Teymur Aygun, Tang Chenling, Nazir Fariz, Ostadnejad Neda, Cai Qi, Saxena Ramesh, Wu Tianfu
University of Houston, Houston, Texas.
University of Texas Southwestern Medical Center, Dallas.
ACR Open Rheumatol. 2025 May;7(5):e70044. doi: 10.1002/acr2.70044.
This study aims to investigate whether V-set Ig domain-containing protein 4 (VSIG4; also known as complement receptor of the Ig superfamily [CRIg]) forms immune complexes (ICxs) with IgG and complement component 3 (C3) in the kidneys of patients with lupus nephritis (LN) and to assess the potential of urinary VSIG4 and VSIG4-ICx as noninvasive biomarkers of LN.
Immunofluorescent staining was employed to detect the deposition of VSIG4 (CRIg), IgG, and C3 in kidney tissue. Urine samples from 102 patients with LN, 51 healthy controls (HCs), and 13 patients with chronic kidney disease (CKD) were analyzed via enzyme-linked immunosorbent assay for VSIG4-ICx and free-form VSIG4.
Immunofluorescence costaining demonstrated the colocalization of VSIG4, IgG, and C3 in the kidneys of those with LN and elevated VSIG4 protein expression in the glomeruli regions in LN. Compared with HCs and those with CKD, patients with LN exhibited significantly elevated levels of urinary VSIG4 in both free form and ICx. Urinary VSIG4-ICx correlated with clinical parameters, including the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (R = 0.55, P < 0.0001), renal SLEDAI (R = 0.52, P < 0.0001), estimated glomerular filtration rate (-0.5, P < 0.001), activity index (R = 0.25, P < 0.05), chronicity index (R = 0.32, P < 0.05), complement C3 (R = -0.33, P < 0.05), and complement C4 (R = -0.31, P < 0.05). The strong association of the urinary VSIG4-ICx with disease activity metrics and histopathologic evidence underscores its potential for clinical utility in diagnosing and monitoring LN.
VSIG4-ICx shows promise as a novel urine biomarker for LN, with potential utility for diagnosis and disease monitoring.
本研究旨在调查含V结构域免疫球蛋白4（VSIG4；也称为免疫球蛋白超家族补体受体[CRIg]）是否在狼疮性肾炎（LN）患者的肾脏中与IgG和补体成分3（C3）形成免疫复合物（ICx），并评估尿VSIG4和VSIG4-ICx作为LN非侵入性生物标志物的潜力。
采用免疫荧光染色检测肾脏组织中VSIG4（CRIg）、IgG和C3的沉积。通过酶联免疫吸附测定法分析了102例LN患者、51例健康对照（HC）和13例慢性肾脏病（CKD）患者的尿液样本中的VSIG4-ICx和游离形式的VSIG4。
免疫荧光共染色显示LN患者肾脏中VSIG4、IgG和C3共定位，且LN患者肾小球区域的VSIG4蛋白表达升高。与HC和CKD患者相比，LN患者游离形式和ICx形式的尿VSIG4水平均显著升高。尿VSIG4-ICx与临床参数相关，包括系统性红斑狼疮疾病活动指数（SLEDAI）（R = 0.55，P < 0.0001）、肾脏SLEDAI（R = 0.52，P < 0.0001）、估计肾小球滤过率（-0.5，P < 0.001）、活动指数（R = 0.25，P < 0.05）、慢性指数（R = 0.32，P < 0.05）、补体C3（R = -0.33，P < 0.05）和补体C4（R = -0.31，P < 0.05）。尿VSIG4-ICx与疾病活动指标和组织病理学证据的强关联突出了其在诊断和监测LN方面的临床应用潜力。
VSIG4-ICx有望成为LN的新型尿液生物标志物，具有诊断和疾病监测的潜在用途。
