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Lack of IL7Ra expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD). Clinical immunology Sanyal, M., Morimoto, M., Baradaran-Heravi, A., Choi, K., Kambham, N., Jensen, K., Dutt, S., Dionis-Petersen, K. Y., Liu, L. X., Felix, K., Mayfield, C., Dekel, B., Bokenkamp, A., Fryssira, H., Guillen-Navarro, E., Lama, G., Brugnara, M., Lücke, T., Olney, A. H., Hunley, T. E., Polat, A. I., Yis, U., Bogdanovic, R., Mitrovic, K., Berry, S., Najera, L., Najafian, B., Gentile, M., Nur Semerci, C., Tsimaratos, M., Lewis, D. B., Boerkoel, C. F. 2015; 161 (2): 355-365

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 (IL7Ra) 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 IL7Ra expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients.

View details for DOI 10.1016/j.clim.2015.10.005

View details for PubMedID 26499378