Interleukin-7 and soluble Interleukin-7 receptor levels in type 1 diabetes - Impact of IL7RA polymorphisms, HLA risk genotypes and clinical features

Clin Immunol. 2022 Feb:235:108928. doi: 10.1016/j.clim.2022.108928. Epub 2022 Jan 19.

Abstract

High soluble IL-7 receptor (sIL-7R) serum levels and associated single nucleotide polymorphisms in the IL7RA gene were found in autoimmune diseases including type 1 diabetes. Further determinants on sIL-7R and IL-7 availability as well as changes during type 1 diabetes disease course remain elusive. Here we performed multiparameter analysis to identify influential genetic and disease-associated factors on sIL-7R and IL-7 serum levels during type 1 diabetes disease course (239 children) and in healthy controls (101 children). We found higher sIL-7R serum concentrations at type 1 diabetes onset and decreasing levels during therapy whereas IL-7 was only higher in long term patients as compared to controls. Multiple linear regression analyses revealed several factors, including IL7RA SNP rs6897932 and HLA risk haplotypes, influencing sIL-7R levels but not IL-7, which was solely associated with the sIL-7R. This study revealed unexpected complexity in the regulation of the sIL-7R but not for IL-7.

Keywords: Autoimmunity; HLA; IL-7; IL7RA SNPs; Soluble IL-7 receptor; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Diabetes Mellitus, Type 1 / genetics*
  • Genetic Predisposition to Disease
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Interleukin-7 / genetics
  • Interleukin-7 / metabolism*
  • Polymorphism, Genetic*
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / metabolism*

Substances

  • Histocompatibility Antigens Class I
  • IL7 protein, human
  • Interleukin-7
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain