Background and objectives: IgA nephropathy is the most common primary glomerulonephritis worldwide. Previous research demonstrated that collectin11, an initiator of complement lectin pathway, was involved in both acute kidney injury and chronic tubulointerstitial fibrosis. Here, we investigated the potential role of collectin11 in the pathogenesis of IgA nephropathy.
Design, setting, participants, and measurements: The deposition of collectin11 and other complement proteins was detected in glomeruli of 60 participants with IgA nephropathy by immunofluorescence. In vitro, human mesangial cells were treated with IgA1-containing immune complexes derived from participants with IgA nephropathy. Then, the expression of collectin11 in mesangial cells was examined by RT-qPCR and immunofluorescence. The codeposition of collctin11 with IgA1 or C3 on mesangial cells was detected by immunofluorescence and proximity ligation assays.
Results: 37% participants with IgA nephropathy (22/60) showed codeposition of collectin11 with IgA in the glomerular mesangium. Using an injury model of mesangial cells, we demonstrated that IgA1-immune complexes derived from participants with IgA nephropathy increased the secretion of collectin11 in mesangial cells with the subsequent deposition of collectin11 on the cell surface via the interaction with deposited IgA1-immune complexes. In vitro, we found that collectin11 bound to IgA1-immune complexes in a dose-dependent but calcium-independent manner. Furthermore, deposited collectin11 initiated the activation of complement and accelerated the deposition of C3 on mesangial cells.
Conclusions: In situ-produced collectin11 by mesangial cells might play an essential role in kidney injury in a subset of patients with IgA nephropathy through the induction of complement activation.
How Immune Complexes from Certain IgG NAbs and Any F(ab′)2 Can Mediate Excessive Complement Activation
