Modified C-Reactive Protein Might be a Target Autoantigen of TINU Syndrome

Abstract

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.

Tubulointerstitial Nephritis with Uveitis in Chinese Adults

“…A limitation of this test is that mCRP-Ab can be detected in several other chronic diseases such as SLE (29,30) and chronic hepatitis C infection (31). We also identified some discrepancy between the normative value of mCRP-Ab in this study compared with our previous report (21). We speculate that this discrepancy was likely due to the instability of mCRP-Ab in the serum sample from the SLE patient (positive control) that had been stored for 2 years at 280°C.…”

“…We showed that late-uveitis TINU was clinically and pathologically indistinguishable from DATIN at biopsy. We previously reported that mCRP-Ab might be useful in distinguishing patients with TINU from patients with DATIN (21). In this study, of patients diagnosed with DATIN, those who went on to develop late-onset uveitis (i.e., TINU misclassified as DATIN), had higher levels of mCRP-Ab compared with those who had true DATIN.…”

“…Autoantibodies against modified CRP (mCRP-Ab) were detected by ELISA as previously described (21). For each sample, the binding of the tested serum was expressed as the percentage of a known positive control serum.…”

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

“…We have previously regarded anti-CRP antibodies as rather specific for SLE, but this study and others clearly show that this does not hold true [16,36,37]. On the other hand, SLE and chronic HCV infection share several disease characteristics.…”

Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis

“…Accordingly, mCRP has been detected on circulating microparticles [81] and the discovery of RNA aptamers specifically recognizing mCRP [85] may eventually result in the development of clinical assays for mCRP. Alternatively, autoantibodies against mCRP that were found to be correlated with autoimmune [86][87][88] and heart diseases [89] could be regarded as an indirect index to measure global mCRP production.…”