title: Detection of enterovirus RNA in peripheral blood mononuclear cells of type 1 diabetic patients beyond the stage of acute infection.
abstract: Previous studies have shown that enteroviral RNA can be detected in blood at the onset of type 1 diabetes (T1D). The infection may play a role in triggering T1D and genetic host factors may contribute to this process. We investigated (1) whether enterovirus is present at the onset of T1D in peripheral blood mononuclear cells (PBMC), plasma, throat, or stool, and (2) whether enteroviral presence is linked with HLA-DR type and/or polymorphisms in melanoma differentiation-associated gene 5 (MDA5) and 2'-5' oligoadenylate synthetase 1 (OAS1), factors of antiviral immunity. To this end, PBMC, plasma, throat, and stool samples from 10 T1D patients and 20 unrelated controls were tested for the presence of enteroviruses (RT-PCR), for HLA-DR type, and polymorphisms in MDA5 and OAS1. Enterovirus RNA was detected in PBMC of 4/10 T1D patients, but none of 20 controls. Plasma was positive in 2/10 T1D patients and none of 20 controls, suggesting that enteroviruses found at the onset of T1D are mainly present in PBMC. All throat samples from positive T1D patients were virus-negative and only 1 fecal sample was positive. The negative results for all throat and most stool samples argues against acute infection. Enterovirus presence was linked with HLA-DR4, but not with polymorphisms in MDA5 or OAS1.
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands. b.schulte@ncmls.ru.nl
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Schulte
authors.forename: Judith
authors.initials: J
authors.lastname: Bakkers
authors.forename: Kjerstin H W
authors.initials: KH
authors.lastname: Lanke
authors.forename: Willem J G
authors.initials: WJ
authors.lastname: Melchers
authors.forename: Ciska
authors.initials: C
authors.lastname: Westerlaken
authors.forename: Wil
authors.initials: W
authors.lastname: Allebes
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Aanstoot
authors.forename: G Jan
authors.initials: GJ
authors.lastname: Bruining
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: Van Kuppeveld
authors.forename: Jochem M D
authors.initials: JM
authors.lastname: Galama
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000293:Adolescent; D001769:Blood / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D053487:DEAD-box RNA Helicases / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000821:virology*; D004770:Enterovirus / Q000235:genetics / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000150:complications* / Q000821:virology*; D005243:Feces / Q000821:virology; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D010614:Pharynx / Q000821:virology; D010949:Plasma / Q000821:virology; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D006684:HLA-DR Antigens; D012367:RNA, Viral; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1