The alternative pathway of the complement system is involved in renal damage of human pauci-immune AAV.

SummaryBackground and objectives The cross-reactive antigen(s) of tubulointerstitial nephritis and uveitis (TINU) syndrome from renal tubulointerstitia and ocular tissue remain unidentified. The authors' recent study demonstrated that the presence of serum IgG autoantibodies against modified C-reactive protein (mCRP) was closely associated with the intensity of tubulointerstitial lesions in lupus nephritis. The study presented here investigates the possible role of IgG autoantibodies against mCRP in patients with TINU syndrome.Design, setting, participants, & measurements mCRP autoantibodies were screened by ELISA with purified human C-reactive protein in 9 patients with TINU syndrome, 11 with drug-associated acute interstitial nephritis, 20 with IgA nephropathy, 19 with minimal change disease, 20 with ANCA-associated vasculitis, 6 with Sjogren's syndrome, and 12 with amyloidosis. mCRP expression was analyzed by immunohistochemistry in renal biopsy specimens from the 9 patients with TINU syndrome and 40 from disease controls. Frozen normal human kidney and iris were used to demonstrate co-localization of human IgG and mCRP from patients with TINU syndrome with laser scanning confocal microscopy. ResultsThe mCRP autoantibodies were detected in all nine patients with TINU syndrome, significantly higher than that of those with disease controls (P Ͻ 0.05). The renal histologic score of mCRP in TINU syndrome was significantly higher than that in disease controls (P Ͻ 0.05). The staining of mCRP and human IgG were co-localized in renal and ocular tissues. ConclusionsIt is concluded that mCRP might be a target autoantigen in TINU syndrome.

Complement deposition was not rare in renal histopathology of human ANCA-associated pauci-immune glomerulonephritis, which was associated with more severe renal injury.

Complement activation was involved in renal damage of human ANCA-negative pauci-immune CrGN but with heterogeneous activation pathways. Positive staining of C4d and MBL might be associated with poor renal outcome.