Abstract
A 44 year old woman with common variable immunodeficiency developed severe anaphylactic reactions to intravenous gammaglobulin. Analysis of her serum prior to the infusion of gammaglobulin was thus analyzed and the tests revealed a complete absence of free IgA, presence of an IgG autoantibody to IgA, IgA-IgG circulating immune complexes, and depressed levels of hemolytic C3 associated with elevated levels of C3a and C3d. The IgA-IgG complexes did not clear from the circulation even after six months following cessation of gammaglobulin infusions. Analysis of the complexes isolated by sucrose density gradient ultracentrifugation showed that they bind to solid phase F(ab')2 anti-C1q, have a high molecular weight (greater than 19s), activate the complement (C) system via the classical pathway in vitro and are comprised of IgG and IgA. These data suggest that in this patient an autoantibody response to IgA was probably associated with persistent endogenous production of IgA yielding IgG-IgA circulating immune complexes and activation of the complement system. Although the patient has no free IgA and no surface IgA bearing B cells, her peripheral blood lymphocytes were shown to contain cells capable of secreting IgA. Low levels of IgM and IgG were detectable in her serum, and B cells bearing surface IgM, IgG and IgD were present in normal numbers in the blood.
