic viral infections including herpes simplex virus (HSV), varicella zoster virus (VZV), CMV and HHV8 and autoimmune conditions (myasthenia gravis, pure red cell aplasia and pernicious anaemia).133 An enormous 146-fold increased risk of thymus cancer in CVID patients has been reported in 416 patients in the ASCIA registry.17 In another study, a large excess risk for thymoma was observed on the basis of two thymoma cases occurred in CVID patients.126


The incidence rate of lymphoma in CVID patient is approximately 7–10%, which appears to be higher than in the normal population.34,128 For the first time Kinlen et al.,114 in 1985 reported a 30-fold increase in the risk of lymphoma by performing a prospective study of 220 CVID patients with 11 years’ follow-up. Two years later, Cunningham-Rundles134 reported a 259-fold increase in lymphoma risk. Quinti et al.127 in 2007 reported a 12–18-fold increased incidence of lymphoma development in CVID patients. Despite advances in immunoglobulin replacement, infection surveillance and antibiotic administration, lymphoma remains the most common severe complication of CVID, which can progress even with no prior history or symptoms of lymphoid hyperplasia.135

NHL is the most frequent CVID-associated malignancy and several studies have shown that NHL had estimates ranging from 3 to 8%.5,17,34 In a long-term study, 38 of 416 patients with CVID had malignancy, which NHL represented 29% of the total.17 However, there are much fewer reports of Hodgkin lymphoma in CVID, compared to NHL. In one cohort of 473 patients with CVID, there were only four cases (0.8%) of Hodgkin lymphoma, while 32 patients (6.7%) developed NHL.14

Lymphomas in CVID are usually extranodal, B cell in type, more common in adult patients and are usually EBV-negative.34,136,137 In the US report with 1–25 years’ follow-up of cases, 8.2% of 248 CVID patients had lymphoid malignancies which were all B cell in type. NHL was the most frequent diagnosis,19 with some of these being further classified into specific B-cell phenotypes, including MALT, marginal zone lymphoma, and T cell-rich B-cell EBV-associated lymphoma.33 MALT lymphomas are the most common NHL subtype in CVID patients. In a review of MALT lymphomas, extranodal marginal zone were among the most frequently reported lymphomas.21,54,138 Several other cases of MALT lymphomas, localised in the lung and salivary glands have also been published.11,139,140

There are some proposed risk factors for increased of lymphoma in CVID patients, these include chronic infections (such as HHV8, CMV, EBV and H. pylori), persistent inflammatory autoimmune disease, immune dysregulation and radiosensitivity,11 but their relative contribution and exact mechanism in CVID is still unknown.

Several studies show that defective immune responses may influence susceptibility to lymphoma due to complicated underlying mechanisms. Importantly, the majority of patients with CVID typically have a defective T-cell response to mitogens and microbial antigens141,142 which has been proposed as an explanation for the increased risk of malignancy especially in those with late-onset combined immunodeficiency (LOCID) presenting with CVID-like phenotype. It is reported that 29% of patients with LOCID developed lymphoma versus 4% of patients with CVID without associated T cell defects.143 There is an association between the number of invariant natural killer T (iNKT) cells in CVID patients with the percentage of class-switched memory B cells and propensity to lymphoproliferation.144 Moreover, it has been demonstrated that CVID patients have reduced numbers of T helper-17 (Th17) cells in their circulation.145 According to the role of interleukin 9 (IL-9) in Th17 cells expansion, one can reasonably suppose that decreased number of Th17 cells in CVID patients may lead to an increase in the IL-9 level as a compensatory effect.146 On the contrary, the studies demonstrating effective interventions of IL-9 in causing Hodgkin lymphoma,147 through the potential role of this cytokine as a tumorigenesis factor in growth/proliferative and anti-apoptotic activities on the different transformed cells.148 These findings are consistent with studies showing that IL-9 induces thymic lymphomas in mice, and IL-9 production is associated with the Hodgkin disease and human T-lymphotropic virus type-1 transformed T-cells in human.149

Recently, it has become clear that some genes including HAVCR1, PFTK1 and KIAA0834 play an important role in the development of lymphoma in CVID patients.85 The vast majority of patients with CVID were identified with duplications in a gene for initiation of DNA replication, namely ORC4L, which is related to the B cell lymphoproliferative disorders.150 In addition, there are few studies showing that chromosomal rearrangements of BCL6 were detected in two-thirds of patients with CVID and NHL.83,151 In addition, mutations in BCL6 have been suggested as a genetic marker for explaining the histogenesis of B-cell lymphoproliferation in CVID patients. In one study by Ariatti et al.151 a panel of five CVID-related NHL was used to accurate analysis of histogenetic markers which disclose that somatic hypermutation of IgVH and BCL-6 genes occurred in 5/5 cases and mutations were stable in all cases, with no evidence of ongoing mutation processes. Promoter hypermethylation of O6-methylguanine-DNA-methyltransferase (MGMT), glutathione S-transferase (GST) p1, as well as of death-associated protein (DAP)-kinase, was detected in 2/5, 3/5 and 3/5 CVID related NHL, respectively. Hypermethylation of the MGMT, DAP-kinase and GSTp1 genes occurs at sustained frequencies in CVID-related NHL and may give novel therapeutic targets and prognostic markers for the clinical management of these lymphomas.151 Also, one patient, who had TP53 gene mutations, developed NHL during nine years’ follow-up in the Kilic et al. study in 2012.


Although NHL is the most common haematological malignancy seen in CVID, Myelodysplastic Syndrome (MDS) and acute leukaemia can also be seen in these patients. In 2006 Ayyildiz et al.152 reported an aggressive natural killer cell leukaemia (ANKL) in a woman with CVID. In the recent study Toh et al. in 2015 shown that three CVID patients have been diagnosed with MDS and acute leukaemias. The first case was a 60-year-old male with asymptomatic CVID and acute lymphocytic leukaemia (ALL). The second case was a 78-year-old male with CVID and AIHA. He was diagnosed with high-risk MDS with complex cytogenetics and an RUNX1 mutation. The third case was a 74-year-old male with CVID complicated by pulmonary hypertension, neutropenia, ITP and AIHA which was recently diagnosed with MDS with ASXL1 mutation.153

Prevention, screening, treatment and prognosis of malignancies in CVID

Epidemiological studies have suggested an increased risk of cancers in CVID patients with female gender, cases with higher levels of serum IgM and polyclonal lymphocytic infiltration phenotype.14,154 Furthermore, family histories of neoplasia could be a hint for the presence of genetic predisposing factor (genes involved in DNA repair and cancer immunosurveillance) in a selected group of patients helping towards finding a cause of immunodeficiency and also for implementation of preventive cares.75,155

For prevention of malignancy in CVID, the known vulnerability factors contributed to the development of malignancies should be considered in routine follow-up evaluation including H. pylori screening and eradication; monitoring of overgrowth of nitrosamine-producing bacteria due to hypochlorhydria in cases with autoimmune pernicious anaemia; decreasing unnecessary irradiation particularly in cases with defined chromosomal radiosensitivity.156 In addition to autoimmune and rheumatological disorder, CVID patients suffer from severe respiratory infections, therefore they may frequently undergo medical imaging that exposes them to irradiation. Since these patients might be sensitive to radiation, they should be protected from unnecessary medical techniques that incorporate radiation; substitution with alternative imaging including ultrasonography or magnetic resonance imaging is suggested for these patients.92,157 Beside punctual age-appropriate cancer screening such as gastric cancer (upper endoscopy), cervical cancer (Pap test and HPV tests), colorectal cancer (finding of precancerous polyps by sigmoidoscopy or colonoscopy), breast cancer (clinical breast examinations and mammograms) and lung cancer (yearly screening with low-dose computed tomography), in patients with high risk factors and exposed to oncogenes, screening by complete blood counts (white blood cell counts and differential), histopathological investigation (bone marrow aspiration and persistent enlarged lymph nodes) and endoscopy (for finding mucosal changes) should be considered if it is indicated medically.156

