Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.
Clin Exp Immunol. 2023 Jul 5;213(1):125-137. doi: 10.1093/cei/uxad024.
To investigate the features of circulating B cells, their expressing receptors, serum levels of B-cell activation factor of the TNF family (BAFF), and a proliferation-inducing ligand (APRIL) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Blood samples from 24 patients with active AAV (a-AAV), 13 with inactive AAV (i-AAV), and 19 healthy controls (HC) were included in this study. The proportion of B cells and their expressing BAFF receptor (BAFF-R), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation antigen were analyzed via flow cytometry. Serum levels of BAFF, APRIL, and interleukin (IL)-4, IL-6, IL-10, and IL-13 were also evaluated using an enzyme-linked immunosorbent assay. The proportion of plasmablasts (PB)/plasma cells (PC) and serum levels of BAFF, APRIL, IL-4, and IL-6 were significantly higher in a-AAV than in HC. Higher serum levels of BAFF, APRIL, and IL-4 were observed in i-AAV than in HC. Lower expression of BAFF-R on memory B cells and higher expression of TACI on CD19+ cells, immature B cells, and PB/PC were demonstrated in a-AAV and i-AAV than in HC. The population of memory B cells was positively associated with serum APRIL levels and BAFF-R expression in a-AAV. In conclusion, decreased expression of BAFF-R on memory B cells and increased expression of TACI on CD19+ cells, immature B cells, and PB/PC, as well as increased serum levels of BAFF and APRIL, were sustained even in the remission phase of AAV. Persistent aberrant signaling of BAFF/APRIL may contribute to disease relapse.
为了研究抗中性粒细胞胞浆抗体相关性血管炎（AAV）患者循环 B 细胞及其表达的受体、肿瘤坏死因子家族 B 细胞激活因子（BAFF）和增殖诱导配体（APRIL）的特征。本研究纳入了 24 例活动期 AAV（a-AAV）、13 例缓解期 AAV（i-AAV）和 19 例健康对照（HC）的血液样本。采用流式细胞术分析 B 细胞及其表达的 BAFF 受体（BAFF-R）、跨膜激活剂和钙调节剂及环孢素配体相互作用蛋白（TACI）、B 细胞成熟抗原的比例。采用酶联免疫吸附试验检测血清 BAFF、APRIL、白细胞介素（IL）-4、IL-6、IL-10 和 IL-13 的水平。a-AAV 患者的浆母细胞/浆细胞（PB/PC）比例及血清 BAFF、APRIL、IL-4 和 IL-6 水平显著高于 HC。i-AAV 患者的血清 BAFF、APRIL 和 IL-4 水平高于 HC。与 HC 相比，a-AAV 和 i-AAV 患者记忆 B 细胞上的 BAFF-R 表达降低，CD19+细胞、未成熟 B 细胞和 PB/PC 上的 TACI 表达增加。a-AAV 患者中记忆 B 细胞的数量与血清 APRIL 水平和 BAFF-R 表达呈正相关。结论：即使在 AAV 缓解期，记忆 B 细胞上 BAFF-R 的表达降低，CD19+细胞、未成熟 B 细胞和 PB/PC 上的 TACI 表达增加，以及血清 BAFF 和 APRIL 水平升高，仍然持续存在。BAFF/APRIL 的异常信号持续存在可能导致疾病复发。
