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:	Emilie Sundqvist, Dorothea Buck, Clemens Warnke, Eva Albrecht, Christian Gieger, Mohsen Khademi, Izaura Lima Bomfim, Anna Fogdell-Hahn, Jenny Link, Lars Alfredsson, Helle Bach Søndergaard, Jan Hillert, International Multiple Sclerosis Genetics Consortium, Annette B Oturai, Bernhard Hemmer, Ingrid Kockum, Tomas Olsson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9429a524df6b489ea87114c311c3e7c9
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spelling	oai:doaj.org-article:9429a524df6b489ea87114c311c3e7c92021-11-18T06:06:39ZJC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.1553-73661553-737410.1371/journal.ppat.1004084https://doaj.org/article/9429a524df6b489ea87114c311c3e7c92014-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24763718/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374JC 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-DRB115 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 DQB106:03 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-DR115 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB106:03 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.Emilie SundqvistDorothea BuckClemens WarnkeEva AlbrechtChristian GiegerMohsen KhademiIzaura Lima BomfimAnna Fogdell-HahnJenny LinkLars AlfredssonHelle Bach SøndergaardJan HillertInternational Multiple Sclerosis Genetics ConsortiumAnnette B OturaiBernhard HemmerIngrid KockumTomas OlssonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 4, p e1004084 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Emilie Sundqvist Dorothea Buck Clemens Warnke Eva Albrecht Christian Gieger Mohsen Khademi Izaura Lima Bomfim Anna Fogdell-Hahn Jenny Link Lars Alfredsson Helle Bach Søndergaard Jan Hillert International Multiple Sclerosis Genetics Consortium Annette B Oturai Bernhard Hemmer Ingrid Kockum Tomas Olsson JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.
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-DRB115 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 DQB106:03 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-DR115 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB106:03 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.
format	article
author	Emilie Sundqvist Dorothea Buck Clemens Warnke Eva Albrecht Christian Gieger Mohsen Khademi Izaura Lima Bomfim Anna Fogdell-Hahn Jenny Link Lars Alfredsson Helle Bach Søndergaard Jan Hillert International Multiple Sclerosis Genetics Consortium Annette B Oturai Bernhard Hemmer Ingrid Kockum Tomas Olsson
author_facet	Emilie Sundqvist Dorothea Buck Clemens Warnke Eva Albrecht Christian Gieger Mohsen Khademi Izaura Lima Bomfim Anna Fogdell-Hahn Jenny Link Lars Alfredsson Helle Bach Søndergaard Jan Hillert International Multiple Sclerosis Genetics Consortium Annette B Oturai Bernhard Hemmer Ingrid Kockum Tomas Olsson
author_sort	Emilie Sundqvist
title	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_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_sort	jc polyomavirus infection is strongly controlled by human leucocyte antigen class ii variants.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/9429a524df6b489ea87114c311c3e7c9
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JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.

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