Treatment of malignancies in CVID is similar to routine chemotherapy protocols and surgical modalities for immunocompetent cancerous individuals but there is controversy for the use of radiotherapy due to the lack of an established threshold for radiation-induced aberrations in radiosensitive patients. Adjutant therapy could be considered in a selected group of patients using rituximab (excluding CD20 deficient patients and in patients with activated AKT antiapoptotic survival), rapamycin (in patients with activated PI3K pathway signalling) and haematopoietic stem cell transplantation (in patients associated with impaired T-cell immunity).156,158,159 Of note the dose adjustment for immunoglobulin replacement is necessary during treatment of malignancies (e.g. lymphoma and leukaemia) in patients with CVID due to a secondary cause of hypogammaglobulinemia.160,161

Not surprisingly, several prognostic studies have shown that CVID patients with cancer phenotype (particularly lymphoid malignancy) had the highest mortality rate (relative risk of 5.5 to infections only phenotype patients).7 Death due to malignancy accounts for 5.7–10.2% of mortality causality in different CVID cohorts14,18 and these patients have the overall survival over 15 years of 28% in Iranian patients and over 40 years approximately 36% in an Italian cohort.15,18


Aligned with developing different therapeutic modalities for severe infectious and non-infectious complications of CVID patients and improvement of their life expectancy, neoplasia (particularly lymphoid malignancies in younger patients and gastrointestinal tract malignancies in elder patients) become a major medical concern for treating physicians and clinical immunologists which needs intensive screening evaluations and consequently preventive interventions and timely treatment. Similar to the general population, in CVID patients the cancer risk can be reduced with changes in diet, lifestyle, and finding of precancerous conditions early as well as accurate and timely diagnosis of lymphoproliferative, infectious and autoimmune diseases. Screening for common cancers helps find these diseases at an early stage, when treatment works best. Chemoprevention and avoidance of unnecessary medical radiation are another approach. Protection from cancer-causing bacteria especially H. pylori, and certain viral infections (transforming viruses) by quick medical diagnosis and treatment is also recommended.

Financial and conflict of interest's disclosure

The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Ethical disclosuresConfidentiality of data

The authors declare that no patient data appears in this article.

Right to privacy and informed consent

The authors declare that no patient data appears in this article.

Protection of human subjects and animals in research

The authors declare that no experiments were performed on humans or animals for this investigation.

