Anti-nucleosome antibodies increase the risk of renal relapse in a prospective cohort of patients with clinically inactive systemic lupus erythematosus

Abstract

An important goal in the management of systemic lupus erythematosus (SLE) is the prediction of relapses. This study assesses whether anti-nucleosome antibodies (anti-NCS) increase the risk of renal relapse in inactive SLE. A prospective cohort of 115 patients with inactive SLE (M-SLEDAI ≤ 2) were followed for 12 months to assess the development of relapse (increase of M-SLEDAI ≥ 4) and specific renal flare (renal SLEDAI ≥ 4). At baseline, we identified potential risk factors for relapse, including anti-NCS. At baseline, 18 (16%) of the 115 patients with inactive SLE were anti-NCS positive. At the 12-month follow-up, anti-NCS-positive patients had a higher incidence of renal relapse compared to anti-NCS-negative patients (38.9% vs 13.4%, respectively). In Cox regression analysis, after adjusting for age, disease duration, anti-dsDNA, and immunosuppressive drugs, the presence of anti-NCS positivity at baseline increased the risk of renal relapse (HR: 5.31, 95% CI 2.03-13.92). Nevertheless, there were no differences in the incidence of other relapses in anti-NCS-positive versus anti-NCS-negative. Our results indicate that in inactive SLE, anti-NCS determination can be useful for identifying patients with a higher risk of developing renal relapse. Interestingly, this study identified that continued use of oral immunosuppressive therapy in patients with inactive SLE can reduce the risk of renal relapse. Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with different patterns of disease activity, including remission and episodes of relapse involving organs and tissues that produce a broad spectrum of clinical manifestations 1,2. Several studies have identified a rate of relapse in SLE varying from 62

A Perplexing Presentation of SLE as Adrenal Insufficiency in a Young Male

“…[ 1 ] Apart from the role of anti-dsDNA antibodies, nucleosome-specific antibodies, and nucleosome-anti-NCS antibody immune complex also play a significant role in the pathogenesis and disease progression. [ 4 5 ] Anti-NCS antibodies are more sensitive and specific for SLE than the anti-dsDNA antibodies and strongly correlate with renal damage, especially in patients of SLE lacking anti-dsDNA antibodies. [ 6 ] However, autoimmune mechanisms in SLE and AI may be common that could explain the possible coexistence.…”

“…Anti-NCS antibodies are part of a family of autoantibodies directed against histone epitope exposed in chromatin, which have a higher affinity for intact nucleosome; conformational epitope of the conjugation between dsDNA and the core histone. [ 4 ]…”

“…The prevalence of anti-NCS antibodies in SLE varies in various studies from 16 to 100%. [ 4 6 7 8 ] Studies which had low prevalence were mainly composed of patients of long disease duration on immune suppressive medications or in an inactive state of disease. On the other hand, higher prevalence studies mainly included patients with either active SLE disease or patients were assessed during major organ involvement like nephritis.…”

“…On the other hand, higher prevalence studies mainly included patients with either active SLE disease or patients were assessed during major organ involvement like nephritis. [ 4 ] A meta-analysis showed that anti-NCS antibodies have equal specificity (94.9% vs. 94.2%), but higher sensitivity (59.9% vs. 52.4%) and prognostic value than anti-dsDNA antibodies in the diagnosis of SLE. [ 9 ] A few reports described that anti-NCS antibodies are more sensitive and specific for SLE than the anti-dsDNA antibodies and also have a positive correlation with SLE disease activity index (SLEDAI) and with kidney damage.…”

Neutrophil Extracellular Traps-DNase Balance and Autoimmunity

“…Nucleosomes have been shown to be more strongly immunogenic than native DNA or histones, and induce a strong T-helper-cell response [28]. Moreover, antinucleosome antibodies were recently proposed as a marker to identify patients with a higher risk of developing renal relapse in inactive SLE [29,30]. It is largely recognized that the physical form and the length of DNA are directly correlated and may determine its antigenicity.…”