Modified C-reactive protein might be a target autoantigen of TINU syndrome

Abstract

Background 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.

Results: The mCRP autoantibodies were detected in all nine patients with TINU syndrome, significantly higher than that of those with disease controls (P < 0.05). The renal histologic score of mCRP in TINU syndrome was significantly higher than that in disease controls (P < 0.05). The staining of mCRP and human IgG were co-localized in renal and ocular tissues.

Conclusions: It is concluded that mCRP might be a target autoantigen in TINU syndrome.

Figure 1.

Levels of serum mCRP autoantibodies from patients with TINU syndrome and controls. The horizontal dashed line indicates the cutoff value (17%).

Figure 2.

The change of serum mCRP autoantibody levels in patients with TINU syndrome from active phase to remission and the levels of serum mCRP autoantibodies from one patient (patient 8) with sequential sera. The horizontal dashed line indicates the cutoff value (17%).

Figure 3.

Staining of mCRP by immunohistochemistry in patients with TINU syndrome with monoclonal antibodies against human mCRP. The mCRP signal (brown) was demonstrated using the HRP technique in renal biopsy tissues. Nuclei were counterstained with hematoxylin. (A) Renal histologic score of 3+ for mCRP, with the cytoplasm of renal tubular epithelial cells and interstitia showing mCRP positivity (arrows), 200×. (B) Negative control of the same renal tissue, 200×.

Figure 4.

Co-localization of mCRP and IgG from patients with TINU syndrome by immunofluorescence using laser scanning confocal microscopy. (A) Indirect immunofluorescence with anti-human IgG antibodies indicated focal cytoplasmic staining in renal tubular cells in a renal biopsy section (600×). (B) Direct immunofluorescence with anti-mCRP antibodies indicated focal cytoplasmic staining in tubular cells of the same renal biopsy section. (C) The merged image of expression of mCRP and human IgG from a patient with TINU syndrome (600×). (D) Indirect immunofluorescence with anti-IgG antibodies indicated membranous positive staining in human ciliary body cells and iris (600×). (E) Direct immunofluorescence with anti-mCRP antibodies indicated staining in ciliary body cells and iris of the same ocular section. (F) The merged image of expression of mCRP and human IgG from a patient with TINU syndrome (600×).