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JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants
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نویسنده
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sundqvist e. ,buck d. ,warnke c. ,albrecht e. ,gieger c. ,khademi m. ,lima bomfim i. ,fogdell-hahn a. ,link j. ,alfredsson l. ,søndergaard h.b. ,hillert j. ,barcellos l. ,booth d. ,mccauley j.l. ,comabella m. ,compston a. ,dalfonso s. ,de jager p. ,fontaine b. ,goris a. ,hafler d. ,haines j. ,harbo h.f. ,hauser s.l. ,hawkins c. ,hemmer b. ,hillert j. ,ivinson a. ,kockum i. ,martin r. ,boneschi f.m. ,oksenberg j. ,olsson t. ,oturai a. ,patsopoulos n. ,pericak-vance m. ,saarela j. ,sawcer s. ,spurkland a. ,stewart g. ,zipp f. ,oturai a.b. ,hemme b. ,kockum i. ,olsson t.
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منبع
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plos pathogens - 2014 - دوره : 10 - شماره : 4
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چکیده
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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. © 2014 sundqvist et al.
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آدرس
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neuroimmunology unit,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, department of neurology,technische universität münchen,munich, Germany, the multiple sclerosis research group,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, institute of genetic epidemiology,helmholtz zentrum münchen - german research center for environmental health,neuherberg, Germany, institute of genetic epidemiology,helmholtz zentrum münchen - german research center for environmental health,neuherberg, Germany, neuroimmunology unit,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, neuroimmunology unit,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, the multiple sclerosis research group,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, the multiple sclerosis research group,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, institute for environmental medicine,karolinska institutet,stockholm, Sweden, danish multiple sclerosis center,department of neurology,copenhagen university hospital,rigshospitalet,copenhagen, Denmark, the multiple sclerosis research group,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, genetic epidemiology and genomics laboratory,division of epidemiology,school of public health,university of california,berkeley,ca, United States, westmead millennium institute,university of sydney,new south wales 2145, Australia, john p. hussman institute for human genomics,the dr. john t macdonald foundation department of human genetics,university of miami,miller school of medicine,miami,fl, United States, clinical neuroinmunology unit,multiple sclerosis center of catalonia (cem-cat),vall d'hebron university hospital,barcelona, Spain, department of clinical neurosciences,university of cambridge,addenbrooke's hospital,cambridge,cb2 0qq, United Kingdom, department of medical sciences and interdisciplinary research center of autoimmune diseases (ircad),university of eastern,piedmont,novara, Italy, department of neurology,brigham and women's hospital and harvard medical school,boston,ms, United States, laboratory for neuroimmunology,section for experimental neurology,katholieke universiteit leuven,leuven, Belgium, inserm umr s 975 cricm,upmc,département de neurologie pitié-salpêtrière,ap-hp,75013 paris, France, departments of neurology and immunobiology,yale school of medicine,new haven,ct, United States, center for human genetics research,vanderbilt university medical center,519 light hall,nashville,tn 37232, United States, department of neurology,oslo university hospital,ullevål and university of oslo,oslo, Norway, department of neurology,university of california san francisco,san francisco, United States, keele university medical school,stoke-on-trent st4 7ny, United Kingdom, klinik fur neurologie,klinikum rechts der isar,technische universitat,munchen, Germany, ms research group,department of clinical neuroscience,centre for molecular medicine. karolinska institutet,karolinska university hospital,stockholm, Sweden, harvard neuro discovery center,harvard medical school,boston,ma, United States, neuroimmunology unit,center for molecular medicine,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, department of neurology,university hospital zurich,university zurich, Switzerland, department of neurology,institute of experimental neurology (inspe),division of neuroscience,san raffaele scientific institute,milan, Italy, department of neurology,university of california san francisco,san francisco, United States, neuroimmunology unit,center for molecular medicine,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, danish multiple sclerosis center,university of copenhagen and department of neurology,rigshospitalet,copenhagen, Denmark, department of neurology,brigham and women's hospital and harvard medical school,boston,ms, United States, john p. hussman institute for human genomics,the dr. john t macdonald foundation department of human genetics,university of miami,miller school of medicine,miami,fl, United States, institute for molecular medicine finland fimm,university of helsinki,helsinki, Finland, department of clinical neurosciences,university of cambridge,addenbrooke's hospital,cambridge,cb2 0qq, United Kingdom, institute of basal medical sciences,university of oslo, Norway, westmead millennium institute,university of sydney,new south wales 2145, Australia, department of neurology,university medicine mainz,johannes gutenberg university mainz,mainz, Germany, danish multiple sclerosis center,department of neurology,copenhagen university hospital,rigshospitalet,copenhagen, Denmark, department of neurology,technische universität münchen,munich,germany,munich cluster for systems neurology (synergy),munich, Germany, neuroimmunology unit,department of clinical neuroscience,karolinska institutet,stockholm, Sweden, neuroimmunology unit,department of clinical neuroscience,karolinska institutet,stockholm, Sweden
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Authors
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