IN-VITRO IMMUNOGLOBULIN PRODUCTION IN RELATIVES OF PATIENTS WITH IGA NEPHROPATHY

We hypothesized that the altered immunoglobulin synthesis and/or lymph ocyte function apparent in patients with IgA nephropathy might be, at least partially, genetically determined. To address this hypothesis, i mmunoglobulin production by peripheral blood mononuclear cells in 22 p atients with IgA nephropathy and 44 of their first degree relatives wa s investigated. Spontaneous overproduction of IgA1 and IgM from patien ts' PBMC was found. After pokeweed mitogen stimulation, both patients and relatives produced significantly more IgA1 and IgM than normal sub jects. However, relatives showed a higher index of stimulation by poke weed mitogen compared to both normals and patients. No differences wer e revealed in IgA2 or IgG subclass production among the groups. We pro pose that patients with IgAN have defects in immunoregulation that lik ely depend upon the genetic substrate in the patients' relatives. Such defect may reside not with the balance between help for and suppressi on of a particular isotype, but rather with the overall balance of iso types in response to a particular antigenic challenge.