B cell subset composition segments clinically and serologically distinct groups in chronic cutaneous lupus erythematosus

• Authors: Scott Jenks, Emory University; Chungwen Wei, Emory University; Regina Bugrovsky, Emory University; Aisha Hill, Emory University; Xiaoqian Wang, Emory University; Francesca M Rossi, Emory University; Kevin Cashman, Emory University; Matthew Woodruff, Emory University; Laura Aspey, Emory University; Sung Lim, Emory University; Gaobin Bao, Emory University; Cristina Drenkard, Emory University; Ignacio Sanz, Emory University
• Journal Title: ANNALS OF THE RHEUMATIC DISEASES
• Volume: Volume 80, Number 9
• Publisher: BMJ PUBLISHING GROUP | 2021-09-01, Pages 1190-1200
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1136/annrheumdis-2021-220349
• Subjects: Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Rheumatology; DISEASE-ACTIVITY; SEVERITY INDEX; T-CELL; ANTIBODIES; AUTOANTIBODIES; AUTOREACTIVITY; POPULATION; EXPRESSION; BLOOD; ONSET

Abstract

While the contribution of B-cells to SLE is well established, its role in chronic cutaneous lupus erythematosus (CCLE) remains unclear. Here, we compare B-cell and serum auto-antibody profiles between patients with systemic lupus erythematosus (SLE), CCLE, and overlap conditions. B-cells were compared by flow cytometry amongst healthy controls, CCLE without systemic lupus (CCLE+/SLE−) and SLE patients with (SLE+/CCLE+) or without CCLE (SLE+/CCLE−). Serum was analyed for autoreactive 9G4+, anti-double-stranded DNA, anti-chromatin and anti-RNA antibodies by ELISA and for anti-RNA binding proteins (RBP) by luciferase immunoprecipitation. Patients with CCLE+/SLE− share B-cell abnormalities with SLE including decreased unswitched memory and increased effector B-cells albeit at a lower level than SLE patients. Similarly, both SLE and CCLE+/SLE- patients have elevated 9G4+ IgG autoantibodies despite lower levels of anti-nucleic acid and anti-RBP antibodies in CCLE+/SLE−. CCLE+/SLE− patients could be stratified into those with SLE-like B-cell profiles and a separate group with normal B-cell profiles. The former group was more serologically active and more likely to have disseminated skin lesions. CCLE displays perturbations in B-cell homeostasis and partial B-cell tolerance breakdown. Our study demonstrates that this entity is immunologically heterogeneous and includes a disease segment whose B-cell compartment resembles SLE and is clinically associated with enhanced serological activity and more extensive skin disease. This picture suggests that SLE-like B-cell changes in primary CCLE may help identify patients at risk for subsequent development of SLE. B-cell profiling in CCLE might also indentify candidates who would benefit from B-cell targeted therapies.