Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Systemic lupus erythematosus (SLE) is a severe systemic autoimmune disease characterized by immune-complexes (ICx) which cause inflammation and damage. Effective targeting of autoantibody secreting cells could be key to reset autoimmunity. Functionally, SLE-specific ICx are important triggers of neutrophil extracellular trap (NET) formation. A consortium was formed to study B-cell targeted therapies, including RTX, Bortezomib (BTZ) or combination of RTX + Belimumab (BLM). The present study aimed to investigate the effects of these therapies on relevant autoantibody levels and excessive NET formation.
Methods: This study involved three cohorts of severe SLE patients that were eligible to experimental treatment with RTX (n=16), BTZ (n=12) or RTX+BLM (n=16). A cross-sectional cohort of 35 SLE patients served as a control cohort. A panel of SLE relevant autoantibodies against dsDNA, histones, nucleosomes and C1q were measured by ELISA. NET formation was quantified by a novel highly-sensitive assay using 3D confocal microscopy (Kraaij et al. 2016).
Results: Comparing three regimens, RTX+BLM resulted in the strongest significant reduction on anti-dsDNA, anti-Histone and anti-Nucleosomes antibodies compared to a smaller decrease by RTX and BTZ. Interestingly, RTX+BLM specifically decreased anti-C1q antibodies, which were not targeted by RTX or BTZ. ICx-mediated NET formation was only significantly decreased with a median of 75% [53 – 85%] after RTX+BLM (p=0.0002). Successful seroconversion of autoantibodies associated with decreased NET formation (p=0.02). The latter phenomenon was further corroborated in an independent cohort of SLE patients, where excessive NET formation associated with the presence of three or more autoantibody specificities (p=0.02), and specifically with the presence of anti-C1q antibodies (p=0.03).
Conclusion: In this reverse, translational study of B-cell targeted therapies, we demonstrate that anti-C1q autoantibodies were derived from Blys-dependent proliferating plasmablasts because they were only susceptible to RTX+BLM therapy. Moreover, therapeutically narrowing of the autoantibody repertoire decreased immune-complex mediated NET formation.
To cite this abstract in AMA style:van Dam L, Osmani Z, Kraaij T, Kamerling SWA, Bakker JA, Scherer HU, Rabelink T, Voll R, Isenberg DA, van Kooten C, Teng YKO. The Effect of B Cell Targeted Therapies on Autoantibodies and Excessive Neutrophil Extracellular Trap Formation in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/the-effect-of-b-cell-targeted-therapies-on-autoantibodies-and-excessive-neutrophil-extracellular-trap-formation-in-systemic-lupus-erythematosus/. Accessed August 14, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-b-cell-targeted-therapies-on-autoantibodies-and-excessive-neutrophil-extracellular-trap-formation-in-systemic-lupus-erythematosus/