Study to clarify the pathophysiology of childhood nephrotic syndrome and HLA class II
| 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 |
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| 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 / 小児特発性ネフローゼ症候群 / HLA |
|---|
| Outline of Research at the Start |
小児特発性ネフローゼ症候群（INS）は、最も発症頻度の高い小児慢性腎疾患であり、病態解明とそれに基づいた根本療法の開発が急務である。申請者らは小児SSNSを対象としたゲノムワイド関連解析(GWAS)においてHLA class II risk/protective alleleの存在と、腎糸球体スリット膜の重要構成因子であるネフリンをコードするNPHS1が疾患感受性遺伝子であることを明らかとした。本研究では、HLA class II alleleがネフリンを提示する細胞・マウスの各実験系を用いて小児SSNSの病態を解明し、根本治療開発の足掛かりとする。
|
| 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).
|
| 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。
|
Report
(4 results)
Research Products
(15 results)
-
-
-
[Journal Article] Cite Share Detecting MUC1 Variants in Patients Clinicopathologically Diagnosed With Having Autosomal Dominant Tubulointerstitial Kidney Disease2022
Author(s)
Okada E, Morisada N, Horinouchi T, Fujii H, Tsuji T, Miura M, Katori H, Kitagawa M, Morozumi K, Toriyama T, Nakamura Y, Nishikomori R, Nagai S, Kondo A, Aoto Y, Ishiko S, Rossanti R, Sakakibara N, Nagano C, Yamamura T, Ishimori S, Usui J, Yamagata K, Iijima K, Imasawa T, Nozu K.
-
Journal Title
Kidney Int Rep.
Volume: 7
Issue: 4
Pages: 857-866
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Presentation] 15.Treatment with antisense-oligonucleotide or splicing regulating proteins for X-linked Alport syndrome cases with deep intronic variants2021
Author(s)
Horinouchi Tomoko, Yamamura Tomohiko, Nagai Sadayuki, Kondo Atsushi, Aoto Yuya, Okada Eri, Rossanti Rini, Sakakibara Nana, Nagano China, Ninchoji Takeshi, Iijima Kazumoto, Nozu Kandai
Organizer
第64回日本腎臓学会学術総会
Related Report
-
-
-
-
[Presentation] Novel nephrin protein/HLA class II complexes: A new mechanism of steroid sensitive nephrotic syndrome2020
Author(s)
Tomoko Horinouchi, Sadayuki Nagai, Atsushi Kondo, Yuya Aoto, Shinya Ishiko, Rini Rossanti, Nana Sakakibara, China Nagano, Tomohiko Yamamura, Takeshi Ninchoji, Kandai Nozu, Kazumoto Iijima
Organizer
American Society of Nephrology, Kidney week 2020
Related Report
Int'l Joint Research
-
-
-
