The Diagnostic and Prognosis Potential of B Cell Repertoire in Membranous Nephropathy

Abstract

Background: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, which is an autoimmune glomerular disease. In current clinical practice, the diagnosis is dependent on renal tissue biopsy. A non-invasive method for diagnosis and prognosis surveillance is urgent need for patients. Methods: From 2017 to 2018 we recruited 66 MN patients before any treatment and 11 healthy controls. We analyzed multiple aspects of immunoglobulin heavy chain (IGH) repertoire between MN patients and healthy controls using high-throughput sequencing. Findings: We found that the frequency of IGHV3-66 in post-therapy patients is significantly lower than pre-therapy remarkably. Moreover, we found that IGHV3-38 gene is significantly related to PLA2R, which is the common used biomarker. The most important discovery was that in the patient before treatment we identified 24 IGHV genes had the potential to predict the therapeutic effect. Interpretation: Our study further demonstrates IGH repertoire can be a non-invasive biomarkers potentially for prognosis prediction of MN. The landscape of circulating B-lymphocyte repertoires shed new light on MN detection and surveillance. Funding Statement: This work was funded by grants from the National Natural Science Foundation of China (81972335) and Guangdong Provincial Science and Technology Plan (2017A020215185) and Guangdong Province Natural Science Funds for Distinguished Young Scholar (2016A030306050) and Science and Technology Innovation Platform in Foshan City (FS0AA-KJ218-1301-0007) and “Guangdong Te Zhi Program” youth science and technology talent project (2015TQ01R462) and Medical Scientific Research Foundation of Guangdong Province of China (B2017006). Declaration of Interests: The authors declare no financial or commercial conflicts of interest. Ethics Approval Statement: This study was approved by the ethics committee of the Affiliated Foshan Hospital of Sun Yat-Sen University.