Serum levels and in vitro production of IgA subclasses in patients with primary IgA nephropathy.

Patients with primary IgA nephropathy have deposits of IgA1 in their kidneys, and increased plasma levels of macromolecular IgA1. Total serum IgA concentrations are frequently elevated, but studies on the subclass distribution have been few and conflicting. Several investigators found that production of IgA by peripheral blood lymphocytes in culture is increased. However, the distribution of the IgA subclasses produced has not been studied previously. We studied the serum IgA subclasses in 14 patients with IgA nephropathy, and found a significant (P less than 0.001) increase in IgA1 (3.71 +/- 1.34 mg/ml, mean +/- s.d.) compared with controls (1.77 +/- 1.10 mg/ml). Serum IgA2 was not different in patients and controls. The ratio of serum IgA1 to total IgA was also significantly (P less than 0.001) higher in patients (92.2 +/- 4.9%) than in controls (80.2 +/- 6.6%). Studies of immunoglobulin production by peripheral blood mononuclear cells showed a significant increase in IgA1 synthesis, expressed as a fraction of total IgA synthesis in unstimulated cultures (P less than 0.05) and in PWM stimulated cultures (P less than 0.01). Polymeric IgA and polymeric IgA1 production were not higher in patients than in controls. IgM production in unstimulated cultures was significantly (P less than 0.05) higher in patients than in controls. Together with the observed deposition of exclusively IgA1 in the mesangium, our results indicate that patients with IgA nephropathy preferentially produce antibodies of the IgA1 subclass.