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The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis

Primary focal segmental glomerulosclerosis (FSGS), typically characterized by diffuse podocyte foot process effacement and nephrotic syndrome (diffuse podocytopathy), is generally attributed to a circulating permeability factor. Primary FSGS can recur after transplantation where it manifests as diff...

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Autores principales: Batal, Ibrahim, Khairallah, Pascale, Weins, Astrid, Andeen, Nicole K., Stokes, Michael B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995699/
https://www.ncbi.nlm.nih.gov/pubmed/36911713
http://dx.doi.org/10.3389/fimmu.2023.1124249
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author Batal, Ibrahim
Khairallah, Pascale
Weins, Astrid
Andeen, Nicole K.
Stokes, Michael B.
author_facet Batal, Ibrahim
Khairallah, Pascale
Weins, Astrid
Andeen, Nicole K.
Stokes, Michael B.
author_sort Batal, Ibrahim
collection PubMed
description Primary focal segmental glomerulosclerosis (FSGS), typically characterized by diffuse podocyte foot process effacement and nephrotic syndrome (diffuse podocytopathy), is generally attributed to a circulating permeability factor. Primary FSGS can recur after transplantation where it manifests as diffuse foot process effacement in the early stages, with subsequent evolution of segmental sclerotic lesions. Previous published literature has been limited by the lack of stringent selection criteria to define primary FSGS. Although immunogenetic factors play an important role in many glomerular diseases, their role in recurrent primary FSGS post-transplantation has not been systematically investigated. To address this, we retrospectively studied a multicenter cohort of 74 kidney allograft recipients with end stage kidney disease due to primary FSGS, confirmed by clinical and histologic parameters. After adjusting for race/ethnicity, there was a numeric higher frequency of HLA-A30 antigen in primary FSGS (19%) compared to each of 22,490 healthy controls (7%, adjusted OR=2.0, P=0.04) and 296 deceased kidney donors (10%, OR=2.1, P=0.03). Within the group of transplant patients with end stage kidney disease due to primary FSGS, donor HLA-A30 was associated with recurrent disease (OR=9.1, P=0.02). Multivariable time-to-event analyses revealed that recipients who self-identified as Black people had lower risk of recurrent disease, probably reflecting enrichment of these recipients with APOL1 high-risk genotypes. These findings suggest a role for recipient and donor immunogenetic makeup in recurrent primary FSGS post-transplantation. Further larger studies in well-defined cohorts of primary FSGS that include high-resolution HLA typing and genome-wide association are necessary to refine these hereditary signals.
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spelling pubmed-99956992023-03-10 The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis Batal, Ibrahim Khairallah, Pascale Weins, Astrid Andeen, Nicole K. Stokes, Michael B. Front Immunol Immunology Primary focal segmental glomerulosclerosis (FSGS), typically characterized by diffuse podocyte foot process effacement and nephrotic syndrome (diffuse podocytopathy), is generally attributed to a circulating permeability factor. Primary FSGS can recur after transplantation where it manifests as diffuse foot process effacement in the early stages, with subsequent evolution of segmental sclerotic lesions. Previous published literature has been limited by the lack of stringent selection criteria to define primary FSGS. Although immunogenetic factors play an important role in many glomerular diseases, their role in recurrent primary FSGS post-transplantation has not been systematically investigated. To address this, we retrospectively studied a multicenter cohort of 74 kidney allograft recipients with end stage kidney disease due to primary FSGS, confirmed by clinical and histologic parameters. After adjusting for race/ethnicity, there was a numeric higher frequency of HLA-A30 antigen in primary FSGS (19%) compared to each of 22,490 healthy controls (7%, adjusted OR=2.0, P=0.04) and 296 deceased kidney donors (10%, OR=2.1, P=0.03). Within the group of transplant patients with end stage kidney disease due to primary FSGS, donor HLA-A30 was associated with recurrent disease (OR=9.1, P=0.02). Multivariable time-to-event analyses revealed that recipients who self-identified as Black people had lower risk of recurrent disease, probably reflecting enrichment of these recipients with APOL1 high-risk genotypes. These findings suggest a role for recipient and donor immunogenetic makeup in recurrent primary FSGS post-transplantation. Further larger studies in well-defined cohorts of primary FSGS that include high-resolution HLA typing and genome-wide association are necessary to refine these hereditary signals. Frontiers Media S.A. 2023-02-23 /pmc/articles/PMC9995699/ /pubmed/36911713 http://dx.doi.org/10.3389/fimmu.2023.1124249 Text en Copyright © 2023 Batal, Khairallah, Weins, Andeen and Stokes https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Batal, Ibrahim
Khairallah, Pascale
Weins, Astrid
Andeen, Nicole K.
Stokes, Michael B.
The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis
title The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis
title_full The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis
title_fullStr The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis
title_full_unstemmed The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis
title_short The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis
title_sort role of hla antigens in recurrent primary focal segmental glomerulosclerosis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995699/
https://www.ncbi.nlm.nih.gov/pubmed/36911713
http://dx.doi.org/10.3389/fimmu.2023.1124249
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