Anti-IgA Antibodies in Pregnancy

Abstract

A survey of 28,000 pregnant women revealed an incidence of IgA deficiency (serum IgA less than 1 mg per deciliter) of 1 in 450, which is identical to that in a normal blood-donor population of both sexes. Using an enzyme-linked immunosorbent assay (ELISA) in a study of 61 serum samples from IgA-deficient pregnant women, we observed antibodies to IgA2 alone in 20 per cent, as compared with 7.5 per cent of pregnant women not deficient in IgA and no IgA-deficient blood donors. Antibodies reacting with IgA1 alone were present in occasional serum samples (2 to 7 per cent) from all groups studied, and class-specific anti-IgA antibodies were present in 17 per cent of IgA-deficient blood donors and in 16 per cent of IgA-deficient pregnant women. Blocking experiments showed that some serum samples contained an antibody that reacted with both IgA1 and IgA2, whereas others contained two antibodies, one reacting with IgA1 and the other with IgA2. The anti-IgA2 antibodies tended to diminish in titer after delivery. The ELISA was, as expected, more sensitive than the hemagglutination assay. The offspring of IgA-deficient mothers (but not of IgA-deficient fathers) had levels of serum IgA below the normal mean (21 of 27); 12 had levels more than 1 S.D., and seven had levels more than 2 S.D., below the normal mean. Of the seven infants with serum IgA levels more than 2 S.D. below the normal age-related mean, five had mothers with anti-IgA antibodies during gestation. It is possible that maternal anti-IgA exerts a transplacental effect on the fetal immune system, causing IgA deficiency in some instances.

Immunoglobulin Replacement Therapy in Primary Antibody Deficiency Diseases – Maximizing Success

“…IgA deficiency is occasionally familial. A mother to child inheritance has been reported, secondary to the transplacental passage of maternal anti-IgA antibodies [12]. The link between IgA deficiency and CVID is not clear, but IgA deficiency and CVID can be observed either longitudinally in 1 patient or in 2 patients from the same family.…”

Selective IgA Deficiency and Autoimmunity

“…Accordingly, between 9 and 44% of subjects with selective IgA deficiency have detectable anti-IgA antibod ies [3,34,82]. Anti-IgA antibodies have been found more frequently in IgA-deficient patients with associated au toimmune diseases (81% of patients) than in IgA-deficient individuals without autoimmune diseases (22% of sub jects) [83], These antibodies are also more frequent in IgA-deficient subjects with an associated IgG2 deficiency [72].…”

“…Thus, instances of common variable immunodeficiency have been attributed to antibodies against B cells [56,119] and antibodies against IgA-producing B cells may contribute to some cases of selective IgA deficiency [31,32,34], In these sit uations, the immunodeficiency is secondary to the autoim munity, and is merely a symptom of it. However, only a small subset of selective IgA deficiency can be explained on this basis, since in most cases this defect is congenital and, as a result, precedes the autoimmune disease.…”

“…These autoantibodies may play an active role in the induction and/or persistence of selective IgA deficiency, and indeed anti-IgA antibodies can inhibit IgA synthesis in vitro [31,32], In this regard, the fact that IgA deficiency occurs more frequently in children from af fected mothers than in children from affected fathers [23] may be explained by transplacental passage of maternal anti-IgA antibodies which may interfere with the child's developing IgA system [33], Consistent with this hypothe sis, offspring of IgA-deficient mothers who have been ex posed to circulating anti-IgA antibodies during gestation tend to have lower serum IgA levels than offspring of IgAdeficient mothers without anti-IgA antibodies [34], Interestingly, selective IgA deficiency has been trans ferred to one child through bone marrow transplantation from an HLA-identical, IgA-deficient sibling [35], suggest ing that bone marrow hematopoietic precursors bear the information for this immunodeficiency.…”

Follow-Up of Anti-IgA Antibodies in Primary Immunodeficient Patients Treated with γ-Globulin

“…Patients on IMGG received doses ranging from 50 to 75 mg/kg every fortnight, and for IVGG 200-300 mg/kg Anti-IgA antibodies are found in small amounts in all normal individuals [1]. Elevated levels of these autoantibo dies have been reported in a few normal adults [2,3], pregnant women [4], patients suffering from systemic lupus erythematosus and rheumatoid arthritis [5], selected IgA deficiency [6] and other primary immunodeficient patients (ID) [7], as well as in multitransfused patients [2] and hypo gammaglobulinémies treated with 7-globulin [8][9][10][11][12]. In these cases, a relationship between exogenous IgA admin istration, anti-IgA antibodies and adverse reactions to the therapy has been suggested.…”