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

Abstract

Background. 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-β (TGF-β) is certain IgA class switching factor. On the other hand, macroscopic haematuria appears frequently with upper respiratory infection as tonsillitis in IgAN. Methods. 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. Results. 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-β, in culture supernatants of lymphocytes from patients with IgAN. Conclusion. Our results suggest that Streptococcal infection may play an important role in the pathogenesis of IgAN by stimulating IgA production through TGF-β synthesis.