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

• Published in: Annals of the rheumatic diseases Vol. 80; no. 9; pp. 1190 - 1200
• Main Authors: Jenks, Scott A, Wei, Chungwen, Bugrovsky, Regina, Hill, Aisha, Wang, Xiaoqian, Rossi, Francesca M, Cashman, Kevin, Woodruff, Matthew C, Aspey, Laura D, Lim, S. Sam, Bao, Gaobin, Drenkard, Cristina, Sanz, Ignacio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01.09.2021
• Subjects: Adult; Antibodies; Antibodies, Antinuclear; Autoantibodies; Autoantibodies - immunology; B-Lymphocyte Subsets - immunology; B-Lymphocytes - immunology; Chromatin; Chromatin - immunology; Chronic Disease; Cutaneous Lupus Erythematosus; DNA - immunology; Effector cells; Enzyme-linked immunosorbent assay; Female; Flow Cytometry; Genotype & phenotype; Homeostasis; Humans; Immunoglobulin G; Immunologic Memory - immunology; Immunological memory; Immunological tolerance; Immunophenotyping; Immunoprecipitation; Lupus; Lupus Erythematosus, Cutaneous - complications; Lupus Erythematosus, Cutaneous - immunology; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - immunology; Lymphocytes B; Male; Medical research; Memory cells; Middle Aged; Patients; RNA - immunology; RNA-binding protein; RNA-Binding Proteins - immunology; Serology; Skin diseases; Skin lesions; Statistical analysis; Systemic lupus erythematosus; systemic; B-lymphocytes; autoimmunity; lupus erythematosus; autoantibodies
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2021-220349

ObjectiveWhile 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.MethodsB-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.ResultsPatients 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.ConclusionCCLE 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.