Study to clarify the pathophysiology of childhood nephrotic syndrome and HLA class II

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16892
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kobe University
• Principal Investigator: Horinouchi Tomoko 神戸大学, 医学研究科, 助教 (30754593)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 小児ネフローゼ症候群 / ステロイド感受性ネフローゼ症候群 / 自己抗体 / HLA class II / ネフリン / NPHS1

Outline of Final Research Achievements

Many patients with childhood idiopathic nephrotic syndrome are steroid-sensitive (SSNS). Several genome-wide association studies have shown that HLA class II, which is related to immunity, and NPHS1, which encodes nephrin in glomeruli, are involved in pediatric SSNS. HLA class II genes are associated with susceptibility to many kinds of autoimmune diseases, one of the mechanisms being misfolded protein/HLA class II complexes, which is aberrantly transported to the cell surface in the affected tissues inducing immune responses. In this study, we investigated the relationship between each HLA allele and nephrin based on the hypothesis that nephrin protein/HLA class II complexes might be involved in the development of SSNS. We also searched for autoantibodies that respond to the nephrin complex (neo-self).

Free Research Field

小児腎臓病学

Academic Significance and Societal Importance of the Research Achievements

小児ネフローゼ症候群において、日本人や欧米人において報告されているHLA class IIのRisk alleleによりコードされるHLA-DR分子はProtective alleleによりコードされるHLA-DR分子に比較し、ネフリンを抗原として呈示しやすい傾向があることが明らかになった。また、ネフリンやHLA class IIの複合体に対する自己抗体が存在する可能性が明らかになった。