T cells are central to the pathogenesis of lupus nephritis (LN), a common complication of systemic lupus erythematosus (SLE). CD6 and its ligand, activated leukocyte cell adhesion molecule (ALCAM), are involved in T cell activation and trafficking. Previously, we showed that soluble ALCAM is increased in urine (uALCAM) of patients with LN, suggesting that this pathway contributes to disease. To investigate, uALCAM was examined in 1038 patients with SLE and LN from 5 ethnically diverse cohorts; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of SLE and acute glomerulonephritis. Extended cohort analysis offered resounding validation of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells whereas CD6 expression was exclusive to T cells, with elevated numbers of CD6⁺ and ALCAM⁺ cells in patients with LN. CD6 blockade in models of spontaneous lupus and immune-complex glomerulonephritis revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data demonstrate the contribution of the CD6/ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target.

中文翻译：

---

CD6/ALCAM 通路通过 T 细胞介导的反应促进狼疮性肾炎

T 细胞是狼疮肾炎 (LN) 发病机制的核心，这是系统性红斑狼疮 (SLE) 的常见并发症。CD6 及其配体，活化的白细胞粘附分子 (ALCAM)，参与 T 细胞的活化和运输。以前，我们发现 LN 患者尿液中的可溶性 ALCAM (uALCAM) 增加，表明该途径导致疾病。为了进行调查，对来自 5 个种族不同的队列的 1038 名 SLE 和 LN 患者进行了 uALCAM 检测；在 LN 肾细胞中评估了 CD6 和 ALCAM 的表达；在 SLE 和急性肾小球肾炎的小鼠模型中，通过抗体阻断 CD6 来测试疾病的贡献。扩展队列分析提供了对 uALCAM 作为区分 SLE 中活动性肾脏受累的生物标志物的有力验证，而与种族无关。LN 患者的⁺和 ALCAM ^+细胞。自发性狼疮和免疫复合物肾小球肾炎模型中的 CD6 阻断显示免疫细胞、炎症标志物和疾病测量值显着减少。我们的数据证明了 CD6/ALCAM 通路对 LN 和 SLE 的贡献，支持其用作疾病生物标志物和治疗靶点。