Streptococcal M protein enhances TGF‐β production and increases surface IgA‐positive B cells in vitro in IgA nephropathy

Abstract

High serum levels and enhanced in vitro production of IgA are observed in more than half of patients with IgA nephropathy (IgAN); and transforming forming growth factor-beta (TGF-beta) is certain IgA class switching factor. On the other hand, macroscopic haematuria appears frequently with upper respiratory infection as tonsillitis in IgAN.We compared the lymphocytic response to in-vitro stimulation by group A streptococcal M proteins of apparent virulence factor between IgAN, non-proliferative glomerulonephritis (NPGN), and normal subjects. M proteins were extracted from group A streptococcal strain type 5 and type 12 determined serologically.M protein-induced proliferation of lymphocytes from IgAN was higher than in NPGN but not in healthy control subjects. Flow cytometric analysis indicated that stimulation by M protein extracts derived from type 5 streptococci (M5) increased surface IgA-positive B cells in IgAN, but did not activate the production of soluble IgA. We also showed that M5 induced significant increases in TGF-beta, in culture supernatants of lymphocytes from patients with IgAN.Our results suggest that Streptococcal infection may play an important role in the pathogenesis of IgAN by stimulating IgA production through TGF-beta synthesis.