B-Cell Maturation Antigen (BCMA) as a Biomarker and Potential Treatment Target in Systemic Lupus Erythematosus

B细胞激活因子 贝里穆马布 免疫学 B细胞 流式细胞术 系统性红斑狼疮 医学 生物标志物 红斑狼疮 抗体 等离子体电池 生物 内科学 疾病 生物化学
作者
J. M. Martin,Qingyu Cheng,Sarah Laurent,Franziska S. Thaler,Anne Elisabeth Beenken,Edgar Meinl,Gerhard Krönke,Falk Hiepe,Tobias Alexander
出处
期刊:International Journal of Molecular Sciences [Multidisciplinary Digital Publishing Institute]
卷期号:25 (19): 10845-10845 被引量:10
标识
DOI:10.3390/ijms251910845
摘要

The BAFF-APRIL system is crucial for the pathogenesis of systemic lupus erythematosus (SLE) by promoting B cell survival, differentiation and the maintenance of humoral autoimmunity. Here, we investigated the relationship of BCMA expression on B cell subsets with its ligands BAFF and APRIL, together with soluble BCMA, and with clinical and serologic variables in a cohort of 100 SLE patients (86 under conventional and 14 under belimumab therapy) and 30 healthy controls (HCs) using multicolor flow cytometry and ELISA. We found that BCMA expression in SLE patients was significantly increased on all B cell subsets compared to HCs, with all examined components of the BAFF-APRIL system being upregulated. BCMA expression was significantly increased on switched and unswitched memory B cells compared to naïve B cells, both in HCs and SLE. BCMA expression on B cells correlated with plasmablast frequencies, serum anti-dsDNA antibodies and complement consumption, while soluble BCMA correlated with plasmablast frequency, highlighting its potential as a clinical biomarker. Belimumab treatment significantly reduced BCMA expression on most B cell subsets and soluble TACI and contributed to the inhibition of almost the entire BAFF-APRIL system and restoration of B cell homeostasis. These results provide insights into the complex dysregulation of the BAFF-APRIL system in SLE and highlight the therapeutic potential of targeting its components, particularly BCMA, in addition to its use as a biomarker for disease activity.
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