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

19 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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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