Background Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease of unknown etiology, and renal involvement is an important factor associated with a high morbidity and mortality. Immunoglobulin binding protein 1 (IGBP1) is a phosphoprotein associated with Ig-α of the B cell receptor complex. Intracellular IGBP1 interacts with the catalytic subunit of protein phosphatase (PP2A) and regulates differentiation, proliferation, and apoptosis of B cells. Functional studies reported that high PP2A levels alter the phenotype and function of T cells in SLE patients. Recently, we reported that urinary IGBP1 levels were associated with the pathologic activity in lupus nephritis (LN). However, the role of plasma IGBP1 (pIGBP1) in the clinical features including the development of nephritis has not been identified in SLE.
Objectives To determine the role of pIGBP1 as a biomarker related with LN.
Methods Blood samples of SLE patients were collected between Jan 2009 and Dec 2010 in a tertiary hospital. The levels of pIGBP1 were measured in SLE patients with (n=44) or without (n=39) nephritis, and healthy subjects (n=14). Clinical parameters including baseline characteristics, laboratory data, medications and SLE Disease Activity Index (SLEDAI) were collected from electronic medical record. Activity and chronicity index in renal pathology of LN were scored blindly by a renal pathologist. To identify factors related to the development of LN, Cox proportional hazard regression model and Kaplan-Meier curves were used.
Results The concentrations of pIGBP1 in SLE patient were higher than those in healthy individual (9.6±8.4 ng/mL vs 4.5±2.4 ng/ml) and positively correlated with SLEDAI score. However, the concentrations were not different between LN and non-nephritis SLE and were not associated with activity index score in renal pathology. During follow-up more than 5 years, nephritis was developed in 8 patients (20.5%) among 39 SLE patients who did not have renal involvement at baseline. Interestingly, levels of pIGBP1 (p=0.002), CRP (p=0.009), or anti-dsDNA antibody (p=0.03) were significantly elevated in 8 patients who developed LN compared to who did not. Kaplan-Meier survival curve showed that initial pIGBP1 (>10.71 ng/mL) as well as anti-dsDNA (>30.7 IU/mL) were associated with high probability of LN development in the future.
Conclusions Based on our results, high concentration of pIGBP1 could be a valuable marker to represent high SLE activity and a predictor for developing nephritis in SLE patients.
Lee EJ, Hong S, Lim DH, et al. Increased levels of immunoglobulin binding protein 1 are associated with disease activity including renal damage in patients with systemic lupus erythematosus. Presented in 2015 ACR/ARHP Annual meeting.
Sunahori K, Nagpal K, Hedrich CM, et al. The catalytic subunit of protein phosphatase 2A (PP2Ac) promotes DNA hypomethylation by suppressing the phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/phosphorylated ERK/DNMT1 protein pathway in T-cells from controls and systemic lupus erythematosus patients. J Biol Chem. 2013, 288(30):21936–44.
Acknowledgements This work was supported by the National Research Foundation of Korea (NRF-2016R1A6A3A11930269).
Disclosure of Interest None declared