Activation of complement in IgA nephropathy

Considerable evidence supports a role for the complement system in the pathogenesis of IgA nephropathy (IgAN). The alternative pathway components C3 and properdin (P) and the membrane attack complex (C5b-9) are generally found in the mesangial deposits in IgAN, while the classical pathway components C1q and C4 are usually absent. This pattern of immunofluorescence staining for complement components suggests activation of the alternative and terminal pathways in most patients. Despite normal serum concentrations of C3 and other complement proteins, fragments generated by activation of C3, including iC3b, C3d, and iC3b-C3d neoantigen, and sometimes C4, are often detected in plasma. We found that the severity of the histologic changes in the renal biopsy specimens correlated with plasma iC3b-C3d neoantigen concentrations as measured by an enzyme-linked immunosorbent assay. However, no other clinical feature correlated with the plasma concentrations of this neoantigen.