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JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV ma...

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Autores principales: Sundqvist, Emilie, Buck, Dorothea, Warnke, Clemens, Albrecht, Eva, Gieger, Christian, Khademi, Mohsen, Lima Bomfim, Izaura, Fogdell-Hahn, Anna, Link, Jenny, Alfredsson, Lars, Søndergaard, Helle Bach, Hillert, Jan, Oturai, Annette B., Hemme, Bernhard, Kockum, Ingrid, Olsson, Tomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999271/
https://www.ncbi.nlm.nih.gov/pubmed/24763718
http://dx.doi.org/10.1371/journal.ppat.1004084
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author Sundqvist, Emilie
Buck, Dorothea
Warnke, Clemens
Albrecht, Eva
Gieger, Christian
Khademi, Mohsen
Lima Bomfim, Izaura
Fogdell-Hahn, Anna
Link, Jenny
Alfredsson, Lars
Søndergaard, Helle Bach
Hillert, Jan
Oturai, Annette B.
Hemme, Bernhard
Kockum, Ingrid
Olsson, Tomas
author_facet Sundqvist, Emilie
Buck, Dorothea
Warnke, Clemens
Albrecht, Eva
Gieger, Christian
Khademi, Mohsen
Lima Bomfim, Izaura
Fogdell-Hahn, Anna
Link, Jenny
Alfredsson, Lars
Søndergaard, Helle Bach
Hillert, Jan
Oturai, Annette B.
Hemme, Bernhard
Kockum, Ingrid
Olsson, Tomas
author_sort Sundqvist, Emilie
collection PubMed
description JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50–60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(−15)) and controls (OR = 0.53, p = 2×10(−5)). In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006), and controls (OR = 2.69, p = 1×10(−5)). The German dataset confirmed these findings (OR = 0.54, p = 1×10(−4) and OR = 1.58, p = 0.03 respectively for these haplotypes). HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and lays the ground for risk stratification for PML and development of therapy and prevention.
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spelling pubmed-39992712014-04-29 JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants Sundqvist, Emilie Buck, Dorothea Warnke, Clemens Albrecht, Eva Gieger, Christian Khademi, Mohsen Lima Bomfim, Izaura Fogdell-Hahn, Anna Link, Jenny Alfredsson, Lars Søndergaard, Helle Bach Hillert, Jan Oturai, Annette B. Hemme, Bernhard Kockum, Ingrid Olsson, Tomas PLoS Pathog Research Article JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50–60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(−15)) and controls (OR = 0.53, p = 2×10(−5)). In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006), and controls (OR = 2.69, p = 1×10(−5)). The German dataset confirmed these findings (OR = 0.54, p = 1×10(−4) and OR = 1.58, p = 0.03 respectively for these haplotypes). HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and lays the ground for risk stratification for PML and development of therapy and prevention. Public Library of Science 2014-04-24 /pmc/articles/PMC3999271/ /pubmed/24763718 http://dx.doi.org/10.1371/journal.ppat.1004084 Text en © 2014 Sundqvist et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sundqvist, Emilie
Buck, Dorothea
Warnke, Clemens
Albrecht, Eva
Gieger, Christian
Khademi, Mohsen
Lima Bomfim, Izaura
Fogdell-Hahn, Anna
Link, Jenny
Alfredsson, Lars
Søndergaard, Helle Bach
Hillert, Jan
Oturai, Annette B.
Hemme, Bernhard
Kockum, Ingrid
Olsson, Tomas
JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants
title JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants
title_full JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants
title_fullStr JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants
title_full_unstemmed JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants
title_short JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants
title_sort jc polyomavirus infection is strongly controlled by human leucocyte antigen class ii variants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999271/
https://www.ncbi.nlm.nih.gov/pubmed/24763718
http://dx.doi.org/10.1371/journal.ppat.1004084
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