Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.
Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA.
Ann Rheum Dis. 2021 Sep;80(9):1190-1200. doi: 10.1136/annrheumdis-2021-220349. Epub 2021 Jun 3.
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.
尽管 B 细胞对系统性红斑狼疮（SLE）的贡献已得到充分证实，但它在慢性皮肤型狼疮（CCLE）中的作用仍不清楚。在此，我们比较了 SLE、CCLE 和重叠疾病患者的 B 细胞和血清自身抗体谱。
通过流式细胞术比较健康对照组、无系统性红斑（CCLE+/SLE-）的 CCLE 患者以及有（SLE+/CCLE+）或无 CCLE（SLE+/CCLE-）的 SLE 患者之间的 B 细胞。通过 ELISA 分析血清中的自身反应性 9G4+、抗双链 DNA、抗染色质和抗 RNA 抗体，通过荧光素酶免疫沉淀分析抗 RNA 结合蛋白（RBP）。
CCLE+/SLE-患者的 B 细胞异常与 SLE 患者相似，包括未转换的记忆 B 细胞减少和效应 B 细胞增加，尽管程度低于 SLE 患者。同样，SLE 和 CCLE+/SLE-患者均有升高的 9G4+IgG 自身抗体，尽管 CCLE+/SLE-中的抗核酸和抗 RBP 抗体水平较低。CCLE+/SLE-患者可分为具有 SLE 样 B 细胞特征的患者和具有正常 B 细胞特征的患者。前者的血清学活性更高，更有可能出现播散性皮肤病变。
CCLE 表现出 B 细胞稳态失调和部分 B 细胞耐受破坏。我们的研究表明，这种疾病在免疫学上具有异质性，包括一个疾病亚群，其 B 细胞群类似于 SLE，与增强的血清学活性和更广泛的皮肤疾病相关。这种情况表明，原发性 CCLE 中的 SLE 样 B 细胞改变可能有助于识别随后发生 SLE 的风险患者。CCLE 的 B 细胞分析也可能确定受益于 B 细胞靶向治疗的候选者。
