Nonimmune binding of human immunoglobulins G and A by <i>Streptococcus pyogenes</i>: the role of this phenomenon in pathology

Abstract

M and M-like proteins are key pathogenicity factors of Streptococcus pyogenes, a widely prevalent and potentially lethal bacterium. These proteins confer resistance to the hosts innate and adaptive immune response by attracting specific human proteins to the streptococcal surface. The nonimmune binding of host immunoglobulins G (IgG) and A (IgA) to M and M-like proteins via their Fc domains was first described over 50 years ago, but its role in the pathogenicity of S. pyogenes remains unclear. This discovery has had a significant impact on the development of innovative diagnostic approaches, technologies, and tools in microbiology, immunology, and molecular biology. The nonimmune binding of immunoglobulins has been suggested to play a role in immune conditions on mucosal surfaces and their secretions, but not in blood plasma, while other studies suggest it protects microbes from phagocytosis in the hosts nonimmune blood. The Fc-binding effect has been shown to increase the pathogenicity of streptococci, contributing to the development of autoimmune diseases and tissue damage in experimental animals. The experimental autoimmune process can be prevented by administering purified Fc fragments of immunoglobulins to animals. Streptococcal diseases play a significant role in the pathogenesis of IgA-nephropathy (IgAN), a mesangial proliferative process caused by initial IgA-Fc deposition in renal mesangium cells. Literature suggests a relevance of recent ideas about the important role of nonimmune Ig binding in streptococcal diseases, and further efforts are required to study the binding of Fc fragments of IgG and IgA to M and M-like proteins of S. pyogenes, with the aim of developing preventive and potentially therapeutic applications. The paper speculates on the role of nonimmune Ig binding in streptococcal diseases, including cases with various mechanisms of development. These studies also focuses on preventive and potentially therapeutic applications of Fc fragments of IgG to M or M-like proteins of S. pyogenes.