Cross-reactive antibodies induced by xenogeneic IgA can cause selective IgA deficiency.

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Selective immunoglobulin A deficiency (sIgAD ) is the most common immunodeficiency in humans . Auto-reactive antibodies to human immunoglobulin A (IgA ) are found in the serum of 20 -40 % of individuals with sIgAD . It is unknown whether these antibodies play a role in the pathogenesis of this immunodeficiency and although the prevailing thought is that they are secondary to the onset of sIgAD , there is very little , if any , support for this notion . Here , we propose that anti-IgA antibodies are in fact responsible for the removal of IgA from serum , and that the inducing antigen is most probably a xenogeneic IgA . This hypothesis is based on data obtained from an sIgAD patient in whom changes in dietary consumption of beef and /or bovine dairy products resulted in changes in anti-IgA levels in the serum . To test the hypothesis , the presence of anti-bovine IgA antibodies was tested by a highly specific enzyme-linked immunosorbent assay in serum samples from IgA-deficient and control individuals . All 13 sIgAD individuals with anti-IgA antibodies had a higher titer against bovine IgA than against human IgA . Of 23 control individuals , a surprisingly high proportion (65 %) was also found to have IgG anti-bovine IgA antibodies . These results support the hypothesis that the anti-human IgA antibodies found in IgA-deficient individuals are originally produced against bovine IgA . These antibodies are found in many normal individuals , but only in cases where they cross react with endogenous human IgA , sIgAD may develop .