Prognostic value of anti-CRP antibodies in lupus nephritis in long-term follow-up

Background: Autoantibodies against monomeric C-reactive protein (anti-CRP-Ab) observed in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) were suggested to be associated with active LN and a poor response to therapy during short-term follow-up. The aim of this study was to confirm this finding and to investigate the prognostic value of anti-CRP-Ab in patients with LN during long-term follow-up. Methods: Sera of 57 SLE patients (47 women, 10 men) with biopsy proven LN and 122 healthy individuals were analyzed for the presence of anti-CRP-Ab by in-house ELISA. Anti-CRP-Ab levels were studied in relation to routine laboratory tests, urine analysis, levels of C3, C4, other immunological markers and the overall disease activity as assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The prognostic value of anti-CRP-Ab was tested in a subgroup of 29 newly diagnosed LN patients (median follow-up 5.9 years). Response to therapy at various time points was assessed with respect to baseline anti-CRP-Ab levels. At least partial response in the first/second year of treatment was considered as a favorable outcome, while non-response, renal flare or end stage renal disease were considered as unfavorable outcome. Results: Anti-CRP-Ab were only detected in patients with active renal disease and their levels correlated with SLEDAI (r(s) = 0.165, p = 0.002). The time to response was shorter in patients being anti-CRP-Ab negative at baseline compared to anti-CRP-Ab positive patients, p = 0.037. In the second year of therapy, baseline anti-CRP-Ab positivity was a significant predictor of unfavorable outcome (OR [95 % CI] = 15.6 [1.2-771]; p = 0.021). The predictive value of baseline anti-CRP positivity further increased when combined with non-response to therapy in the first year. Baseline anti-CRP-Ab positivity was not a predictor of unfavorable outcome at the end of follow-up, (OR [95 % CI] = 5.5 [0.6-71.1], p = 0.169). Conclusions: Baseline serum levels of anti-CRP-Ab seem to be a strong risk factor for a composite outcome of non-response, renal flare or end stage renal disease after two years of standard treatment of LN. The response to therapy seems to be delayed in anti-CRP-Ab positive patients.