Abstract 2767

Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, incompletely penetrant, childhood disorder associated with biallelic loss-of-function mutations of SMARCAL1 (swi/snf-related matrix-associated actin-dependent regulator of chromatin, subfamily-a-like-1) gene. The SMARCAL1 gene encodes for the DNA annealing helicase although it is unknown why this impairment results in skeletal dysplasia, renal dysfunction, and T-cell lymphopenia. The representation of T-cell subsets in SIOD patients is further characterized by a high proportion of memory (CD45RACD45RO+) T cells, however, the etiology of T-cell immunodeficiency has not been elucidated. Here, we demonstrate that T cells in individuals affected by SIOD express markedly reduced surface levels of IL-7 receptor alpha chain (CD127) as compared to their unaffected sibling or normal individuals. In contrast, the alpha-chain component of the IL-2 receptor (CD25) was expressed normally. This reduction in IL-7 receptor alpha chain was observed in all T-cell subsets including naïve T cells. This suggests that the origin of the IL-7 receptor alpha chain deficiency is likely intrathymic, rather than occurring after emigration to the periphery. In addition, T cells from SIOD patients were less responsive to stimulation with IL-7, indicating a loss of functional receptor. From these observations, we propose the lack of functional IL-7 receptor expression in T cells, and possibly their earlier progenitors, may have restricted T-cell development in SIOD patients. The mechanism for reduced IL-7 receptor expression is currently under investigation.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.