Novel minor HLA DR associated antigens in type 1 diabetes

Clin Immunol. 2018 Sep;194:87-91. doi: 10.1016/j.clim.2018.07.001. Epub 2018 Jul 7.


Type 1 diabetes is an autoimmune disease leading to insulin deficiency. Autoantibodies to beta cell proteins are already present in the asymptomatic phase of type 1 diabetes. Recent findings have suggested a number of additional minor autoantigens in patients with type 1 diabetes. We have established luciferase immunoprecipitation systems (LIPS) for anti-MTIF3, anti-PPIL2, anti-NUP50 and anti-MLH1 and analyzed samples from 500 patients with type 1 diabetes at onset of clinical disease and 200 healthy individuals who had a family history of type 1 diabetes but no evidence of beta cell autoantibodies. We show significantly higher frequencies of anti-MTIF3, anti-PPIL2 and anti-MLH1 in recent onset type 1 diabetes patients in comparison to controls. In addition, antibodies to NUP50 were associated with HLA-DRB1*03 and antibodies to MLH1 were associated with HLA-DRB1*04 genotypes.

Keywords: Autoantigens; MLH1; MTIF3; NUP50; PPIL2; Type 1 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / immunology
  • Autoimmune Diseases / immunology
  • Child
  • Child, Preschool
  • Cyclophilins / immunology
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Genotype
  • HLA-DQ beta-Chains / immunology*
  • Humans
  • Infant
  • Male
  • Mitochondrial Proteins / immunology
  • MutL Protein Homolog 1 / immunology
  • Young Adult


  • Autoantibodies
  • HLA-DQ beta-Chains
  • Mitochondrial Proteins
  • MutL Protein Homolog 1
  • Cyclophilins