Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)

Mrinmoy Sanyal, Marie Morimoto, Alireza Baradaran-Heravi, Kunho Choi, Neeraja Kambham, Kent Jensen, Suparna Dutt, Kira Y. Dionis-Petersen, Lan Xiang Liu, Katie Felix, Christy Mayfield, Benjamin Dekel, Arend Bokenkamp, Helen Fryssira, Encarna Guillen-Navarro, Giuliana Lama, Milena Brugnara, Thomas Lücke, Ann Haskins Olney, Tracy E. HunleyAyse Ipek Polat, Uluc Yis, Radovan Bogdanovic, Katarina Mitrovic, Susan Berry, Lydia Najera, Behzad Najafian, Mattia Gentile, C. Nur Semerci, Michel Tsimaratos, David B. Lewis, Cornelius F. Boerkoel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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 (IL7Rα) 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 IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients.

Original languageEnglish (US)
Pages (from-to)355-365
Number of pages11
JournalClinical Immunology
Issue number2
StatePublished - Dec 1 2015

Bibliographical note

Funding Information:
We would like to thank all of the patients and family members who have contributed to this study. This work was supported in part by grants from the Dana Foundation (C.F.B. and D.B.L.); the Burroughs Wellcome Foundation (1003400) (C.F.B.); the Association Autour D'Emeric et D'Anthony (C.F.B.); the Michael Smith Foundation for Health Research ((CI-SCH-O1899(07-1)) (C.F.B.); the Little Giants Foundation (C.F.B.); the Child & Family Research Institute of British Columbia Children's Hospital (C.F.B.); and the Asociacion Española de Displasias Oseas Minoritarias (C.F.B.). M.M. was supported by a Four Year Doctoral Fellowship from the University of British Columbia. C.F.B. is a scholar of the Michael Smith Foundation for Health Research and a Clinical Investigator of the Child & Family Research Institute. We would like to thank BioServe (Beltsville, MD) for assistance with recruiting age-matched, sex-matched individuals for the unaffected control blood samples.

Publisher Copyright:
© 2015 Elsevier Inc.


  • CD127
  • CpG
  • IL7Rα
  • Promoter DNA methylation
  • SIOD
  • T-cell immunodeficiency


Dive into the research topics of 'Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)'. Together they form a unique fingerprint.

Cite this