Immunoglobulin Binding Protein 1 as a Potential Urine Biomarker in Patients with Lupus Nephritis

• Published in: International journal of molecular sciences 2019-05, Vol.20 (10), p.2606
• Main Authors: Lee, Eun-Ju, Kwon, Oh Chan, Ghang, Byeongzu, Lim, Doo-Ho, Kim, Do Hoon, Hong, Seokchan, Lee, Chang-Keun, Yoo, Bin, Kim, Yong-Gil
• Format: Article
• Language: English
• Subjects: Albumin; Albumins; Biomarkers; CXCL16 protein; Cyclic AMP response element-binding protein; Disease; disease activity; Genome-wide association studies; Genomes; immunoglobulin binding protein 1; Immunoglobulins; Immunological tolerance; Inflammation; Kinases; Laboratories; Lupus; Lupus nephritis; Lymphocytes; Lymphocytes T; Medical research; Nephritis; P-selectin; Phenotypes; Phosphatase; Proteins; Proteinuria; renal tubular epithelial cells; Systemic lupus erythematosus; Tumor necrosis factor receptors; TWEAK protein; Urine; urine biomarker; Vascular cell adhesion molecule 1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20102606

We evaluated the role of immunoglobulin binding protein 1 (IGBP1), a phosphoprotein associated with the B cell receptor (BCR) complex, as a urine biomarker in lupus nephritis (LN). The IGBP1 concentrations in plasma and urine of patients with LN, systemic lupus erythematosus (SLE) without nephritis and healthy controls were estimated by ELISA. IGBP1 expression in the kidneys of LN patients and transplantation donors was detected by immunohistochemistry. Microarray-based global gene expression profile of HK-2 cells with knock-down and fluorescence-activated cell sorting (FACS) for intracellular IGBP1 expression in human peripheral blood mononuclear cells (PBMCs) was performed. Urine IGBP1 levels were elevated significantly in LN patients, and it correlated with the clinical activity indices (complement 3 (C3) level, anti-dsDNA antibodies titer, SLE Disease Activity Index-2000 (SLEDAI-2K) and histological activity index. IGBP1 expression was increased in LN patients as compared to the donors and was detected mainly in the tubules by histopathology. In microarray analysis, several genes related to SLE pathogenesis ( , , , , , , and ) responded to siRNA-mediated silencing. In FACS, IGBP1 was expressed mainly in the CD14 cells. The overall expression of IGBP1 in PBMCs was higher in LN patients as compared with that in SLE patients without nephritis. Conclusively, urinary IGBP1 may be a novel biomarker reflecting the clinical and histological activities in LN.