Abnormalities of the IgA immune system in members of unrelated pedigrees from patients with IgA nephropathy

Abstract

SUMMARY In the last few years many investigators have reported the recurrence of primary IgA nephropathy (IgAN) or the presence of persistent microhaematuria and/or proteinuria in family members of patients with IgAN. Our study was undertaken to investigate the relevance of abnormalities in the regulation of the IgA and IgM immune system in microhacmaturic and asymptomatic family members of IgAN patients. Fifty-four out of 120 members of nine unrelated pedigrees were examined by urinalysis; polymeric IgA (pIgA). IgA rheumatoid factor (IgARF), IgAI-IgG immune complexes (IgAl-IgG IC) and IgAl-IgM IC, and other immunoglobulins were measured in serum samples. Moreover, we studied the production of immunoglobulins. pIgA and IgARF by peripheral blood mononuclear cells (PBMC) in basal conditions and after pokeweed mitogen (PWM) stimulation. Our data demonstrate that persistent mierohaematuria was present in 24% of relatives. High serum levels of IgA. mainly pIgA and IgARF, IgAI-IgG IC and IgAl-IgM IC occurred in 66% of relatives. Abnormal spontaneous production of IgA by PBMC and after PWM stimulation was present in 64% of family members. Interestingly, high scrum levels of IgM and abnormal production of this immunoglobulin by PBMC were observed in relatives. However, the immunological abnormalities did not correlate in any way with the presence of urinary abnormalities such as microhaematuria. which was most likely determined by an underlying glomerular alteration.