Of genes and phenotypes: The immunological and molecular spectrum of combined immune deficiency. Defects of the γc-JAK3 signaling pathway as a model

Luigi D. Notarangelo, Silvia Giliani, Cinzia Mazza, Cinzia Mazza, Patrizia Mella, Gianfranco Savoldi, Carmen Rodriguezpérez, Evelina Mazzolari, Maurilia Fiorini, Marzia Duse, Alessandro Plebani, Alberto G. Ugazio, Mauno Vihinen, Fabio Candotti, Richard F. Schumacher

Research output: Contribution to journalArticle

Abstract

Cytokines play a major role in lymphoid development. Defects of the common gamma chain (γc) or of the JAK3 protein in humans have been shown to result in a severe combined immune deficiency (SCID), with a profound defect in T and natural killer (NK)-cell development, whereas B-cell generation is apparently unaffected (T-B+NK- SCID). While extensive molecular and biochemical analysis of these patients has been instrumental in understanding better the biological properties of the γc and JAK3 protein, an unexpected phenotypic heterogeneity of γc and JAK3 deficiency has emerged, indicating the need for appropriate and extensive investigations even in patients with atypical presentations. At the same time, characterization of the defects has been instrumental in the development of novel therapeutic approaches, from in utero hematopoietic stem cell transplantation to gene therapy.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalImmunological Reviews
Volume178
Publication statusPublished - 2000

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ASJC Scopus subject areas

  • Immunology

Cite this

Notarangelo, L. D., Giliani, S., Mazza, C., Mazza, C., Mella, P., Savoldi, G., Rodriguezpérez, C., Mazzolari, E., Fiorini, M., Duse, M., Plebani, A., Ugazio, A. G., Vihinen, M., Candotti, F., & Schumacher, R. F. (2000). Of genes and phenotypes: The immunological and molecular spectrum of combined immune deficiency. Defects of the γc-JAK3 signaling pathway as a model. Immunological Reviews, 178, 39-48.