JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants
Articolo
Data di Pubblicazione:
2014
Citazione:
JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants / E. Sundqvist, D. Buck, C. Warnke, E. Albrecht, C. Gieger, M. Khademi, I. Lima Bomfim, A. Fogdell-Hahn, J. Link, L. Alfredsson, H.B. Søndergaard, J. Hillert, L. Barcellos, D. Booth, J.L. Mccauley, M. Comabella, A. Compston, S. Dalfonso, P. De Jager, B. Fontaine, A. Goris, D. Hafler, J. Haines, H.F. Harbo, S.L. Hauser, C. Hawkins, B. Hemmer, J. Hillert, A. Ivinson, I. Kockum, R. Martin, F. MARTINELLI BONESCHI, J. Oksenberg, T. Olsson, A. Oturai, N. Patsopoulos, M. Pericak-Vance, J. Saarela, S. Sawcer, A. Spurkland, G. Stewart, F. Zipp, A.B. Oturai, B. Hemme, I. Kockum, T. Olsson. - In: PLOS PATHOGENS. - ISSN 1553-7366. - 10:4(2014), pp. e1004084.1-e1004084.11. [10.1371/journal.ppat.1004084]
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
CD4-Positive T-Lymphocytes; Female; HLA-DQ beta-Chains; HLA-DRB1 Chains; Humans; Male; Polyomavirus Infections; Scandinavian and Nordic Countries; Alleles; Haplotypes; JC Virus; Parasitology; Microbiology; Immunology; Molecular Biology; Genetics; Virology
Elenco autori:
E. Sundqvist, D. Buck, C. Warnke, E. Albrecht, C. Gieger, M. Khademi, I. Lima Bomfim, A. Fogdell-Hahn, J. Link, L. Alfredsson, H.B. Søndergaard, J. Hillert, L. Barcellos, D. Booth, J.L. Mccauley, M. Comabella, A. Compston, S. Dalfonso, P. De Jager, B. Fontaine, A. Goris, D. Hafler, J. Haines, H.F. Harbo, S.L. Hauser, C. Hawkins, B. Hemmer, J. Hillert, A. Ivinson, I. Kockum, R. Martin, F. MARTINELLI BONESCHI, J. Oksenberg, T. Olsson, A. Oturai, N. Patsopoulos, M. Pericak-Vance, J. Saarela, S. Sawcer, A. Spurkland, G. Stewart, F. Zipp, A.B. Oturai, B. Hemme, I. Kockum, T. Olsson
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