S. Ahn, C. Cunningham-Rundles.
Role of B cells in common variable immune deficiency.
Exp Rev Clin Immunol, 5 (2009), pp. 557-564
PubMed PMID: 20477641. Pubmed Central PMCID: 2922984. Epub 2010/05/19. eng
M.E. Conley, L.D. Notarangelo, A. Etzioni.
Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies).
Clin Immunol, 93 (1999), pp. 190-197
PubMed PMID: 10600329
G. Azizi, H. Abolhassani, N. Rezaei, A. Aghamohammadi, M.H. Asgardoon, J. Rahnavard, et al.
The use of immunoglobulin therapy in primary immunodeficiency diseases.
Endocr Metab Immune Disord Drug Targets, (2016),
PubMed PMID: 27456825. Epub 2016/07/28. Eng
P. Mohammadinejad, S. Pourhamdi, H. Abolhassani, B. Mirminachi, A. Havaei, S.N. Masoom, et al.
Primary antibody deficiency in a tertiary referral hospital: a 30-year experiment.
J Investig Allergol Clin Immunol, 25 (2015), pp. 416-425
PubMed PMID: 26817138. Epub 2016/01/29. eng
H. Chapel, M. Lucas, M. Lee, J. Bjorkander, D. Webster, B. Grimbacher, et al.
Common variable immunodeficiency disorders: division into distinct clinical phenotypes.
PubMed PMID: 18319398
H. Chapel, M. Lucas, S. Patel, M. Lee, C. Cunningham-Rundles, E. Resnick, et al.
Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts.
J Allergy Clin Immunol, 130 (2012),
1197-8 e9. PubMed PMID: 22819511. Epub 2012/07/24. eng
H. Chapel, C. Cunningham-Rundles.
Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions.
Br J Haematol, 145 (2009), pp. 709-727
PubMed PMID: 19344423. Pubmed Central PMCID: 2718064. Epub 2009/04/07. eng
A. Aghamohammadi, N. Rezaei, M. Gharagozlou, A. Ramyar, F. Mahjoub, K. Rezaei-Kalantari, et al.
Hodgkin lymphoma in two siblings with common variable immunodeficiency.
Pediatr Hematol Oncol, 24 (2007), pp. 337-342
PubMed PMID: 17613878. Epub 2007/07/07. eng
M.M. Gompels, E. Hodges, R.J. Lock, B. Angus, H. White, A. Larkin, et al.
Lymphoproliferative disease in antibody deficiency: a multi-centre study.
Clin Exp Immunol, 134 (2003), pp. 314-320
PubMed PMID: 14616793. Pubmed Central PMCID: 1808874. Epub 2003/11/18. eng
I. Quinti, A. Soresina, G. Spadaro, S. Martino, S. Donnanno, C. Agostini, et al.
Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency.
J Clin Immunol, 27 (2007), pp. 308-316
PubMed PMID: 17510807. Epub 2007/05/19. eng
C. Cunningham-Rundles, D.L. Cooper, T.P. Duffy, J. Strauchen.
Lymphomas of mucosal-associated lymphoid tissue in common variable immunodeficiency.
Am J Hematol, 69 (2002), pp. 171-178
PubMed PMID: 11891803. Epub 2002/03/14. eng
L. Mellemkjaer, L. Hammarstrom, V. Andersen, J. Yuen, C. Heilmann, T. Barington, et al.
Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study.
Clin Exp Immunol, 130 (2002), pp. 495-500
PubMed PMID: 12452841. Pubmed Central PMCID: 1906562. Epub 2002/11/28. eng
P. Mohammadinejad, A. Aghamohammadi, H. Abolhassani, M.S. Sadaghiani, S. Abdollahzade, B. Sadeghi, et al.
Pediatric patients with common variable immunodeficiency: long-term follow-up.
J Investig Allergol Clin Immunol, 22 (2012), pp. 208-214
PubMed PMID: 22697011. Epub 2012/06/16. eng
E.S. Resnick, E.L. Moshier, J.H. Godbold, C. Cunningham-Rundles.
Morbidity and mortality in common variable immune deficiency over 4 decades.
Blood, 119 (2012), pp. 1650-1657
PubMed PMID: 22180439. Pubmed Central PMCID: 3286343. Epub 2011/12/20. eng
H. Abolhassani, A. Aghamohammadi, A. Imanzadeh, P. Mohammadinejad, B. Sadeghi, N. Rezaei.
Malignancy phenotype in common variable immunodeficiency.
J Investig Allergol Clin Immunol, 22 (2012), pp. 133-134
PubMed PMID: 22533236. Epub 2012/04/27. eng
N. Rezaei, M. Hedayat, A. Aghamohammadi, K.E. Nichols.
Primary immunodeficiency diseases associated with increased susceptibility to viral infections and malignancies.
J Allergy Clin Immunol, 127 (2011),
1329–41 e2; quiz 42-3. PubMed PMID: 21514636. Epub 2011/04/26. eng
C.M. Vajdic, L. Mao, M.T. van Leeuwen, P. Kirkpatrick, A.E. Grulich, S. Riminton.
Are antibody deficiency disorders associated with a narrower range of cancers than other forms of immunodeficiency?.
Blood, 116 (2010), pp. 1228-1234
PubMed PMID: 20466855. Epub 2010/05/15. eng.
I. Quinti, C. Agostini, S. Tabolli, G. Brunetti, F. Cinetto, A. Pecoraro, et al.
Malignancies are the major cause of death in patients with adult onset common variable immunodeficiency.
Blood, 120 (2012), pp. 1953-1954
PubMed PMID: 22936739. Epub 2012/09/01. eng
M. Piquer Gibert, L. Alsina, M.T. Giner Munoz, O. Cruz Martinez, K. Ruiz Echevarria, O. Dominguez, et al.
Non-Hodgkin lymphoma in pediatric patients with common variable immunodeficiency.
Eur J Pediatr, 174 (2015), pp. 1069-1076
PubMed PMID: 25749928. Epub 2015/03/10. eng
E. Lopez-Rocha, K. Rodriguez-Mireles, N.H. Segura-Mendez, M.A. Yamazaki-Nakashimada.
Malignancies in adult patients with common variable immunodeficiency.
Rev Alerg Mex, 62 (2015), pp. 22-27
PubMed PMID: 25758110. Epub 2015/03/12. Prevalencia de cancer en pacientes adultos con inmunodeficiencia comun variable. spa
I.M. Desar, M. Keuter, J.M. Raemaekers, J.B. Jansen, J.H. van Krieken, J.W. van der Meer.
Extranodal marginal zone (MALT) lymphoma in common variable immunodeficiency.
Neth J Med, 64 (2006), pp. 136-140
PubMed PMID: 16702611. Epub 2006/05/17. eng
F. Dhalla, S.P. da Silva, M. Lucas, S. Travis, H. Chapel.
Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programme.
Clin Exp Immunol, 165 (2011), pp. 1-7
PubMed PMID: 21470209. Pubmed Central PMCID: 3110315. Epub 2011/04/08. eng
G. De Petris, B.M. Dhungel, L. Chen, Y.H. Chang.
Gastric adenocarcinoma in common variable immunodeficiency: features of cancer and associated gastritis may be characteristic of the condition.
Int J Surg Pathol, 22 (2014), pp. 600-606
PubMed PMID: 24788529. Epub 2014/05/03. eng
C. Cunningham-Rundles.
The many faces of common variable immunodeficiency.
Hematol Am Soc Hematol Educ Program, 2012 (2012), pp. 301-305
PubMed PMID: 23233596. Pubmed Central PMCID: 4066657. Epub 2012/12/13. eng
D. Martin, J.S. Gutkind.
Human tumor-associated viruses and new insights into the molecular mechanisms of cancer.
Oncogene, 27 (2008), pp. S31-S42
PubMed PMID: 19956178. Epub 2009/12/04. eng
M. Philip, D.A. Rowley, H. Schreiber.
Inflammation as a tumor promoter in cancer induction.
Semin Cancer Biol, 14 (2004), pp. 433-439
PubMed PMID: 15489136. Epub 2004/10/19. eng
J. Bartkova, Z. Horejsi, K. Koed, A. Kramer, F. Tort, K. Zieger, et al.
DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis.
Nature, 434 (2005), pp. 864-870
PubMed PMID: 15829956. Epub 2005/04/15. eng
C. Watkins, R. Sahni, N. Holla, J. Litchfield, G. Youngberg, G. Krishnaswamy.
Malignancy in common variable immune deficiency: report of two rare cases of gastrointestinal malignancy and a review of the literature.
Cardiovasc Hematol Disord Drug Targets, 12 (2012), pp. 21-27
PubMed PMID: 22746346. Epub 2012/07/04. eng
R. Yazdani, M. Fatholahi, M. Ganjalikhani-Hakemi, H. Abolhassani, G. Azizi, K.M. Hamid, et al.
Role of apoptosis in common variable immunodeficiency and selective immunoglobulin A deficiency.
PubMed PMID: 26795881. Epub 2016/01/23. eng
F.H. Igney, P.H. Krammer.
Immune escape of tumors: apoptosis resistance and tumor counterattack.
J Leukoc Biol, 71 (2002), pp. 907-920
PubMed PMID: 12050175. Epub 2002/06/07. eng
M.J. Smyth, D.I. Godfrey, J.A. Trapani.
A fresh look at tumor immunosurveillance and immunotherapy.
Nat Immunol, 2 (2001), pp. 293-299
PubMed PMID: 11276199. Epub 2001/03/29. eng
E. Vivier, S. Ugolini, D. Blaise, C. Chabannon, L. Brossay.
Targeting natural killer cells and natural killer T cells in cancer.
Nat Rev Immunol, 12 (2012), pp. 239-252
PubMed PMID: 22437937. Epub 2012/03/23. eng
S. Gangemi, A. Allegra, C. Musolino.
Lymphoproliferative disease and cancer among patients with common variable immunodeficiency.
Leuk Res, 39 (2015), pp. 389-396
PubMed PMID: 25711943. Epub 2015/02/26. eng
C. Cunningham-Rundles, C. Bodian.
Common variable immunodeficiency: clinical and immunological features of 248 patients.
Clin Immunol, 92 (1999), pp. 34-48
PubMed PMID: 10413651. Epub 1999/07/22. eng
A. Aghamohammadi, A. Farhoudi, M. Moin, N. Rezaei, A. Kouhi, Z. Pourpak, et al.
Clinical and immunological features of 65 Iranian patients with common variable immunodeficiency.
Clin Diagn Lab Immunol, 12 (2005), pp. 825-832
PubMed PMID: 16002630. Pubmed Central PMCID: 1182213. Epub 2005/07/09. eng
R.M. Aspalter, W.A. Sewell, K. Dolman, J. Farrant, A.D. Webster.
Deficiency in circulating natural killer (NK) cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia.
Clin Exp Immunol, 121 (2000), pp. 506-514
PubMed PMID: 10971518. Pubmed Central PMCID: 1905722. Epub 2000/09/06. eng
A. Chandra, F. Zhang, K.C. Gilmour, D. Webster, V. Plagnol, D.S. Kumararatne, et al.
Common variable immunodeficiency and natural killer cell lymphopenia caused by Ets-binding site mutation in the IL-2 receptor gamma (IL2RG) gene promoter.
J Allergy Clin Immunol, 137 (2016),
940-2 e4. PubMed PMID: 26525228. Pubmed Central PMCID: 4774944
J. Brent, D. Guzman, C. Bangs, B. Grimbacher, C. Fayolle, A. Huissoon, et al.
Clinical and laboratory correlates of lung disease and cancer in adults with idiopathic hypogammaglobulinaemia.
Clin Exp Immunol, 184 (2016), pp. 73-82
PubMed PMID: 26646609. Pubmed Central PMCID: 4778100
A.L. Franks, J.E. Slansky.
Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases and cancer.
Anticancer Res, 32 (2012), pp. 1119-1136
PubMed PMID: 22493341. Pubmed Central PMCID: 3349285
K.E. Smedby, H. Hjalgrim, J. Askling, E.T. Chang, H. Gregersen, A. Porwit-MacDonald, et al.
Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype.
J Natl Cancer Inst, 98 (2006), pp. 51-60
PubMed PMID: 16391371
H. Abolhassani, D. Amirkashani, N. Parvaneh, P. Mohammadinejad, B. Gharib, S. Shahinpour, et al.
Autoimmune phenotype in patients with common variable immunodeficiency.
J Investig Allergol Clin Immunol, 23 (2013), pp. 323-329
PubMed PMID: 24260977
G. Azizi, A. Ghanavatinejad, H. Abolhassani, R. Yazdani, N. Rezaei, A. Mirshafiey, et al.
Autoimmunity in primary T-cell immunodeficiencies.
Exp Rev Clin Immunol, 28 (2016), pp. 1-18
PubMed PMID: 27063703
W.B. Morrison.
Inflammation and cancer: a comparative view.
J Vet Intern Med, 26 (2012), pp. 18-31
PubMed PMID: 22151229. Epub 2011/12/14. eng
S. Rajput, A. Wilber.
Roles of inflammation in cancer initiation, progression, and metastasis.
Front Biosci (Schol Ed), 2 (2010), pp. 176-183
PubMed PMID: 20036938. Epub 2009/12/29. eng
Infections that can lead to cancer [Internet]. American Cancer Society. 2014 [cited 9/24/2014]. Available from: http://www.cancer.org/cancer/cancercauses/othercarcinogens/infectiousagents/infectiousagentsandcancer/infectious-agents-and-cancer-toc.
D.W. Kamp, E. Shacter, S.A. Weitzman.
Chronic inflammation and cancer: the role of the mitochondria.
Oncology (Williston Park), 25 (2011), pp. 400-410
PubMed PMID: 21710835. Epub 2011/06/30. eng
D.E. Griffin.
Measles virus-induced suppression of immune responses.
Immunol Rev, 236 (2010), pp. 176-189
PubMed PMID: 20636817. Pubmed Central PMCID: 2908915. Epub 2010/07/20. eng
P. Borrow, C.F. Evans, M.B. Oldstone.
Virus-induced immunosuppression: immune system-mediated destruction of virus-infected dendritic cells results in generalized immune suppression.
J Virol, 69 (1995), pp. 1059-1070
PubMed PMID: 7815484. Pubmed Central PMCID: 188677. Epub 1995/02/01. eng
P. Correa.
Helicobacter pylori as a pathogen and carcinogen.
J Physiol Pharmacol, 48 (1997), pp. 19-24
PubMed PMID: 9440052. Epub 1998/01/24. eng
S.E. Erdman, P. Correa, L.A. Coleman, M.D. Schrenzel, X. Li, J.G. Fox.
Helicobacter mustelae-associated gastric MALT lymphoma in ferrets.
Am J Pathol, 151 (1997), pp. 273-280
PubMed PMID: 9212752. Pubmed Central PMCID: 1857920. Epub 1997/07/01. eng
P. Correa, M.B. Piazuelo.
Evolutionary history of the Helicobacter pylori genome: implications for gastric carcinogenesis.
Gut Liver, 6 (2012), pp. 21-28
PubMed PMID: 22375167. Pubmed Central PMCID: 3286735. Epub 2012/03/01. eng
R. Chaturvedi, T. de Sablet, M. Asim, M.B. Piazuelo, D.P. Barry, T.G. Verriere, et al.
Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase.
Oncogene, 34 (2015), pp. 3429-3440
PubMed PMID: 25174398. Pubmed Central PMCID: 4345146. Epub 2014/09/02. eng
P. Wood, S. Stanworth, J. Burton, A. Jones, D.G. Peckham, T. Green, et al.
Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review.
Clin Exp Immunol, 149 (2007), pp. 410-423
PubMed PMID: 17565605. Pubmed Central PMCID: 2219316. Epub 2007/06/15. eng
A. Zullo, A. Romiti, V. Rinaldi, A. Vecchione, S. Tomao, F. Aiuti, et al.
Gastric pathology in patients with common variable immunodeficiency.
Gut, 45 (1999), pp. 77-81
PubMed PMID: 10369708. Pubmed Central PMCID: 1727591. Epub 1999/06/16. eng
I. Chua, I. Quinti, B. Grimbacher.
