A case of aberrant CD8 T cell–restricted IL-7 signaling with a Janus kinase 3 defect–associated atypical severe combined immunodeficiency

Aaruni Khanolkar*, Jeffrey D. Wilks, Guorong Liu, Bridget M. Simpson, Edward A. Caparelli, Dawn A. Kirschmann, Jenna Bergerson, Ramsay L. Fuleihan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Severe combined immunodeficiency (SCID) disorders compromise lymphocyte numbers and/or function. One subset of SCID typically affects T cell and Natural Killer (NK) cell development in tandem (TB+NK) due to mutations arising in the genes encoding the common γ chain or Janus Kinase 3 (JAK3). In rare circumstances, mutations in the JAK3 gene have been reported to cause atypical SCID that selectively affects T cells (TB+NK+). Here we describe a case involving a female infant who was referred to our institution on day nine of life following an abnormal newborn screen result for TSCID. Immunological assessments revealed a TB+NK+ phenotype and molecular analyses, including whole exome sequencing, identified compound heterozygous JAK3 variants (R117C and E658K). Pre-transplant phosflow analyses revealed a persistent IL-7 signaling defect, based on phospho-STAT5 measurements, only in CD8 but not CD4 T cells. Intriguingly, phospho-STAT5 signals in response to IL-2 stimulation were not affected in either CD4 or CD8 T cells. The pre-transplant clinical course was unremarkable, and the patient received a cord-blood stem cell transplant on day 716 of life. Post-transplant monitoring revealed that despite normalization of lymphocyte counts, the CD8 T cell-restricted IL-7 signaling defect was still evident at day 627 post-transplant (phospho-STAT5 signal in CD8 T cells was > 60% reduced compared with CD4 T cells). The post-transplant clinical course has also been complicated by identification of autoimmune responses and likely GVHD-induced ichthyosis. To the best of our knowledge, this report represents the third case of JAK3-associated atypical SCID reported in the literature.

Original languageEnglish (US)
Pages (from-to)13-27
Number of pages15
JournalImmunologic Research
Issue number1
StatePublished - Feb 1 2020


  • Atypical-SCID
  • CD8 T cells
  • IL-7
  • IL-7R
  • JAK3
  • pSTAT5

ASJC Scopus subject areas

  • Immunology


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