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B 细胞亚群组成将慢性皮肤红斑狼疮中的临床和血清学上不同的群体分段。

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

机构信息

Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA.

Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA.

出版信息

Ann Rheum Dis. 2021 Sep;80(9):1190-1200. doi: 10.1136/annrheumdis-2021-220349. Epub 2021 Jun 3.

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.

摘要

目的

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。

方法

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)。

结果

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。

结论

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。

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