AB0133 Blood concentration of immunoglobulin binding protein 1 as a biomarker to predict lupus nephritis

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.

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Plasma immunoglobulin binding protein 1 as a predictor of development of lupus nephritis

Lupus ◽

10.1177/0961203320912336 ◽

2020 ◽

Vol 29 (6) ◽

pp. 547-553

Author(s):

Oh Chan Kwon ◽

Eun-Ju Lee ◽

Ji Seon Oh ◽

Seokchan Hong ◽

Chang-Keun Lee ◽

...

Keyword(s):

Regression Analysis ◽

Lupus Nephritis ◽

Future Development ◽

Predictive Value ◽

Cox Regression ◽

Binding Protein ◽

Cox Regression Analysis ◽

Dsdna Antibody ◽

Immunoglobulin Binding Protein ◽

Immunoglobulin Binding

Objective Urine levels of immunoglobulin binding protein 1 (IGBP1) are increased in patients with lupus nephritis (LN) compared with systemic lupus erythematosus (SLE) patients without nephritis. However, the clinical significance of IGBP1 level in plasma is unclear. We aimed to evaluate whether the plasma level of IGBP1 can predict future development of LN in SLE patients without nephritis. Methods Forty-three SLE patients without nephritis were followed for 5 years. Plasma IGBP1 levels were measured using ELISA, and clinical and laboratory data were obtained at study entry. Development of LN was confirmed by renal biopsy. Cox regression analysis was performed to identify factors associated with development of LN, and receiver operating characteristic curve analysis was used to determine the predictive value of each factor. Results Of the total 43 patients, eight (18.6%) developed LN during the follow-up period. Compared with patients who did not develop LN, those who developed LN had higher levels of plasma IGBP1 (6.3 ng/ml (range 4.3–9.6 ng/mL) vs. 13.3 ng/ml (range 7.2–31.3 ng/ml); p = 0.023). In the Cox regression analysis, higher CRP (hazard ratio (HR) = 1.325, 95% confidence interval (CI) 1.073–1.637, p = 0.009), anti-dsDNA antibody (Ab; HR = 1.066, 95% CI 1.012–1.124, p = 0.017) and plasma IGBP1 (HR = 1.091, 95% CI 1.034–1.152, p = 0.002) were associated with future development of LN. Among these factors, anti-dsDNA Ab (area under the curve (AUC)=0.893) had the highest predictive value followed by plasma IGBP1 (AUC = 0.761) and CRP (AUC = 0.634). A combination of anti-dsDNA Ab and plasma IGBP1 as a composite predictor was highly specific (97%) for predicting the development of LN. Conclusions Plasma IGBP1 can be used complementarily with anti-dsDNA Ab for detecting SLE patients at a higher risk of developing LN.

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