Serum IGFBP2, IGFBP4, and sTNFR2 are predictive of concurrent clinical and histological nephritis in SLE

Abstract

Abstract Background Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that targets various body systems, including the kidneys, leading to Lupus Nephritis (LN). Present diagnostic methods for LN include the renal biopsy, which is invasive. This project takes advantage of a large cohort of LN samples where the serum samples were obtained at the time of renal biopsy. Our goal is to identify serum protein markers that are predictive of concurrent clinical and histological nephritis. Methods Serum samples from 10 healthy controls and 66 SLE patients with active renal disease obtained at the time of renal biopsy were ELISA-tested for levels of IGFBP2, IGFBP4, and sTNFR2, selected because they were elevated in LN patients in previous screening studies. Results Serum sTNRF2 (p < 0.0001), IGFBP2 (p < 0.0001) and IGFBP4 (p < 0.05) were all elevated in LN patients compared to healthy controls. Concurrently measured Glomerular Filtration Rate was negatively correlated with serum IGFBP4 (p < 0.0001), IGFBP2 (p < 0.05) and sTNFR2 (p < 0.001). Serum IGFBP4 correlated with SLEDAI (p < 0.01), and Renal SLEDAI (p < 0.01). All 3 serum proteins showed a positive correlation with Renal SLICC scores with IGFBP4 being the strongest (p < 0.0001). There was also a significant correlation between various concurrent renal biopsy pathology lesions with the assayed serum proteins, notably IGFBP4 (p < 0.0001). Conclusion Serum IGFBP2, IGFBP4, and sTNFR2 are predictive of concurrent clinical nephritis activity in LN as well as histological changes on renal biopsy. Whereas the biopsy is subject to sampling errors, the assayed proteins may represent more stable biomarkers of renal pathology changes in LN.