Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Streptoccocal infections can cause rheumatic fever sharing clinical presentations similar to SLE. Whether oral commensal streptococci could induce cross-reactive and pathogenic antibodies remained unknown. So we aimed to search for novel biomarkers in SLE through cross-reactive antibody repertoire screening, and we investigated to find specific antibodies presented in the serum of lupus patients.
Methods: The streptococcal L7/L12 ribosomal protein(RP-L7/L12) was identified through serum antibody-screening assay in SLE patient with higher disease activity followed by a proteomic approach. Recombinant RP-L7/L12 was purified and serum antibody levels were detected by ELISA quantitatively. The biomarkers of kidney impairment associated with SLE such as UPCR(urine protein to creatinine ratio), serum complement component 3(C3) and Anti-dsDNA were test serially too.
Results: A total of 25 lupus patients were enrolled from Jan, 2016 to May, 2018, with diagnosis of systemic lupus erythematosus according to The Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria, were to receive rituximab (500 mg) on days 1, 15, 168(Week24), and 182. The primary end point was UPCR result at day 336(Week48). Patients (N=14/25, 56%) respond to rituximab therapy (decrease of UPCR compared to baseline UPCR(baseline mean:1.97 ±2.84 mg/mg; Day336(Week48) Mean: 0.44±0.58), and the overall improvement of UPCR is significant (p=0.01 (Wilcoxon signed-rank test)); The concomitant increase of C3(70.9 ±28.1 mg/dL; Week48: 85.19±23.54mg/dL, p=0.004), decreasing Anti-dsDNA(192.11±203.48; Week48:107.30±101.19 WHO units/mL, p=0.0025 ), and steroid sparing effect(prednisolone equivalent: 15.70 ±9.47 mg/day; Week48 mean: 10.20±6.08, p=0.0032 ) were also noted. The mean SELENA-SLEDAI scores (systemic lupus erythematosus disease activity index SELENA modification) was higher in the response group. Higher anti-RP L7/L12 antibody titres(0.72+/-0.35(SLE- glomerulonephritis(GN)) vs 0.52+/-0.33(p=0.09)) in patients with SLE is associated with higher rate of GN(proteinuria>=0.5gm/day.) An average 76.0% decrease of anti-RP-L7/L12 titre after a 24-week interval were detected in patients of SLE(N=15) receiving rituximab. Another three patients with SLE had two-fold increase in anti-RP-L7/L12 after rituximab, probably indicative of disease flare. The Pearson correlation coefficient was calculated between the dynamics of anti-RP-L7/L12(baseline/12/24-week) and the dynamics of UPCR change, a moderate positive correlation was observed (R2=0.3367.)
Conclusion: Higher streptococcal anti-RP L7/L12 antibody in SLE is associated with higher rate of glomerulonephritis. The novel antibody against commensal bacterial antigen is predictive of the response of rituximab in SLE. Further identification of human cross-reactive antigens were underway.
To cite this abstract in AMA style:Kuo YM, Chen J, Chia JS, Jung CJ, Hsieh SC. Novel Antibody Against Commensal Bacterial Antigen in Prediction of the Response of Rituximab in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/novel-antibody-against-commensal-bacterial-antigen-in-prediction-of-the-response-of-rituximab-in-systemic-lupus-erythematosus/. Accessed July 2, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/novel-antibody-against-commensal-bacterial-antigen-in-prediction-of-the-response-of-rituximab-in-systemic-lupus-erythematosus/