Pathogenesis and therapy of IgA nephropathy

Abstract

IgA nephropathy (IgAN) is the most common chronic glomerulonephritis of unknown cause. Two factors are important in the pathogenesis of IgAN; one is IgA immune complex (IgA-IC) formation and the other is IgA-IC deposition to mesangium. For the formation of IgA-IC, antibody of IgA class, T-cells which help the generation of IgA antibody, and antigen are necessary. The serum IgA level in patients with IgAN is elevated probably due not only to the activation of B-cell but also to the hyperactivity of alpha beta chain positive T-cells. Analysis of the immunoglobulin gene of IgAN patients indicated that the genetic polymorphism could be correlated with the production of IgA antibody. The gamma delta chain positive T-cell may play some role for the formation of IgA-IC. Food, bacteria, viral proteins are reported to be the antigens of IgA-IC. Regarding to IgA-IC deposition, cytokines from T-cells and the molecular weight of IgA-IC are also indispensable factors. Clinically, long-term prognosis of IgAN are not unanimously the same. Approximately 15% patients progress to renal failure over a period of 10 years, and 25% to renal failure within 20 years. Roughly, patients can be classified into three groups in view of clinical course. First group maintains stable renal function for more than 20 years, second exhibits progressive course in more than 20 years and third progresses more rapidly than the second. Although the exact mechanism(s) governing the fate of renal function in IgAN is unclear, non-immunological factors, such as intraglomerular hypertension, are presumed to participate in its progression.(ABSTRACT TRUNCATED AT 250 WORDS)