We could not confirm anti-CRP-Ab as a significant predictor of unfavorable therapeutic outcome after 1?year of therapy (OR?=?1

We could not confirm anti-CRP-Ab as a significant predictor of unfavorable therapeutic outcome after 1?year of therapy (OR?=?1.8; anti-C-reactive protein antibodies, anti-C1q antibodies, glomerular filtration rate, high-sensitivity C-reactive protein, not significant, Systemic Lupus Erythematosus Disease Activity Index. 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 CA-074 Methyl Ester of treatment was considered as a favorable outcome, while nonresponse, 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 CA-074 Methyl Ester with SLEDAI (rs?=?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?% CA-074 Methyl Ester 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 nonresponse, 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. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0879-8) contains supplementary material, which is available to authorized users. Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease leading to the formation of a wide range of pathogenic autoantibodies and immune complexes. SLE mainly affects young women, with a clinically significant impact on morbidity and mortality. Renal involvement is among the most severe manifestations of SLE, which in its most aggressive forms can lead to Rabbit polyclonal to AMDHD1 renal failure. The pathogenesis of SLE is only partially understood. A number of potentially pathogenic autoantibodies have been described in SLE; for example, anti-double-stranded DNA antibodies (anti-dsDNA-Ab), anti-nucleosome antibodies, and anti-C1q antibodies CA-074 Methyl Ester (anti-C1q-Ab). Some of these correlate with SLE and/or lupus nephritis (LN) activity and are used in routine clinical practice for diagnostic purposes [1C7]. Pentameric C-reactive protein (CRP) under specific conditions dissociates irreversibly into monomers (mCRP) and reveals new epitopes [8C11]. The physiological function of mCRP includes opsonization, elimination of immune complexes, and clearance of apoptotic cells. This is achieved by the interaction of mCRP with C1q and complement factor H [12]. While other acute phase proteins increase in active SLE, levels of CRP usually remain low [13]. This might be caused by a suppression of interleukin (IL)-6-mediated CRP production in hepatocytes by overexpression of interferon alpha (IFN) [14] and by CRP gene polymorphisms [15]. Another mechanism could be an accelerated conversion of CRP into mCRP [16]. Antibodies interfering with the function of mCRP (such as IgG autoantibodies against mCRP (anti-CRP-Ab)) might lead to an altered clearance of apoptotic cells and be involved in pathogenic mechanisms of LN [12]. Interestingly, anti-CRP-Ab recognize the mCRP subunits, but not the native pentameric form of CRP, and thusas other lupus autoantibodiescan be considered neo-epitope specific [8]. A high prevalence of anti-CRP-Ab in SLE patients was described by Bell et al. [8]. Later, anti-CRP-Ab were shown to be associated with active LN [17C19] and renal tubulointerstitial lesions [18]. Some authors observed colocalization of IgG with CRP and other factors such as C1q and anti-dsDNA-Ab in the glomerular basement membrane and the renal subendothelial space in LN [20, 21]. Another study showed that levels of anti-CRP-Ab correlated with the renal biopsy activity index, as documented on repeated renal biopsies, and predicted a poor response to therapy during an 8-month follow-up [17]. The aim of our study was to determine whether baseline anti-CRP-Ab positivity predicts the long-term outcome in LN patients treated with standard therapy. Methods Study subjects A total of 57 patients (47 women, 10 men; median age 32.1?years) with definite SLE classified according to the American College of Rheumatology criteria [22] and biopsy-proven LN (29 new diagnoses of LN in.