Antibodies against Four Proteins from a Streptococcus pyogenes Serotype M1 Strain and Levels of Circulating Mannan-Binding Lectin in Acute Poststreptococcal Glomerulonephritis

Abstract

Background: Responses against antigens from the potentially nephritogenic Streptococcus pyogenes serotype M1 in patients with acute poststreptococcal glomerulonephritis (AGN) were studied to seek indications of expression of these antigens during the preceding infection. Also, the question was asked whether the complement protein mannan-binding lectin (MBL) is required for development of the hypocomplementemia associated with AGN. Hypothetically, the lectin pathway might trigger the alternative pathway, which is consistently activated in AGN. Methods: Antibodies against three proteins associated with M1, M1 protein, streptococcal inhibitor of complement (SIC) and protein H, an IgG-binding protein, were determined by ELISA in 56 children and 17 adults with AGN. Antibodies against streptococcal cysteine proteinase, which is produced by all serotypes of S. pyogenes, were also examined. MBL concentrations were measured in the same 71 patients by a sandwich ELISA. Results: Increased concentrations of antibodies were found against all four streptococcal proteins, albeit not uniformly distributed between different subgroups of patients. The prevalence of low MBL concentrations (<100 µg/l) including 2 patients with undetectable MBL (<10 µg/l) was similar in AGN (11%) and in controls (16%). Conclusions: Our results give evidence of exposure to SIC and protein H in conjunction with AGN. This implies that SIC and protein H and/or cross-reacting proteins may have a role in the pathogenesis of AGN or that streptococci expressing SIC or protein H are nephritogenic for other reasons. The finding of MBL-deficient individuals among the patients demonstrates that MBL is not necessary for the recruitment of complement in AGN.