Objective

B-cells are present in the inflamed arteries of giant cell arteritis (GCA) patients and a disturbed B-cell homeostasis is reported in peripheral blood of both GCA and the overlapping disease polymyalgia rheumatica (PMR). In this study, we aimed to investigate chemokine-chemokine receptor axes governing the migration of B-cells in GCA and PMR.

Methods

We performed Luminex screening assay for serum levels of B-cell related chemokines in treatment-naïve GCA (n = 41), PMR (n = 31) and age- and sex matched healthy controls (HC, n = 34). Expression of chemokine receptors on circulating B-cell subsets were investigated by flow cytometry. Immunohistochemistry was performed on GCA temporal artery (n = 14) and aorta (n = 10) and on atherosclerosis aorta (n = 10) tissue.

Results

The chemokines CXCL9 and CXCL13 were significantly increased in the circulation of treatment-naïve GCA and PMR patients. CXCL13 increased even further after three months of glucocorticoid treatment. At baseline CXCL13 correlated with disease activity markers. Peripheral CXCR3+ and CXCR5+ switched memory B-cells were significantly reduced in both patient groups and correlated inversely with their complementary chemokines CXCL9 and CXCL13. At the arterial lesions in GCA, CXCR3+ and CXCR5+ B-cells were observed in areas with high CXCL9 and CXCL13 expression.

Conclusion

Changes in systemic and local chemokine and chemokine receptor pathways related to B-cell migration were observed in GCA and PMR mainly in the CXCL9-CXCR3 and CXCL13-CXCR5 axes. These changes can contribute to homing and organization of B-cells in the vessel wall and provide further evidence for an active involvement of B-cells in GCA and PMR.

中文翻译：

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CXCL9-CXCR3 和 CXCL13-CXCR5 轴与巨细胞动脉炎和风湿性多肌痛中 B 细胞运输的关联

客观的

B 细胞存在于巨细胞动脉炎 (GCA) 患者的发炎动脉中，据报道，在 GCA 和重叠疾病风湿性多肌痛 (PMR) 的外周血中 B 细胞稳态紊乱。在这项研究中，我们旨在研究控制 GCA 和 PMR 中 B 细胞迁移的趋化因子-趋化因子受体轴。

方法

我们对未经治疗的 GCA (n = 41)、PMR (n = 31) 和年龄和性别匹配的健康对照 (HC, n = 34) 中 B 细胞相关趋化因子的血清水平进行了 Luminex 筛选测定。通过流式细胞术研究了循环 B 细胞亚群上趋化因子受体的表达。对 GCA 颞动脉 (n = 14) 和主动脉 (n = 10) 以及动脉粥样硬化主动脉 (n = 10) 组织进行免疫组织化学。

结果

趋化因子 CXCL9 和 CXCL13 在未经治疗的 GCA 和 PMR 患者的循环中显着增加。在糖皮质激素治疗三个月后，CXCL13 甚至进一步增加。在基线 CXCL13 与疾病活动标志物相关。两组患者的外周 CXCR3+ 和 CXCR5+ 转换记忆 B 细胞均显着减少，并且与它们的互补趋化因子 CXCL9 和 CXCL13 呈负相关。在 GCA 的动脉病变处，CXCL9 和 CXCL13 高表达区域观察到 CXCR3+ 和 CXCR5+ B 细胞。

结论

在 GCA 和 PMR 中主要在 CXCL9-CXCR3 和 CXCL13-CXCR5 轴中观察到与 B 细胞迁移相关的全身和局部趋化因子和趋化因子受体途径的变化。这些变化有助于 B 细胞在血管壁中归巢和组织，并为 B 细胞积极参与 GCA 和 PMR 提供进一步的证据。