Hypomorphic Janus kinase 3 mutations result in a spectrum of immune defects, including partial maternal T-cell engraftment

Federica Cattaneo, Mike Recher, Stefania Masneri, Sachin N. Baxi, Claudia Fiorini, Francesca Antonelli, Christian A. Wysocki, Jose G. Calderon, Hermann Eibel, Angela R Smith, Francisco A. Bonilla, Erdyni Tsitsikov, Silvia Giliani, Luigi D. Notarangelo, Sung Yun Pai

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Background: Mutations in Janus kinase 3 (JAK3) are a cause of severe combined immunodeficiency, but hypomorphic JAK3 defects can result in a milder clinical phenotype, with residual development and function of autologous T cells. Maternal T-cell engraftment is a common finding in infants with severe combined immunodeficiency but is not typically observed in patients with residual T-cell development. Objective: We sought to study in detail the molecular, cellular, and humoral immune phenotype and function of 3 patients with hypomorphic JAK3 mutations. Methods: We analyzed the distribution and function of T and B lymphocytes in 3 patients and studied the in vitro and in vivo responses of maternal T lymphocytes in 1 patient with maternal T-cell engraftment and residual production of autologous T lymphocytes. Results: B cells were present in normal numbers but with abnormal distribution of marginal zone-like and memory B cells. B-cell differentiation to plasmablasts in vitro in response to CD40 ligand and IL-21 was abolished. In 2 patients the T-cell repertoire was moderately restricted. Surprisingly, 1 patient showed coexistence of maternal and autologous T lymphocytes. By using an mAb recognizing the maternal noninherited HLA-A2 antigen, we found that autologous cells progressively accumulated in vivo but did not compete with maternal cells in vitro. Conclusion: The study of 3 patients with hypomorphic JAK3 mutations suggests that terminal B-cell maturation/differentiation requires intact JAK3 function, even if partially functioning T lymphocytes are present. Maternal T-cell engraftment can occur in patients with JAK3 mutations despite the presence of autologous T cells.

Original languageEnglish (US)
Pages (from-to)1136-1145
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Issue number4
StatePublished - Apr 2013


  • Severe combined immunodeficiency
  • cytokine signaling
  • maternal engraftment


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