Anti-carbamylated protein antibodies in systemic lupus erythematosus patients with articular involvement

Abstract

Objective Several studies have evaluated the prevalence of rheumatoid factor (RF) and anti-citrullinated proteins antibodies (ACPA) in systemic lupus erythematosus (SLE) patients but no data are available on the anti-carbamylated proteins (anti-CarP), a new biomarker for rheumatoid arthritis (RA). We evaluated the anti-CarP prevalence in SLE patients with joint involvement and the associations with different phenotypes. Methods Seventy-eight SLE patients with joint involvement were enrolled (F/M 73/5; mean ± SD age 47.6 ± 11.2 years; mean ± SD disease duration 214.3 ± 115.6 months). As control groups, we evaluated SLE patients without joint manifestations ( N = 15), RA ( N = 78) and healthy individuals (HS, N = 98). Anti-CarP were assessed by home-made ELISA in all patients and controls, RF and ACPA in SLE patients with joint involvement (commercial ELISA kit). Results The prevalence of anti-CarP in SLE patients with joint involvement was similar to RA ( p = NS) and significantly higher compared with SLE without joint involvement and HS ( p < 0.0001, p < 0.0001, respectively). Four patients were positive for all three antibodies: seventy-five percent of these showed Jaccoud arthropathy. Fourty-five percent of ACPA-ve/RF-ve patients were anti-CarP + ve. Conclusions The evaluation of anti-CarP in SLE joint involvement demonstrated a prevalence of almost 50%, similar to RA and significantly higher than SLE without joint involvement and HS

Anti-carbamylated protein antibodies and skin involvement in patients with systemic sclerosis: An intriguing association

“…This observation contrasts, however, with reports of high levels of anti-CarP Ab in rheumatic disorders, including RA [19,31,40,41], systemic lupus erythematosus (SLE) [42,43], and Sjögren’s syndrome [44]. In these studies, Ab levels associated with disease activity (in RA [19], SLE[42,43] and Sjögren's syndrome [44]) and with bone erosion (in RA [45–47]), and were predictive of RA onset in anti-CCP-positive patients with arthralgia without arthritis [48]. The postulated mechanism underlying these findings is that anti-CarP Ab levels increase concomitantly to the increase in carbamylated protein triggered by inflammation caused by the disease [19,44].…”

Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemic lupus erythematosus

“…We previously identified anti-CarP in 46.1% of patients with SLE with joint involvement, a prevalence matching that in patients with RA and significantly higher than that in healthy controls (2.4%). We also found that anti-CarP-positive patients were significantly more frequent than ACPA-positive patients [ 20 ].…”

“…Paralleling ACPA behavior, anti-CarP could induce the production of pro-inflammatory cytokines, leading to a more active phenotype. Nonetheless, anti-CarP seem specifically involved in joint involvement development rather than being markers of disease activity, since they do not correlate with disease activity indices, such as the SLEDAI-2 k. We may hypothesize that NETosis-derived myeloperoxidase could locally determine a pro-carbamylation milieu, leading to the break of immune tolerance and to the production of antibodies directed against carbamylated proteins [ 20 ]. NETosis, the specific neutrophil death, plays a fundamental role in SLE pathogenesis: several data have shown increased NETosis in patients with SLE, which significantly correlated with disease activity [ 35 ].…”

“…To date, only a few studies have analyzed the prevalence of anti-CarP in patients with SLE with joint involvement [ 18 – 20 ]. Thus, in the present cross-sectional study, we aimed at assessing the association between anti-CarP and US-detected erosive damage in a large cohort of patients with SLE with joint involvement.…”

An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders

“…Moreover, the association between anti-CarP antibodies and SLE has recently been assessed in large cohort studies of SLE patients with and without articular involvement; the findings showed a 50% prevalence of anti-CarP antibodies in SLE with joint involvement, which is higher than in patients without joint involvement [292]. A few recent studies have been considered with the anti-CarP antibodies and their significance in SLE with erosive phenotypes.…”