Abstract
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 IGBP1 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 (PPME1, ROCK2, VTCN1, IL-17R, NEU1, HLA-DM, and PTX3) responded to siRNA-mediated IGBP1 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.
Highlights
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production, immune complex deposition, and end-organ damage
This phosphoprotein of the B cell receptor (BCR) complex correlated with several indices including SLEDAI-2K, levels of complement 3 (C3) and anti-dsDNA antibodies titers suggesting SLE activity
Renal histological analysis showed that Immunoglobulin binding protein 1 (IGBP1) expression was predominant in tubular lesions, which correlated to the histological activity
Summary
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production, immune complex deposition, and end-organ damage. Lupus nephritis (LN) is the most common and serious complication of SLE. 10 to 15% of LN patients progress to end-stage renal disease, and the 5-year survival rate of LN patients is stalled at 82%, whereas the 5-year survival for SLE patients without nephritis is 92% [1]. Histological examination of the kidney is a valuable tool for the diagnosis, assessment, and prognostication of SLE patients. A kidney biopsy can be accompanied by significant morbidity and cannot usually be performed serially. A non-invasive, obtainable, and accurate marker that can be followed serially may, be of great value in monitoring LN patients [2,3]. Laboratory markers in current use, including serological determination of serum anti-double-stranded (ds)DNA antibodies and complement levels can be helpful clinically, the correlation between these and LN is weak [4]
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