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Vol. 46. Issue 2.
Pages 127-135 (March - April 2018)
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Vol. 46. Issue 2.
Pages 127-135 (March - April 2018)
Original Article
DOI: 10.1016/j.aller.2017.04.004
Autoimmunity and its association with regulatory T cells and B cell subsets in patients with common variable immunodeficiency
G. Azizia,b,c,d, H. Abolhassanib,c,e, F. Kiaeeb,c, N. Tavakoliniab,c, H. Rafiemaneshf, R. Yazdanib,c, SA. Mahdavianig, S. Mohammadikhajehdehib,c, M. Tavakolh, V. Ziaeei, B. Negahdarij, J. Mohammadik, A. Mirshafieyl,
Corresponding author

Corresponding authors.
, A. Aghamohammadib,c,
Corresponding author

Corresponding authors.
a Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
b Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
c Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran
d Department of Laboratory Medicine, Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran
e Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
f Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
g Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
h Department of Allergy and Clinical Immunology, Shahid Bahonar Hospital, Alborz University of Medical Sciences, Karaj, Iran
i Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
j School of Advanced Technologies in Medicine, Department of Medical Biotechnology, Tehran University of Medical Sciences, Tehran, Iran
k Department of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
l Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Tables (3)
Table 1. Demographic and corresponding immunological data for CVID patients at the time of diagnosis.
Table 2. The frequency of various types of autoimmune diseases in CVID patients.
Table 3. Comparison of immune-related clinical manifestations between CVID patients with autoimmunity vs. CVID patients without autoimmunity.
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Common variable immunodeficiency (CVID) is one of the most prevalent symptomatic primary immunodeficiencies (PIDs), which manifests a wide clinical variability such as autoimmunity, as well as T cell and B cell abnormalities.


A total of 72 patients with CVID were enrolled in this study. Patients were evaluated for clinical manifestations and classified according to the presence or absence of autoimmune disease. We measured regulatory T cells (Tregs) and B-cell subsets using flow cytometry, as well as specific antibody response (SAR) to pneumococcal vaccine, autoantibodies and anti-IgA in patients.


Twenty-nine patients (40.3%) have shown at least one autoimmune manifestation. Autoimmune cytopenias and autoimmune gastrointestinal diseases were the most common. A significant association was detected between autoimmunity and presence of hepatomegaly and splenomegaly. Among CVID patients, 38.5% and 79.3% presented a defect in Tregs and switched memory B-cells, respectively, whereas 69.0% presented CD21low B cell expansion. Among patients with a defect in Treg, switched memory and CD21low B cell, the frequency of autoimmunity was 80.0%, 52.2% and 55.0%, respectively. A negative correlation was observed between the frequency of Tregs and CD21low B cell population. 82.2% of patients had a defective SAR which was associated with the lack of autoantibodies.


Autoimmunity may be the first clinical manifestation of CVID, thus routine screening of immunoglobulins is suggested for patients with autoimmunity. Lack of SAR in CVID is associated with the lack of specific autoantibodies in patients with autoimmunity. It is suggested that physicians use alternative diagnostic procedures.

Common variable immunodeficiency
Regulatory T cells
B cells


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