Lymphoma in common variable immunodeficiency: interplay between immune dysregulation, infection and genetics.
Curr Opin Hematol, 15 (2008), pp. 368-374
PubMed PMID: 18536576. Epub 2008/06/10. eng
S.F. Moss, P. Malfertheiner.
Helicobacter and gastric malignancies.
Helicobacter, 12 (2007), pp. 23-30
PubMed PMID: 17727457. Epub 2007/10/11. eng
I.M. Desar, M. van Deuren, T. Sprong, J.B. Jansen, F. Namavar, C.M. Vandenbroucke-Grauls, et al.
Serum bactericidal activity against Helicobacter pylori in patients with hypogammaglobulinaemia.
Clin Exp Immunol, 156 (2009), pp. 434-439
PubMed PMID: 19438595. Pubmed Central PMCID: 2691971. Epub 2009/05/15. eng
C. Seeger, W.S. Mason.
Molecular biology of hepatitis B virus infection.
Virology, 479–480 (2015), pp. 672-686
PubMed PMID: 25759099. Pubmed Central PMCID: 4424072. Epub 2015/03/12. eng
Y. Cao, J. Chen, D. Wang, H. Peng, X. Tan, D. Xiong, et al.
Upregulated in Hepatitis B virus-associated hepatocellular carcinoma cells, miR-331-3p promotes proliferation of hepatocellular carcinoma cells by targeting ING5.
Oncotarget, (2015),
PubMed PMID: 26497554. Epub 2015/10/27. Eng
K. Gandhi, P. Parikh, W.S. Aronow, H. Desai, H. Amin, M. Sharma, et al.
A case of explosive progression of hepatocellular carcinoma in a patient with common variable immunodeficiency (CVID).
J Gastrointest Cancer, 41 (2010), pp. 281-284
PubMed PMID: 20473587. Epub 2010/05/18. eng
Y. Murakawa, A. Miyagawa-Hayashino, Y. Ogura, H. Egawa, S. Okamoto, Y. Soejima, et al.
Liver transplantation for severe hepatitis in patients with common variable immunodeficiency.
Pediatr Transpl, 16 (2012), pp. E210-E216
PubMed PMID: 21831259. Epub 2011/08/13. eng
K. Fukushima, Y. Ueno, H. Kanegane, Y. Yamagiwa, J. Inoue, O. Kido, et al.
A case of severe recurrent hepatitis with common variable immunodeficiency.
Hepatol Res, 38 (2008), pp. 415-420
PubMed PMID: 18021227. Epub 2007/11/21. eng
C. Copie-Bergman, G. Niedobitek, D.C. Mangham, J. Selves, K. Baloch, T.C. Diss, et al.
Epstein-Barr virus in B-cell lymphomas associated with chronic suppurative inflammation.
PubMed PMID: 9422983. Epub 1998/01/10. eng
P. German, Z. Beck, I. Semsei, S. Kiss, B. Gorog, E. Balogh, et al.
Study of pathogenetic role of Epstein-Barr virus in Hungarian patients with B-cell non-Hodgkin lymphomas.
Orv Hetil, 143 (2002), pp. 2619-2624
PubMed PMID: 12532647. Epub 2003/01/21. Az Epstein-Barr virus patogenetikai szerepenek tanulmanyozasa magyarorszagi B-sejtes non-Hodgkin lymphomas betegekben. hun
G. Brady, G.J. MacArthur, P.J. Farrell.
Epstein-Barr virus and Burkitt lymphoma.
J Clin Pathol, 60 (2007), pp. 1397-1402
PubMed PMID: 18042696. Pubmed Central PMCID: 2095571. Epub 2007/11/29. eng
J. Bornstein, M.A. Rahat, H. Abramovici.
Etiology of cervical cancer: current concepts.
Obstet Gynecol Surv, 50 (1995), pp. 146-154
PubMed PMID: 7731627. Epub 1995/02/01. eng
A. Abudoukadeer, M. Niyazi, A. Aikula, M. Kamilijian, X. Sulaiman, A. Mutailipu, et al.
Association of EBV and HPV co-infection with the development of cervical cancer in ethnic Uyghur women.
Eur J Gynaecol Oncol, 36 (2015), pp. 546-550
PubMed PMID: 26513880. Epub 2015/10/31. eng
Y. Chang, E. Cesarman, M.S. Pessin, F. Lee, J. Culpepper, D.M. Knowles, et al.
Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma.
Science, 266 (1994), pp. 1865-1869
PubMed PMID: 7997879. Epub 1994/12/16. eng
G. Zuccaro, S. Della Bella, B. Polizzi, M. Vanoli, R. Scorza.
Common variable immunodeficiency following Epstein-Barr virus infection.
J Clin Lab Immunol, 49 (1997), pp. 41-45
PubMed PMID: 9819672. Epub 1997/01/01. eng
W.H. Wheat, C.D. Cool, Y. Morimoto, P.R. Rai, C.H. Kirkpatrick, B.A. Lindenbaum, et al.
Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency.
J Exp Med, 202 (2005), pp. 479-484
PubMed PMID: 16103407. Pubmed Central PMCID: 2212861. Epub 2005/08/17. eng
J. Vu, G.R. Wallace, R. Singh, H. Diwan, V. Prieto, P. Rady, et al.
Common variable immunodeficiency syndrome associated with epidermodysplasia verruciformis.
Am J Clin Dermatol, 8 (2007), pp. 307-310
PubMed PMID: 17902733. Epub 2007/10/02. eng
P. Kralickova, E. Mala, D. Vokurkova, I. Krcmova, L. Pliskova, V. Stepanova, et al.
Cytomegalovirus disease in patients with common variable immunodeficiency: three case reports.
Int Arch Allergy Immunol, 163 (2014), pp. 69-74
PubMed PMID: 24247002. Epub 2013/11/20. eng
T. Witte, S. Werwitzke, R.E. Schmidt.
CMV complications in common variable immunodeficiency.
Immunobiology, 202 (2000), pp. 194-198
PubMed PMID: 10993294. Epub 2000/09/19. eng
L. Koochakzadeh, S. Hosseinverdi, M. Hedayat, F. Farahani, A. Tofighi, M. Eghbali, et al.
Study of SH2D1A gene mutation in paediatric patients with B-cell lymphoma.
Allergol Immunopathol (Madr), 43 (2015), pp. 568-570
PubMed PMID: 25982576. Epub 2015/05/20. eng
O.K. Alkhairy, R. Perez-Becker, G.J. Driessen, H. Abolhassani, J. van Montfrans, S. Borte, et al.
Novel mutations in TNFRSF7/CD27: clinical, immunologic, and genetic characterization of human CD27 deficiency.
J Allergy Clin Immunol, 136 (2015),
703-12 e10. PubMed PMID: 25843314. Epub 2015/04/07. eng
C. Oliveira, P. Ferreira, S. Nabais, L. Campos, A. Ferreira, L. Cirnes, et al.
E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients.
Eur J Cancer, 40 (2004), pp. 1897-1903
PubMed PMID: 15288293. Epub 2004/08/04. eng
H. Yamada, K. Shinmura, K. Okudela, M. Goto, M. Suzuki, K. Kuriki, et al.
Identification and characterization of a novel germ line p53 mutation in familial gastric cancer in the Japanese population.
Carcinogenesis, 28 (2007), pp. 2013-2018
PubMed PMID: 17690113. Epub 2007/08/11. eng
G. Keller, V. Grimm, H. Vogelsang, P. Bischoff, J. Mueller, J.R. Siewert, et al.
Analysis for microsatellite instability and mutations of the DNA mismatch repair gene hMLH1 in familial gastric cancer.
PubMed PMID: 8938136. Epub 1996/11/27. eng
S.S. Kilic.
The p53 status in patients with common variable immunodeficiency.
J Clin Med Res, 4 (2012), pp. 44-47
R. Lai, D.A. Arber, K.L. Chang, C.S. Wilson, L.M. Weiss.
Frequency of bcl-2 expression in non-Hodgkin's lymphoma: a study of 778 cases with comparison of marginal zone lymphoma and monocytoid B-cell hyperplasia.
Mod Pathol, 11 (1998), pp. 864-869
PubMed PMID: 9758366. Epub 1998/10/03. eng
S.D. Wagner, M. Ahearne, P. Ko Ferrigno.
The role of BCL6 in lymphomas and routes to therapy.
Br J Haematol, 152 (2011), pp. 3-12
