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AB0033 B regulatory cells positively correlate with antibodies against ss-a ro52 in systemic sclerosis

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Background We and Japanese Investigators have shown that IL-10-producing regulatory B cells (B10 cells) are decreased in systemic sclerosis (SSc).1 2 Contrary to the Japanese, we did not find a… Click to show full abstract

Background We and Japanese Investigators have shown that IL-10-producing regulatory B cells (B10 cells) are decreased in systemic sclerosis (SSc).1 2 Contrary to the Japanese, we did not find a negative correlation between B10 cells and SSc-specific autoantibodies (autoabs) against centromere, Scl-70 or RNA polymerase III.3 Since we found anti-Ro52 SS-A antibodies in approx. 30% of patients with SSc,4 this being the 3rd most frequent autoantibody in this disease, we considered what is the relation of B10 cells with anti-Ro52 antibodies. Objectives We examined the number and function of Bregs in SSc in relation to anti-Ro52 autoabs. Methods Serum samples and PBMCs were collected from 40 SSc patients (15 anti-Scl-70, 20 anti-CEN and 5 anti-RNA pol III) and were further divided according to anti-Ro52-positivity into 22 anti-Ro52(+) and 18 anti-Ro52 (-). All serum samples were tested for the presence of disease-specific autoantibodies against Scl-70, CENP, RNA-pol, and against Ro52 using a line assay (Euroimmun Germany). The function of Bregs was determined by the ability to express IL-10 following activation with ODN 2006 (TLR-9). Percentages of transitional (CD19 +CD24highCD38high) and memory (CD19 +CD27+CD24 high) Bregs were assessed by flow cytometry using fluorochrome conjugated antibodies (BD Biosciences). Results IL-10(+) Bregs (B10) were significantly elevated in SSc patients (6.7%±2.6% n=15) with high-titre antibodies against Ro52 (mean anti-Ro52 arbitrary units AU >100; positivity cut-off AU >20) compared to patients (4.2%±1.9%, n=22) totally negative for Ro52 (mean AU <10) (p=0.03). Transitional Bregs were also significantly increased in all SSc patients tested positive for anti-Ro52 autoantibodies (7.5%±1.9%) compared to SSc patients negative for anti-Ro52 autoantibodies (3.7±0.8, p=0.02). Furthermore, transitional Bregs positively correlated with anti-Ro52 antibody levels (r2=0.39 p=0.01). In contrast, memory Bregs were not significantly different between anti-Ro52-positive (14.1%±2.7%) and -negative SSc patients (11.8%±2.2%) (p>0.05). Conclusions IL10-producing Bregs are higher in SSc patients with high anti-Ro52 antibodies and transitional Bregs correlated with antiRo52 antibodies in patients with SSc suggesting that this autoantibody could be a potential marker of Breg efficiency. References [1] Mavropoulos A, et al. Arthritis Rheumatol2016;68(2):494–504. [2] Matsushita T, et al. Rheumatology2016;55(2):263–67. [3] Mavropoulos A, et al. Clin Immunol2017;184:26–32. [4] Liaskos C, et al. Autoimmunity2017;50(7):414–421. Disclosure of Interest None declared

Keywords: bregs; ro52; ssc patients; anti ro52

Journal Title: Annals of the Rheumatic Diseases
Year Published: 2018

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