Elevated IgG against the C region of streptococcal M protein and its immunodeterminants in patients with poststreptococcal acute glomerulonephritis

Objective: To determine the immune responses to the streptococcal M protein in patients with poststreptococcal acute glomerulonephritis (PSAGN). Study design: The gene coding type 12 M protein of group A streptococcus (M12), a known PSAGN-associated serotype, was cloned and expressed in Escherichia coli to investigate the specific immune responses to the M12 protein in patients with PSAGN. Recombinant M proteins for the variable N- terminal half (AB region) and conserved C-terminal half (G region) were produced separately. IgG titers against each region were measured by enzyme- linked immunosorbent assay in patients with PSAGN (n = 51), uncomplicated streptococcal pharyngitis (n = 26), chronic glomerulonephritis (n = 10), and in healthy control subjects (n = 51). Immunodominant domains within the M protein in PSAGN were further investigated by use of overlapping synthetic peptides. Results: IgG titers against the C region, but not the AB region, were markedly higher in the PSAGN group than in other groups (p < 0.01), and these titers were maintained for at least several months after antistreptolysin O or antistreptokinase levels had returned to normal. Studies with overlapping synthetic peptides demonstrated that increased IgG reactivity was observed against the C repeat blocks. Conclusion: IgG titers against the C region are significantly elevated in patients with PSAGN, and it may be a diagnostic marker for PSAGN.