PubMed PMID: 21083654. Epub 2010/11/19. eng
J.R. Cerhan, W. Liu-Mares, Z.S. Fredericksen, A.J. Novak, J.M. Cunningham, N.E. Kay, et al.
Genetic variation in tumor necrosis factor and the nuclear factor-kappaB canonical pathway and risk of non-Hodgkin's lymphoma.
Cancer Epidemiol Biomarkers Prev, 17 (2008), pp. 3161-3169
PubMed PMID: 18990758. Pubmed Central PMCID: 2735864. Epub 2008/11/08. eng
C. Ariatti, D. Vivenza, D. Capello, A. Migliazza, G. Parvis, L. Fassone, et al.
Common-variable immunodeficiency-related lymphomas associate with mutations and rearrangements of BCL-6: pathogenetic and histogenetic implications.
Hum Pathol, 31 (2000), pp. 871-873
PubMed PMID: 10923927. Epub 2000/08/03. eng
M. Fliegauf, V.L. Bryant, N. Frede, C. Slade, S.T. Woon, K. Lehnert, et al.
Haploinsufficiency of the NF-kappaB1 Subunit p50 in common variable immunodeficiency.
Am J Hum Genet, 97 (2015), pp. 389-403
PubMed PMID: 26279205. Pubmed Central PMCID: 4564940. Epub 2015/08/19. eng
J.S. Orange, J.T. Glessner, E. Resnick, K.E. Sullivan, M. Lucas, B. Ferry, et al.
Genome-wide association identifies diverse causes of common variable immunodeficiency.
J Allergy Clin Immunol, 127 (2011),
1360-7 e6. PubMed PMID: 21497890. Pubmed Central PMCID: 3646656. Epub 2011/04/19. eng
S.S. Wang, C.M. Vajdic, M.S. Linet, S.L. Slager, J. Voutsinas, A. Nieters, et al.
Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci.
Am J Epidemiol, 181 (2015), pp. 406-421
PubMed PMID: 25713336. Pubmed Central PMCID: 4402340. Epub 2015/02/26. eng
L. Varoczy, E. Payer, Z. Kadar, L. Gergely, Z. Miltenyi, F. Magyari, et al.
Malignant lymphomas and autoimmunity-a single center experience from Hungary.
Clin Rheumatol, 31 (2012), pp. 219-224
PubMed PMID: 21735057. Epub 2011/07/08. eng
E. Maverakis, H. Goodarzi, L.N. Wehrli, Y. Ono, M.S. Garcia.
The etiology of paraneoplastic autoimmunity.
Clin Rev Allergy Immunol, 42 (2012), pp. 135-144
PubMed PMID: 21246308. Epub 2011/01/20. eng
J. Wang, C. Cunningham-Rundles.
Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID).
J Autoimmun, 25 (2005), pp. 57-62
PubMed PMID: 15994061. Epub 2005/07/05. eng
A.W. Hauswirth, C. Skrabs, C. Schutzinger, M. Raderer, A. Chott, P. Valent, et al.
Autoimmune thrombocytopenia in non-Hodgkin's lymphomas.
Haematologica, 93 (2008), pp. 447-450
PubMed PMID: 18287133. Epub 2008/02/22. eng
P.M. Oifarrill-Romanillos, F.H. Campos-Romero, L.D. Mendoza-Reyna, A.S. Amaya-Mejia, L.V. Galindo-Pacheco, B. Gonzalez-Virla, et al.
[Autoimmune hematologic diseases in adult patients with common variable immunodeficiency].
Rev Alerg Mex, 59 (2012), pp. 187-191
PubMed PMID: 24008027. Epub 2013/09/07. Enfermedades hematologicas autoinmunes en adultos con inmunodeficiencia com n variable. spa
G. Azizi, H. Abolhassani, M.H. Asgardoon, T. Alinia, R. Yazdani, J. Mohammadi, et al.
Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management.
Exp Rev Clin Immunol, 16 (2016), pp. 1-15
PubMed PMID: 27636680. Epub 2016/09/17. Eng
G. Azizi, M.R. Pouyani, H. Abolhassani, L. Sharifi, M.Z. Dizaji, J. Mohammadi, et al.
Cellular and molecular mechanisms of immune dysregulation and autoimmunity.
Cell Immunol, (2016 Aug 27),
PubMed PMID: 27614846. Epub 2016/09/12. Eng
I. Vorechovsky, M. Munzarova, J. Lokaj.
Increased bleomycin-induced chromosome damage in lymphocytes of patients with common variable immunodeficiency indicates an involvement of chromosomal instability in their cancer predisposition.
Cancer Immunol Immunotherapy, 29 (1989), pp. 303-306
PubMed PMID: 2473834
I. Vorechovsky, J. Litzman, J. Lokaj, P. Hausner, T. Poch.
Common variable immunodeficiency and malignancy: a report of two cases and possible explanation for the association.
Cancer Immunol Immunotherapy, 31 (1990), pp. 250-254
PubMed PMID: 2379221
R. Gantt, R. Parshad, F.M. Price, K.K. Sanford.
Biochemical evidence for deficient DNA repair leading to enhanced G2 chromatid radiosensitivity and susceptibility to cancer.
Radiation Res, 108 (1986), pp. 117-126
A.R. Gennery, A.J. Cant, P.A. Jeggo.
Immunodeficiency associated with DNA repair defects.
Clin Exp Immunol, 121 (2000), pp. 1-7
PubMed PMID: 10886231. Pubmed Central PMCID: 1905662. Epub 2000/07/11. eng
A. Aghamohammadi, M. Moin, A. Kouhi, M.A. Mohagheghi, A. Shirazi, N. Rezaei, et al.
Chromosomal radiosensitivity in patients with common variable immunodeficiency.
Immunobiology, 213 (2008), pp. 447-454
PubMed PMID: 18472053
I. Vorechovsky, D. Scott, M.R. Haeney, D.A. Webster.
Chromosomal radiosensitivity in common variable immune deficiency.
Mutation Res, 290 (1993), pp. 255-264
PubMed PMID: 7694117. Epub 1993/12/01. eng
S. Palanduz, A. Palanduz, I. Yalchin.
In vitro chromosomal radiosensitivity in common variable immunodeficiency.
Clin Immunol Immunopathol, 86 (1998), pp. 180-182
S.M. Offer, Q. Pan-Hammarström, L. Hammarström, R.S. Harris.
Unique DNA repair gene variations and potential associations with the primary antibody deficiency syndromes IgAD and CVID.
S. Palanduz, A. Palanduz, I. Yalcin, A. Somer, U. Ones, D. Ustek, et al.
In vitro chromosomal radiosensitivity in common variable immune deficiency.
Clin Immunol Immunopathol, 86 (1998), pp. 180-182
PubMed PMID: 9473380. Epub 1998/03/07. eng
M.R. Lieber.
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway.
Annu Rev Biochem, 79 (2010), pp. 181-211
PubMed PMID: 20192759. Pubmed Central PMCID: 3079308. Epub 2010/03/03. eng
M.L. Hefferin, A.E. Tomkinson.
Mechanism of DNA double-strand break repair by non-homologous end joining.
DNA Repair (Amst), 4 (2005), pp. 639-648
PubMed PMID: 15907771. Epub 2005/05/24. eng
P.A. van Schouwenburg, E.E. Davenport, A.K. Kienzler, I. Marwah, B. Wright, M. Lucas, et al.
Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.
Clin Immunol, 160 (2015), pp. 301-314
PubMed PMID: 26122175. Pubmed Central PMCID: 4601528. Epub 2015/07/01. eng
C. Anzilotti, A.K. Kienzler, E. Lopez-Granados, S. Gooding, B. Davies, H. Pandit, et al.
Key stages of bone marrow B-cell maturation are defective in patients with common variable immunodeficiency disorders.
J Allergy Clin Immunol, 136 (2015),
487-90 e2. PubMed PMID: 25725990. Epub 2015/03/03. eng
B. Duvvuri, V.R. Duvvuri, J. Grigull, A. Martin, Q. Pan-Hammarstrom, G.E. Wu, et al.
Altered spectrum of somatic hypermutation in common variable immunodeficiency disease characteristic of defective repair of mutations.
