Incomplete Immune Response to Coxsackie B Viruses Associates With Early Autoimmunity Against Insulin

Sci Rep. 2016 Sep 8;6:32899. doi: 10.1038/srep32899.

Abstract

Viral infections are associated with autoimmunity in type 1 diabetes. Here, we asked whether this association could be explained by variations in host immune response to a putative type 1 etiological factor, namely coxsackie B viruses (CVB). Heterogeneous antibody responses were observed against CVB capsid proteins. Heterogeneity was largely defined by different binding to VP1 or VP2. Antibody responses that were anti-VP2 competent but anti-VP1 deficient were unable to neutralize CVB, and were characteristic of children who developed early insulin-targeting autoimmunity, suggesting an impaired ability to clear CVB in early childhood. In contrast, children who developed a GAD-targeting autoimmunity had robust VP1 and VP2 antibody responses to CVB. We further found that 20% of memory CD4(+) T cells responding to the GAD65247-266 peptide share identical T cell receptors to T cells responding to the CVB4 p2C30-51 peptide, thereby providing direct evidence for the potential of molecular mimicry as a mechanism for GAD autoimmunity. Here, we highlight functional immune response differences between children who develop insulin-targeting and GAD-targeting autoimmunity, and suggest that children who lose B cell tolerance to insulin within the first years of life have a paradoxical impaired ability to mount humoral immune responses to coxsackie viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies / immunology
  • Autoimmunity*
  • CD4-Positive T-Lymphocytes / metabolism
  • Capsid Proteins / immunology
  • Child
  • Child, Preschool
  • Coxsackievirus Infections / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / virology*
  • Enterovirus B, Human / immunology*
  • Female
  • Glutamate Decarboxylase / immunology
  • Glutamate Decarboxylase / metabolism
  • Humans
  • Insulin / immunology*
  • Male

Substances

  • Antibodies
  • Capsid Proteins
  • Insulin
  • Glutamate Decarboxylase