title: Coxsackievirus B1 is associated with induction of β-cell autoimmunity that portends type 1 diabetes.
abstract: The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study. The study participants comprised 183 case children testing persistently positive for at least two diabetes-predictive autoantibodies and 366 autoantibody-negative matched control children. Coxsackievirus B1 was associated with an increased risk of β-cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and was attenuated by the presence of maternal antibodies against the virus. Two other coxsackieviruses, B3 and B6, were associated with a reduced risk, with an interaction pattern, suggesting immunological cross-protection against coxsackievirus B1. These results support previous observations suggesting that the group B coxsackieviruses are associated with the risk of type 1 diabetes. The clustering of the risk and protective viruses to this narrow phylogenetic lineage supports the biological plausibility of this phenomenon.
authors: Vactech Ltd., Tampere, Finland.
authors: Olli H
authors: OH
authors: Laitinen
authors: Hanna
authors: H
authors: Honkanen
authors: Outi
authors: O
authors: Pakkanen
authors: Sami
authors: S
authors: Oikarinen
authors: Minna M
authors: MM
authors: Hankaniemi
authors: Heini
authors: H
authors: Huhtala
authors: Tanja
authors: T
authors: Ruokoranta
authors: Valérie
authors: V
authors: Lecouturier
authors: Philippe
authors: P
authors: André
authors: Raimo
authors: R
authors: Harju
authors: Suvi M
authors: SM
authors: Virtanen
authors: Jussi
authors: J
authors: Lehtonen
authors: Jeffrey W
authors: JW
authors: Almond
authors: Tuula
authors: T
authors: Simell
authors: Olli
authors: O
authors: Simell
authors: Jorma
authors: J
authors: Ilonen
authors: Riitta
authors: R
authors: Veijola
authors: Mikael
authors: M
authors: Knip
authors: Heikki
authors: H
authors: Hyöty
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology* / Q000821:virology; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology*; D004769:Enterovirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology*; D005786:Gene Expression Regulation / Q000502:physiology; D005838:Genotype; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology*; D010802:Phylogeny; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen