The influences of α-hemolytic Streptococcus on class switching and complement activation of human tonsillar cells in IgA nephropathy

Abstract

While β-hemolytic streptococcus (β-HS) infections are known to predispose patients to acute poststreptococcal glomerulonephritis, there is evidence that implicates α-hemolytic streptococcus (α-HS) in IgA nephropathy (IgAN). The alternative pathway of the complement system has also been implicated in IgAN. We aimed to explore the association between α-HS and complement activation in human tonsillar mononuclear cells (TMCs) in IgAN. In our study, α-HS induced higher IgA levels than IgG levels, while β-HS increased higher IgG levels than IgA levels with more activation-induced cytidine deaminase, in TMCs in the IgAN group. Aberrant IgA1 O-glycosylation levels were higher in IgAN patients with α-HS. C3 and C3b expression was decreased in IgAN patients, but in chronic tonsillitis control patients, the expression decreased only after stimulation with β-HS. Complement factor B and H (CFH) mRNA increased, but the CFH concentration in culture supernatants decreased with α-HS. The percentage of CD19 + CD35 + cells/complement receptor 1 (CR1) decreased with α-HS more than with β-HS, while CD19 + CD21 + cells/complement receptor 2 (CR2) increased more with β-HS than with α-HS. The component nephritis-associated plasmin receptor (NAPlr) of α-HS was not detected on tonsillar or kidney tissues in IgAN patients and was positive on cultured TMCs and mesangial cells. We concluded that α-HS induced the secretion of aberrantly O-glycosylated IgA while decreasing the levels of the inhibitory factor CFH in culture supernatants and CR1 + B cells. These findings provide testable mechanisms that relate α-HS infection to abnormal mucosal responses involving the alternative complement pathway in IgAN.

Keywords: Alternative complement pathway; Hemolytic streptococcus; IgA nephropathy; Tonsillar mononuclear cells.