Immunogenetics, 63 (2011), pp. 1-11
PubMed PMID: 20938659. Epub 2010/10/13. eng
H. Sekine, R.C. Ferreira, Q. Pan-Hammarstrom, R.R. Graham, B. Ziemba, S.S. de Vries, et al.
Role for Msh5 in the regulation of Ig class switch recombination.
Proc Natl Acad Sci U S A, 104 (2007), pp. 7193-7198
PubMed PMID: 17409188. Pubmed Central PMCID: 1855370. Epub 2007/04/06. eng
S. Nemati, A.A. Amirzargar, E. Farhadi, A. Hirbod-Mobarakeh, M. Nabavi, S. Soltani, et al.
RAD50 single-nucleotide polymorphism in predominantly antibody deficiency.
J Investig Allergol Clin Immunol, 25 (2015), pp. 299-301
PubMed PMID: 26310047. Epub 2015/08/28. eng
L. Ohm-Laursen, L. Schjebel, K. Jacobsen, H. Permin, A. Svejgaard, T. Barington.
Normal ICOS, ICOSL and AID alleles in Danish patients with common variable immunodeficiency.
Scand J Immunol, 61 (2005), pp. 566-574
PubMed PMID: 15963052. Epub 2005/06/21. eng
D.M. Parkin, F. Bray, J. Ferlay, P. Pisani.
Global cancer statistics, 2002.
CA: Cancer J Clin, 55 (2005), pp. 74-108
PubMed PMID: 15761078
World Cancer Report.
International agency for research on cancer.
World Health Organization, (2014),
ISBN 978-92-832-0432-9
American Cancer Society.
Cancer facts and figures 2016.
American Cancer Society, (2016),
L.J. Kinlen, A.D. Webster, A.G. Bird, R. Haile, J. Peto, J.F. Soothill, et al.
Prospective study of cancer in patients with hypogammaglobulinaemia.
PubMed PMID: 2857327
F.A. Bonilla, I.L. Bernstein, D.A. Khan, Z.K. Ballas, J. Chinen, M.M. Frank, et al.
Practice parameter for the diagnosis and management of primary immunodeficiency.
Annals Allergy Asthma Immunol: Off Publ Am College Allergy Asthma Immunol, 94 (2005), pp. S1-S63
PubMed PMID: 15945566
K.D. Crew, A.I. Neugut.
Epidemiology of gastric cancer.
World J Gastroenterol, 12 (2006), pp. 354-362
PubMed PMID: 16489633. Pubmed Central PMCID: 4066052
F. Berrino, G. Gatta, M. Sant, R. Capocaccia.
The EUROCARE study of survival of cancer patients in Europe: aims, current status, strengths and weaknesses.
Eur J Cancer, 37 (2001), pp. 673-677
PubMed PMID: 11311640
P.F. Yong, M. Tarzi, I. Chua, B. Grimbacher, R. Chee.
Common variable immunodeficiency: an update on etiology and management.
Immunol Allergy Clin North Am, 28 (2008), pp. 367-386
ix-x. PubMed PMID: 18424338
L.E. Wroblewski, R.M. Peek Jr., K.T. Wilson.
Helicobacter pylori and gastric cancer: factors that modulate disease risk.
Clin Microbio Rev, 23 (2010), pp. 713-739
PubMed PMID: 20930071. Pubmed Central PMCID: 2952980
F. Wang, W. Meng, B. Wang, L. Qiao.
Helicobacter pylori-induced gastric inflammation and gastric cancer.
Cancer Lett, 345 (2014), pp. 196-202
PubMed PMID: 23981572
D. Forman, P. Webb, J. Parsonnet.
H. pylori and gastric cancer.
Lancet, 343 (1994), pp. 243-244
PubMed PMID: 7904707
J. Danesh.
Helicobacter pylori infection and gastric cancer: systematic review of the epidemiological studies.
Alimentary Pharmacol Therapeut, 13 (1999), pp. 851-856
PubMed PMID: 10383517
A.K. Bogstedt, S. Nava, T. Wadstrom, L. Hammarstrom.
Helicobacter pylori infections in IgA deficiency: lack of role for the secretory immune system.
Clin Exp Immunol, 105 (1996), pp. 202-204
PubMed PMID: 8706322. Pubmed Central PMCID: 2200521
M. Quiding-Jarbrink, P. Sundstrom, A. Lundgren, M. Hansson, M. Backstrom, C. Johansson, et al.
Decreased IgA antibody production in the stomach of gastric adenocarcinoma patients.
Clin Immunol, 131 (2009), pp. 463-471
PubMed PMID: 19249247
P. Sipponen, M. Kekki, K. Seppala, M. Siurala.
The relationships between chronic gastritis and gastric acid secretion.
Alimentary Pharmac Therapeutics, 10 (1996 Apr), pp. 103-118
PubMed PMID: 8730265
P.E. Tarr, M.C. Sneller, L.J. Mechanic, A. Economides, C.M. Eger, W. Strober, et al.
Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature.
Medicine (Baltimore), 80 (2001), pp. 123-133
PubMed PMID: 11307588
I. Quinti, A. Soresina, G. Spadaro, S. Martino, S. Donnanno, C. Agostini, et al.
Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency.
J Clin Immunol, 27 (2007), pp. 308-316
PubMed PMID: 17510807
B. Gathmann, N. Mahlaoui, Ceredih, L. Gerard, E. Oksenhendler, K. Warnatz, et al.
Clinical picture and treatment of 2212 patients with common variable immunodeficiency.
J Allergy Clin Immunol, 134 (2014), pp. 116-126
PubMed PMID: 24582312.
E.A. Engels.
Epidemiology of thymoma and associated malignancies.
J Thoracic Oncology: Off Publ Int Assoc Study Lung Cancer, 5 (2010), pp. S260-S265
PubMed PMID: 20859116. Pubmed Central PMCID: 2951303
H. Sarner.
When death necessitates selling a practice.
CAL [magazine] Certified Akers Laboratories, 39 (1976), pp. 2-4
PubMed PMID: 1070377
C.C. Pan, P.C. Chen, L.S. Wang, K.H. Chi, H. Chiang.
Thymoma is associated with an increased risk of second malignancy.
Cancer, 92 (2001), pp. 2406-2411
PubMed PMID: 11745297
J.V. Souadjian, P. Enriquez, M.N. Silverstein, J.M. Pepin.
The spectrum of diseases associated with thymoma. Coincidence or syndrome?.
Arch Intern Med, 134 (1974), pp. 374-379
PubMed PMID: 4602050. Epub 1974/08/01. eng
P. Kelleher, S.A. Misbah.
What is Good's syndrome?. Immunological abnormalities in patients with thymoma.
J Clin Pathol, 56 (2003), pp. 12-16
PubMed PMID: 12499426. Pubmed Central PMCID: 1769851. Epub 2002/12/25. eng
C. Cunningham-Rundles, F.P. Siegal, S. Cunningham-Rundles, P. Lieberman.
Incidence of cancer in 98 patients with common varied immunodeficiency.
J Clin Immunol, 7 (1987), pp. 294-299
PubMed PMID: 3611296
R.A. Hermaszewski, A.D. Webster.
Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications.
Quart J Med, 86 (1993), pp. 31-42
PubMed PMID: 8438047
C. Cunningham-Rundles.
Hematologic complications of primary immune deficiencies.
Blood Rev, 16 (2002), pp. 61-64
PubMed PMID: 11913998
S.R. Gottesman, D. Haas, M. Ladanyi, E.L. Amorosi.
Peripheral T cell lymphoma in a patient with common variable immunodeficiency disease: case report and literature review.
Leukemia Lymphoma, 32 (1999), pp. 589-595
PubMed PMID: 10048433
A. Aghamohammadi, N. Parvaneh, F. Tirgari, F. Mahjoob, M. Movahedi, M. Gharagozlou, et al.
Lymphoma of mucosa-associated lymphoid tissue in common variable immunodeficiency.
Leukemia Lymphoma, 47 (2006 Feb), pp. 343-346
PubMed PMID: 16321869. Epub 2005/12/03. eng
F. Reichenberger, C. Wyser, M. Gonon, G. Cathomas, M. Tamm.
Pulmonary mucosa-associated lymphoid tissue lymphoma in a patient with common variable immunodeficiency syndrome.
