Familial aggregation of IgAD and autoimmunity
Introduction
Selective IgA deficiency (IgAD) is defined as serum IgA levels equal or less than 0.07 g/L, with normal levels of serum IgG and IgM [1]. Selective IgA deficiency has a prevalence of approximately 1/600 in North-European populations, making it one of the most common primary immunodeficiencies, only mannan-binding lectin deficiency being more common [2], [3]. The prevalence of IgAD in Icelandic blood donors has been estimated to be 1:572 (1999–2001; Jörgensen GH; unpublished data) and 1:633 [4].
Clinical manifestations associated with IgAD are dependent upon the cohort studied. Thus, most studies published so far are based upon relatively healthy cohorts of blood donors, whereas, studies of hospital cohorts of IgAD individuals, have been associated with infections, allergies and autoimmune diseases [5], [6], [7], [8].
The prevalence of autoimmunity has been estimated to be around 3–5% in western countries [9], [10], [11]. However, the prevalence of autoimmunity in IgAD individuals has been shown to be highly variable, ranging from 7 to 36% in symptomatic IgAD individuals [5], [12]. A strong association has been found with systemic autoimmune diseases and the prevalence of IgAD among SLE patients has been found to be 0.94–5.2% [13], [14], [15] and 0.25–1.6% among RA patients [7], [13]. Furthermore, organ specific autoimmune diseases such as DM type I [16], [17], autoimmune thyroiditis [18], [19], coeliac disease [20], myasthenia gravis [21], psoriasis [22], [23], idiopathic thrombocytopenia (ITP) [24] and pemphigus [25] might also be associated with IgAD. However, the possible familial aggregation of IgAD and autoimmunity has not been thoroughly investigated.
Several studies have indicated an increased prevalence of autoantibodies in IgAD individuals, regardless whether or not they have been diagnosed with autoimmunity. IgAD individuals without an autoimmune disease have autoantibodies that are most often associated with systemic autoimmune diseases, such as rheumatoid factor (13–30%), anti-nuclear antibodies (2.7–13%) and anti-cardiolipin (37–53%) [26], [27], [28]. Autoantibodies linked to organ-specific autoimmune diseases are less common although anti-thyroglobulin and anti-thyroid microsomeal antibodies have been observed in 10–15% of IgAD individuals [26], [29]. Furthermore, IgA deficiency has also been found to be more common among individuals positive for these autoantibodies [7], [26], [27], [30].
In the present study, we evaluated the prevalence of autoimmunity in both IgAD individuals and their 1° family members. Our findings suggest an overall autoimmunity prevalence of 25% in adult IgAD individuals and 10% among the 1° relatives. These findings indicate that IgAD may be associated with genetic factors that predisposes to autoimmunity.
Section snippets
Demography of the IgAD cohort
A total of 43 IgAD individuals (32 adults and 11 children) were identified by three different routes. First, by screening for IgAD in 4004 blood donors at the Icelandic blood bank. In total, 7 blood donors were IgAD, and 5 participated in this study. Second, by re-evaluating IgAD individuals from a previous IgAD study (1974–1979) in Iceland [4]. Originally 24 IgAD individuals were found by screening of more than 15.000 blood donors. Of those, still alive and willing to participate, a total of
Autoimmunity among IgAD individuals
The prevalence of autoimmunity among the IgAD cohort is shown in Table 1. Among the 32 adult IgAD individuals, 8 (25%) were found to have definite autoimmunity and four had two autoimmune diseases. None of the 11 children with IgAD had autoimmunity. Two of 16 blood donors had autoimmunity (12.5%) and both were from the older IgAD blood bank screening cohort from 1974 to 1979 who had subsequently developed their disease.
As demonstrated in Fig. 1, the organ specific diseases were diagnosed at an
Discussion
In this study we observed a remarkably high prevalence of autoimmunity in both the adult IgAD cohort (25%) and their 1° relative cohort (10%). In comparison, autoimmunity has been estimated to be around 5% within the general population [9], [10], [11].
Interestingly, we did not find a major difference in the occurrence of organ specific versus systemic autoimmune diseases in either group. However, organ specific autoimmunity was more likely to be diagnosed at a younger age (before 40 years of
Conflict of interest declaration
The study is financially supported by the Landspitali University Hospital Research Fund and the Icelandic Research Fund.
There are no conflicts of interest to declare, by any of the authors.
Capsule summary
Autoimmune diseases are common in adult patients with selective IgA deficiency (25%) and their 1° relatives (10%). A total of 42% of IgAD individuals have 1° relatives with autoimmunity. These findings demonstrate a strong predisposition of autoimmunity within families with IgA deficiency.
Acknowledgments
The authors would like to thank Professor Helgi Valdimarsson for the assistance in the preparation of this manuscript.
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