title: Enterovirus infection may induce humoral immune response reacting with islet cell autoantigens in humans.
abstract: Molecular mimicry is one of the mechanisms by which enterovirus infections have been postulated to have a role in the pathogenesis of type 1 diabetes. Immunogenic epitopes in enterovirus capsid protein VP1 and procapsid protein VP0 have sequence similarities with diabetes-associated epitopes in tyrosine phosphatase IA-2/IAR and heat shock protein 60. In the present study, documented enterovirus infection was shown to induce humoral responses, that in 7% and 1% of patients cross-reacted with the known diabetes-associated epitopes in tyrosine phosphatase IAR and heat shock protein 60, respectively. In contrast, none of the children vaccinated against poliomyelitis had antibodies to the diabetes-associated epitope of tyrosine phosphatases IA-2/IAR. The antibody response studied in serum samples from six patients with coxsackievirus A9 infection was mainly targeted to capsid protein VP1. Coxsackievirus A9 infection induced antibodies cross-reacted with one epitope in heat shock protein 60, but not with epitopes derived from other autoantigens. Most diabetic children had high levels of antibodies to both coxsackievirus and poliovirus derived VP1 peptides but the pattern of reactivity did not differ from that seen in healthy children. The reactivity of linear epitopes derived from autoantigens was low in general and associated with the presence of multiple autoantibodies in the patients. Some linear auto-epitopes derived from tyrosine phosphatase IA-2, glutamic acid decarboxylase 65, preproinsulin, and heat shock protein 60 were recognized by sera from diabetic patients, but not by sera from healthy children. In conclusion, enteroviruses may induce immune responses that react with islet cell autoantigens, which is a concern when a putative inactivated enterovirus vaccine is considered.
authors.affiliation: Enterovirus Laboratory, National Public Health Institute (KTL), Helsinki, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.forename: Anja
authors.initials: A
authors.lastname: Paananen
authors.forename: Hilkka
authors.initials: H
authors.lastname: Lankinen
authors.forename: Tapani
authors.initials: T
authors.lastname: Hovi
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: Merja
authors.initials: M
authors.lastname: Roivainen
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology*; D018834:Chaperonin 60 / Q000737:chemistry / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D029822:Enterovirus B, Human / Q000276:immunology; D004769:Enterovirus Infections / Q000276:immunology* / Q000821:virology; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000276:immunology*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D001324:Autoantigens; D036022:Capsid Proteins; D018834:Chaperonin 60; D008565:Membrane Proteins; D010455:Peptides; D011054:Poliovirus Vaccine, Inactivated; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8