Occurrence of autoantibodies for gastrointestinal autoimmune diseases in children with common variable immune deficiency and selected IgA deficiency

Abstract

IntroductionSelected IgA deficiency (IgAD) and common variable immune deficiency (CVID) are humoral immunity deficiencies frequent in children. In both these types of immunodeficiency, autoimmune diseases are present in 20–30% of patients, but the disease profiles are different between adults and children. Autoimmune diseases of the gastrointestinal tract (IBD) and celiac disease are typical for children with IgAD and CVID. Diagnosis is based on clinical symptoms, histology of jejunum and antibodies often preceding the onset of disease. However, the diagnosis of IBD and celiac disease is difficult in immune deficiency patients due to weaker or absent production of antibodies, and different jejunum histology, particular in CVID patients.AimDetection of antibodies for autoimmune diseases in children with diagnosis of CVID and IgAD.Material and methodsThe study included 43 children with CVID and 63 children with IgAD diagnosis. Antibodies typical for celiac disease (for endomysium, tissue transglutaminase and gliadin) were tested in IgA class (CVID patients), IgG class (IgAD, CVID patients) and found in 16 patients (3 – CVID, 13 – IgAD).ResultsAntibodies for IBD (for Saccharomyces cerevisiae antigen – ASCA, goblet cells – Gab, neutrophil’s cytoplasm – ANCA, pancreatic cells – Pab) were noted in 17 patients (7 – CVID, 10 – IgAD). Celiac disease was diagnosed in two children with mild and unspecific clinical symptoms followed by introduction of a gluten-free diet. The remaining children with present antibodies but without clinical symptoms involving the gastrointestinal tract are under careful clinical observation with antibody assay every 6 months.ConclusionsThe antibodies are produced despite impaired humoral immunity but the level might be low so the lower limit of positive results is postulated.

Rheumatologic complications in a cohort of 227 patients with common variable immunodeficiency

“…In our study, there was an association between a defect in specific antibody responses and negative results in related serologic test in patients with rheumatologic complications. Pituch‐Noworolska et al in 2013 evaluated autoantibodies in children with CVID and report that antibodies are produced despite impaired humoral immunity, but their level might be lower than immunocompetent individuals affected by autoimmunity. In another study, Milota et al described 2 patients with a combination of T1D and CVID with serious impairment of antibody production.…”

Approach to the Management of Autoimmunity in Primary Immunodeficiency

“…Moreover, in IgAD patients with coeliac disease, the production of anti‐EMA, AGA and AtTGA are preserved, but only in the IgG class. However, in some IgAD patients, despite the lack of IgA in serum, the presence and high levels of AtTGA have been reported in the IgA class .…”

“…An association between certain antibodies and the pathogenesis of autoimmune GI diseases has been established. For many years, the serologic diagnosis of coeliac disease was based on the detection of IgA anti‐endomysial antibodies (EMA), IgA and IgG antigliadin antibodies (AGA), and antitissue transglutaminase antibodies (AtTGA) as well as IgA antireticulin antibodies . It has been demonstrated that the levels of these autoantibodies in the serum of PID patients are often lower than in patients without PID .…”

Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?

“…It is well known that these diseases may share a common dysregulation of the ICOS molecule [ 65 ], and coexistence in the same family of patients with CD and CVID has been described [ 66 ]. Although celiac-like lesions can be observed in 30% of CVID patients, the true prevalence of CD in CVID is much lower, as reported in Table 3 [ 41 , 63 , 67 , 68 , 69 , 70 ], being 9.2% overall. Biagi et al [ 70 ] have observed that the histologic response to a GFD is the only reliable tool to establish the diagnosis of CD in CVID.…”

“…The prevalence of CD in sIgAD is much more than in the general population, ranging from 6.7%–20.6% as summarized in Table 2 [ 38 , 39 , 40 , 41 , 42 , 43 ]. On the other hand, sIgAD is more common in celiac patients, with a prevalence of 1:39 [ 44 ].…”