Respiration Int Rev Thoracic Dis, 68 (2001), pp. 109-112
PubMed PMID: 11223743
H. Tcheurekdjian, O. Jenkins, R. Hostoffer.
Simultaneous nonparotid cranial mucosa-associated lymphoid tissue lymphoma and common variable immunodeficiency.
Ear Nose Throat J, 83 (2004), pp. 352-354
PubMed PMID: 15195883
M. Di Renzo, A.L. Pasqui, A. Auteri.
Common variable immunodeficiency: a review.
Clin Exp Med, 3 (2004), pp. 211-217
PubMed PMID: 15103511
G. Azizi, N. Rezaei, F. Kiaee, N. Tavakolinia, R. Yazdani, A. Mirshafiey, et al.
T-cell abnormalities in common variable immunodeficiency.
J Investig Allergol Clin Immunol, 26 (2016), pp. 233-243
PubMed PMID: 27374799. Epub 2016/07/05. eng
M. Malphettes, L. Gerard, M. Carmagnat, G. Mouillot, N. Vince, D. Boutboul, et al.
Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect.
Clin Infect Dis: Off Publ Infect Dis Soc Am, 49 (2009), pp. 1329-1338
PubMed PMID: 19807277
Y. Gao, S. Workman, S. Gadola, T. Elliott, B. Grimbacher, A.P. Williams.
Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells.
J Allergy Clin Immunol, 133 (2014), pp. 1420-1428
8 e1. PubMed PMID: 24582167
R.R. Barbosa, S.P. Silva, S.L. Silva, A.C. Melo, E. Pedro, M.P. Barbosa, et al.
Primary B-cell deficiencies reveal a link between human IL-17-producing CD4 T-cell homeostasis and B-cell differentiation.
PubMed PMID: 21826211. Pubmed Central PMCID: 3149619
R.X. Leng, H.F. Pan, D.Q. Ye, Y. Xu.
Potential roles of IL-9 in the pathogenesis of systemic lupus erythematosus.
Am J Clin Exp Immunol, 1 (2012), pp. 28-32
PubMed PMID: 23885312. Pubmed Central PMCID: 3714186
I. Glimelius, A. Edstrom, R.M. Amini, M. Fischer, G. Nilsson, C. Sundstrom, et al.
IL-9 expression contributes to the cellular composition in Hodgkin lymphoma.
Eur J Haematol, 76 (2006), pp. 278-283
PubMed PMID: 16519698
X. Lv, X. Wang.
The role of interleukin-9 in lymphoma.
Leukemia Lymphoma, 54 (2013), pp. 1367-1372
PubMed PMID: 23127115
L. Knoops, J.C. Renauld.
IL-9 and its receptor: from signal transduction to tumorigenesis.
Growth Factors, 22 (2004), pp. 207-215
PubMed PMID: 15621723
S.P. da Silva, E. Resnick, M. Lucas, J. Lortan, S. Patel, C. Cunningham-Rundles, et al.
Lymphoid proliferations of indeterminate malignant potential arising in adults with common variable immunodeficiency disorders: unusual case studies and immunohistological review in the light of possible causative events.
J Clin Immunol, 31 (2011), pp. 784-791
PubMed PMID: 21744182. Pubmed Central PMCID: 3428024
C. Ariatti, D. Rossi, D. Vivenza, E. Berra, G. Benevolo, M. Fontana, et al.
Molecular characterization of common variable immunodeficiency-related lymphomas.
Annali Italiani di Med Int: Org Uffic della Soc Ital Med Int, 16 (2001), pp. 163-169
PubMed PMID: 11692905
O. Ayyildiz, A. Altintas, A. Isikdogan, A. Tuzcu.
Aggressive natural killer cell leukemia in a patient with common variable immunodeficiency syndrome.
Gynec Endocrinol: Off J Int Soc Gynecol Endocrinol, 22 (2006), pp. 286-287
PubMed PMID: 16785152
J. Toh, R. Eisenberg, K. Bakirhan, A. Verma, A. Rubinstein.
Myelodysplastic syndrome and acute lymphocytic leukemia in common variable immunodeficiency (CVID).
J Clin Immunol, 36 (2016), pp. 366-369
PubMed PMID: 26993985
F.A. Hampson, A. Chandra, N.J. Screaton, A. Condliffe, D.S. Kumararatne, A.R. Exley, et al.
Respiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders.
Clin Radiol, 67 (2012), pp. 587-595
PubMed PMID: 22226567. Epub 2012/01/10. eng
M.A. Park, J.T. Li, J.B. Hagan, D.E. Maddox, R.S. Abraham.
Common variable immunodeficiency: a new look at an old disease.
PubMed PMID: 18692715. Epub 2008/08/12. eng
H. Abolhassani, B.T. Sagvand, T. Shokuhfar, B. Mirminachi, N. Rezaei, A. Aghamohammadi.
A review on guidelines for management and treatment of common variable immunodeficiency.
Exp Rev Clin Immunol, 9 (2013), pp. 561-574
quiz 75. PubMed PMID: 23730886. Epub 2013/06/05. eng
G. Azizi, V. Ziaee, M. Tavakol, T. Alinia, R. Yazdai, H. Mohammadi, et al.
Approach to the management of autoimmunity in primary immunodeficiency.
Scand J Immunol, (2016),
PubMed PMID: 27862144
C. Wehr, A.R. Gennery, C. Lindemans, A. Schulz, M. Hoenig, R. Marks, et al.
Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency.
J Allergy Clin Immunol, 135 (2015),
988-97 e6. PubMed PMID: 25595268. Epub 2015/01/18. eng
M.L. Ochtrop, S. Goldacker, A.M. May, M. Rizzi, R. Draeger, D. Hauschke, et al.
T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency.
PubMed PMID: 21576700. Epub 2011/05/18. eng
N. Rezaei, H. Abolhassani, A. Aghamohammadi, H.D. Ochs.
Indications and safety of intravenous and subcutaneous immunoglobulin therapy.
Exp Rev Clin Immunol, 7 (2011), pp. 301-316
PubMed PMID: 21595597. Epub 2011/05/21. eng
H. Abolhassani, M.H. Asgardoon, N. Rezaei, L. Hammarstrom, A. Aghamohammadi.
Different brands of intravenous immunoglobulin for primary immunodeficiencies: how to choose the best option for the patient?.
Exp Rev Clin Immunol, 11 (2015), pp. 1229-1243
PubMed PMID: 26289377. Epub 2015/08/21. eng
C.M. Kokron, P.R. Errante, M.T. Barros, G.V. Baracho, M.M. Camargo, J. Kalil, et al.
Clinical and laboratory aspects of common variable immunodeficiency.
An Acad Bras Cienc, 76 (2004), pp. 707-726
PubMed PMID: 15558152. Epub 2004/11/24. eng
E. Oksenhendler, L. Gerard, C. Fieschi, M. Malphettes, G. Mouillot, R. Jaussaud, et al.
Infections in 252 patients with common variable immunodeficiency.
Clin Infect Dis: Off Publ Infect Dis Soc Am, 46 (2008), pp. 1547-1554
PubMed PMID: 18419489. Epub 2008/04/19. eng
I. Quinti, C. Di Pietro, H. Martini, A.M. Pesce, F. Lombardi, M. Baumghartner, et al.
Health related quality of life in common variable immunodeficiency.
Yonsei Med J, 53 (2012), pp. 603-610
PubMed PMID: 22477006. Pubmed Central PMCID: 3343431. Epub 2012/04/06. eng
C. Rivoisy, L. Gerard, D. Boutboul, M. Malphettes, C. Fieschi, I. Durieu, et al.
Parental consanguinity is associated with a severe phenotype in common variable immunodeficiency.
J Clin Immunol, 32 (2012), pp. 98-105
PubMed PMID: 22002594. Epub 2011/10/18. eng
B.K.C. Sini, D. Levy, J. Pereira, A.B. Oliveira, A. Cohon, J. Kalil, S. Bydlowski, M.T. Barros.
Frequency of lymphomas in a cohort of common variable immunodeficiency (CVID) patients.
15th International Congress of Immunology (ICI),
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