Lack of IL7R alpha expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)

Sanyal M., Morimoto M., Baradaran-Heravi A., Choi K., Kambham N., Jensen K., ...More

CLINICAL IMMUNOLOGY, no.2, pp.355-365, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2015
  • Doi Number: 10.1016/j.clim.2015.10.005
  • Journal Name: CLINICAL IMMUNOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.355-365
  • Keywords: SIOD, T-cell immunodeficiency, IL7R alpha, CD127, CpG, Promoter DNA methylation, SPONDYLOEPIPHYSEAL DYSPLASIA, NEPHROTIC SYNDROME, OF-FUNCTION, SMARCAL1, GENE, DEFICIENCY, MUTATIONS, PROTEIN
  • Dokuz Eylül University Affiliated: Yes

Abstract

Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7R alpha) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7R alpha expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients. (C) 2015 Elsevier Inc. All rights reserved.