Plasma CXCL16 May Predict Renal Inflammation and the Progression of Immunoglobulin a Nephropathy

Abstract

Background. A recognized non-invasive biomarker to improve risk stratification of IgA nephropathy (IgAN) patients is scarce. CXCL16 has been shown to play a key role in inflammatory disease as chemoattractant, adhesion and even fibrosis factor. The current study assessed possibility of plasma CXCL16 as a novel biomarker in IgAN patient. Methods. Plasma CXCL16 was measured in 230 patients with renal biopsy consistent IgAN from 2012 to 2014, and clinical, pathological and prognostic relationships were analyzed. Results. The plasma CXCL16 levels in IgAN patients were significantly correlated with the uric acid and estimated glomerular filtration rate by both univariate and multivariate analysis. Tubular atrophy/interstitial fibrosis score was still significantly correlated with the plasma CXL16 levels even after adjustment for other potential predictor variables by multivariate analysis. In addition, the counts of CD4+ T cells, CD8+ T cells and CD20+ B cells in renal biopsies of IgAN patients were significantly correlated with the plasma CXCL16 levels, but not CD68+ macrophage. Finally, we concluded that patients with higher plasma CXCL16 levels had higher risk of poor renal outcome compared with those with lower plasma CXCL16 levels. No association was observed between the CXCL16 polymorphisms and clinical parameters including plasma CXCL16 levels and prognosis. Human kidney cells (HK2) expression of CXCL16 was up-regulated by interferon-γ (IFN-γ) via p65 pathway and recombinant CXCL16 promoted the chemotaxis of Jurkat T cells. Conclusions: Plasma CXCL16 levels were associated with creatinine level, 24-urine protein, tubular atrophy/interstitial fibrosis pathological damage, the CD4+ T cells, CD8+ T cells and CD20+ B cells infiltration in renal tissue and renal outcome in IgAN patients. Plasma CXCL16 might be a potential prognosis novel predictor in Chinese patients with IgAN. Funding: This work was financially supported by the Major Research Plan of the National Natural Science Foundation of China (Grant No. 91742204); International (regional) cooperation and exchange projects, (NSFC-DFG, Grant No. 81761138041), National Natural Science Foundation of China (Grants 81470948, 81670633, 81570667), National key research and development program (Grants 2016YFC0906103) and The National Key Technology R&D Program (Grant 2013BAI09B06, 2015BAI12B07). Declaration of Interest: We declare no competing interests. Ethical Approval: This study conformed with the Declaration of Helsinki and approved by the Huazhong University of Science and Technology, Tongji Hospital Ethics Committee on Human Experimentation. Written informed consent was obtained from each patient.