1. B cell subset composition segments clinically and serologically distinct groups in chronic cutaneous lupus erythematosus.
- Author
-
Jenks SA, Wei C, Bugrovsky R, Hill A, Wang X, Rossi FM, Cashman K, Woodruff MC, Aspey LD, Lim SS, Bao G, Drenkard C, and Sanz I
- Subjects
- Adult, Antibodies, Antinuclear, Autoantibodies immunology, Chromatin immunology, Chronic Disease, DNA immunology, Female, Flow Cytometry, Humans, Immunologic Memory immunology, Immunophenotyping, Lupus Erythematosus, Cutaneous complications, Lupus Erythematosus, Systemic complications, Male, Middle Aged, RNA immunology, RNA-Binding Proteins immunology, B-Lymphocyte Subsets immunology, B-Lymphocytes immunology, Lupus Erythematosus, Cutaneous immunology, Lupus Erythematosus, Systemic immunology
- Abstract
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.)
- Published
- 2021
- Full Text
- View/download PDF