Early childhood CMV infection may decelerate the progression to clinical type 1 diabetes

Pediatr Diabetes. 2019 Feb;20(1):73-77. doi: 10.1111/pedi.12788. Epub 2018 Nov 19.

Abstract

Aims/hypothesis: Evidence of the role of cytomegalovirus (CMV) infection in the pathogenesis of type 1 diabetes (T1D) has remained inconclusive. Our aim was to elucidate the possible role of CMV infection in the initiation of islet autoimmunity and in the progression to clinical T1D among children with human leukocyte antigen (HLA)-conferred T1D risk.

Methods: A total of 1402 children from the prospective Type 1 Diabetes Prediction and Prevention (DIPP) study were analyzed for CMV-specific IgG antibodies during early childhood. All the children carried HLA-DQ genotypes associated with increased risk for T1D. The effect of CMV infection on the appearance of T1D-associated autoantibodies (insulin autoantibodies [IAA], glutamic acid decarboxylase [GADA], and insulinoma antigen-2 [IA-2A], n = 356) and on the progression rate to clinical T1D (n = 233) were analyzed with Kaplan-Meier survival analysis and Log-rank test.

Results: Early childhood CMV infection was inversely associated with the development of T1D during childhood. Cumulative progression to T1D was decreased in subjects with an early CMV infection (P = 0.035). In further analyses, the effect of early CMV infection on the initiation of islet autoimmunity and progression to clinical T1D were examined separately. Interestingly, early CMV infection did not affect the appearance of T1D-associated autoantibodies but a decelerating effect was observed on the progression rate from islet autoimmunity to clinical T1D (P = 0.015).

Conclusion: Our results suggest that an early childhood CMV infection may decelerate the progression from islet autoimmunity to clinical T1D among at-risk children and may thus protect these children from progressing to T1D during childhood.

Keywords: CMV; autoantibodies; cytomegalovirus; type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Autoantibodies / blood
  • Autoimmunity / physiology
  • Child
  • Child, Preschool
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / epidemiology*
  • Cytomegalovirus Infections / immunology
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology*
  • Disease Progression
  • Female
  • Finland / epidemiology
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • HLA-DQ Antigens / genetics
  • Humans
  • Infant
  • Islets of Langerhans / immunology
  • Male
  • Risk Factors

Substances

  • Autoantibodies
  • HLA-DQ Antigens