A case of aberrant CD8 T cell-restricted IL-7 signaling with a Janus kinase 3 defect-associated atypical severe combined immunodeficiency
| Autor: | Guorong Liu, Ramsay L. Fuleihan, Jenna R.E. Bergerson, Bridget M. Simpson, Aaruni Khanolkar, Jeffrey D. Wilks, Edward Caparelli, Dawn A. Kirschmann |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lymphocyte T cell Immunology CD8-Positive T-Lymphocytes 03 medical and health sciences 0302 clinical medicine Exome Sequencing STAT5 Transcription Factor Medicine Cytotoxic T cell Humans Phosphorylation 030203 arthritis & rheumatology Severe combined immunodeficiency Cell growth business.industry Janus kinase 3 Interleukin-7 Infant Newborn Infant Janus Kinase 3 medicine.disease 030104 developmental biology medicine.anatomical_structure Phenotype Mutation Female Severe Combined Immunodeficiency Cord Blood Stem Cell Transplantation Stem cell business CD8 Signal Transduction |
| Zdroj: | Immunologic research. 68(1) |
| ISSN: | 1559-0755 |
| Popis: | 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 (T-B+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 (T-B+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 T-SCID. Immunological assessments revealed a T-B+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. |
| Databáze: | OpenAIRE |
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