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.
- lupus erythematosus
Data availability statement
Data are available upon reasonable request. All data including deidentified patient data,flow cytometry files and R code are available upon reasonable request from Dr Ignacio Sanz, email@example.com.
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CD and IS are joint senior authors.
Handling editor Josef S Smolen
SAJ and CW contributed equally.
Contributors All authors contributed to this work and approved of the final manuscript. Specific areas of contribution are listed below. Study conceptualisation was done by IS, CD, SAJ, CW and SL. IS, CD, SAJ, CW, SL and GB helped in study design. Data analysis was done by SAJ, CW, MCW, GB, RB and KC. RB, AH, KC, XW and FMR performed experiments. Clinical evaluation and patient recruitment were done by CD, LDA and SL. Drafting and revisions were performed by IS, CD, SAJ, CW, MCW and KC.
Funding This work was supported by the Centers for Disease Control and Prevention, (CDC) grant U01DP005119, National Institute of Health grants R37-AI049660 and Autoimmune Centre for Excellence U19AI110483-06 and the Georgia Research Alliance.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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