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

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.

Proteomic Analysis for Identification of Novel Urinary Biomarkers in Juvenile Systemic Lupus Erythematosus

“…In a previous study, 23 differential metabolites and 5 perturbed pathways including aminoacyl-tRNA biosynthesis, thiamine metabolism, nitrogen metabolism, tryptophan metabolism, and cyanoamino acid metabolism were identi ed between SLE patients and healthy controls [1]. Also, the studies exhibited that immunoglobulin binding protein [7], urinary vitamin D-binding protein and S100 calcium binding protein (S100) were the potential biomarkers in patients with lupus nephritis [11][12]. With signi cant advances in proteomic technologies, the comprehensive pro ling of protein expression in bio uids from patients with a given disease prompts a deep exploration of disease and its underlying mechanisms.…”

“…The changes in humoral metabolomics including serum, plasma, urine and sputum can provide abundant information on the physiological and pathological states of individuals and useful clinical parameters. Consequently, to understand the enormous potential in terms of revealing disease conditions will also bring the promise of a revolution in disease diagnosis and therapeutic monitoring [7][8][9][10]. In a previous study, 23 differential metabolites and 5 perturbed pathways including aminoacyl-tRNA biosynthesis, thiamine metabolism, nitrogen metabolism, tryptophan metabolism, and cyanoamino acid metabolism were identi ed between SLE patients and healthy controls [1].…”

Effect of Human Mesenchymal Stem Cells on Xenogeneic T and B Cells Isolated from Lupus-Prone MRL.Faslpr Mice

“…However, it is still unclear whether hMSCs inhibit mouse T and B cells in this xenogeneic animal model. Here, we addressed this issue and investigated the interaction between hMSCs and mouse B cells in detail, since B cells play a critical role in SLE pathogenesis [13]. We found that naïve hMSCs inhibited mouse T cells only, whereas priming of hMSCs with IFN-γ rendered them capable of inhibiting mouse B cells in a CXCL10-and IDO-dependent manner.…”

“…Systemic lupus erythematosus (SLE) is characterized by the production of autoantibodies to ubiquitous self-antigens [13]. In preclinical studies, the transfer of human MSCs (hMSCs) to lupus-prone MRL/MpJ-Fas lpr (called MRL.Fas lpr hereafter) mice increased their survival and decreased the anti-dsDNA antibody level and nephritis [14].…”

Value of monitoring urine ammonia at time of biopsy in patients with lupus nephritis

“…Proteinuria as the major candidate of urine presents a weak connection with the historical activity in LN and adverse renal outcomes [6]. There are several novel biomarkers including urinary angiostatin, vascular cell adhesion molecule 1, immunoglobulin binding protein 1, and the TNF-like weak inducer of apoptosis, which have been examined to reflect histological features of lupus nephritis and identify higher risk for renal outcome [7][8][9][10]. However, these biomarkers are still in its infancy and have not yet been widely used in clinical settings.…”