In vitro immunoglobulin production in relatives of patients with IgA nephropathy

We hypothesized that the altered immunoglobulin synthesis and/or lymphocyte function apparent in patients with IgA nephropathy might be, at least partially, genetically determined. To address this hypothesis, immunoglobulin production by peripheral blood mononuclear cells in 22 patients with IgA nephropathy and 44 of their first degree relatives was investigated. Spontaneous overproduction of IgA1 and IgM from patients' PBMC was found. After pokeweed mitogen stimulation, both patients and relatives produced significantly more IgA1 and IgM than normal subjects. However, relatives showed a higher index of stimulation by pokeweed mitogen compared to both normals and patients. No differences were revealed in IgA2 or IgG subclass production among the groups. We propose that patients with IgAN have defects in immunoregulation that likely depend upon the genetic substrate in the patients' relatives. Such defect may reside not with the balance between help for and suppression of a particular isotype, but rather with the overall balance of isotypes in response to a particular antigenic challenge.