Serum levels and in vitro production of IgA subclasses in patients with primary IgA nephropathy
van den Wall Bake, A.W.; Daha, M.R.; van der Ark, A.; Hiemstra, P.S.; Radl, J.; van Es, L.A.
Clinical and Experimental Immunology 74(1): 115-120
1988
ISSN/ISBN: 0009-9104 PMID: 3219797 Document Number: 317518
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 < 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 < 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 < 0.05) and in PWM stimualted cultures (P < 0.05) and in PWM stimualted cultures (P < 0.01). Polymeric IgA and polymeric IgA1 production were not higher in patients than in controls. IgM production in unstimulated cultures was significantly (P < 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.