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

Autor: Jenks SA; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.; Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA., Wei C; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.; Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA., Bugrovsky R; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.; Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA., Hill A; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.; Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA., Wang X; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.; Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA., Rossi FM; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.; Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA., Cashman K; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.; Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA., Woodruff MC; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.; Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA., Aspey LD; Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA., Lim SS; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA., Bao G; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA., Drenkard C; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA., Sanz I; Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA ignacio.sanz@emory.edu.; Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA.
Jazyk: angličtina
Zdroj: Annals of the rheumatic diseases [Ann Rheum Dis] 2021 Sep; Vol. 80 (9), pp. 1190-1200. Date of Electronic Publication: 2021 Jun 03.
DOI: 10.1136/annrheumdis-2021-220349
Abstrakt: Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze: MEDLINE