INDUCTION OF UNRESPONSIVENESS AGAINST IGA IN IGA-DEFICIENT PATIENTS ON SUBCUTANEOUS IMMUNOGLOBULIN INFUSION THERAPY

Patients with IgA deficiency often demonstrate circulating antibodies against IgA, which have been suggested to be associated with transfusi on reactions. Sera from three patients with common variable immunodefi ciency (CVID) and one with a selective IgA deficiency with anti-IgA an tibodies receiving subcutaneous gammaglobulin replacement therapy were analysed for serum levels of IgG, IgA and anti-IgA before and during a treatment period of 4-7 years. Treatment with gammaglobulin preparat ions containing significant amounts of IgA (< 5 mg/ml) resulted in a d ecrease or disappearance of the anti-IEA antibodies. Analysis of serum fractions, however, revealed anti-IgA activity in the complex-contain ing fractions. In vitro experiments gave similar results with a shift of anti-IgA activity from the monomeric to the complex-containing frac tions (that could not be detected in whole serum). When the patients w ere subsequently switched to treatment with a preparation containing l ess IgA (< 80 mu g/ml) or made an interruption in the treatment schedu le, the anti-IgA antibodies reappeared, importantly, however, one of t he patients lost his anti-IgA activity during a 3-month period on the preparation containing the higher IgA levels, and these antibodies did not reappear after switching to the low IgA-containing preparation. A fter 5 years on this preparation, anti-IgA can still not be detected, suggesting induction of unresponsiveness.