IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach.

Abstract

Mutations in the IL-2-inducible T-cell kinase gene have recently been shown to cause an autosomal recessive fatal Epstein Barr virus (EBV) associated lymphoproliferation. We report 3 cases from a single family who presented with EBV-positive B-cell proliferation diagnosed as Hodgkin's lymphoma. Single nucleotide polymorphism array-based genome-wide linkage analysis revealed IL-2-inducible T-cell kinase as a candidate gene for this disorder. All 3 patients harbored the same novel homozygous nonsense mutation C1764G which causes a premature stop-codon in the kinase domain. All cases were initially treated with chemotherapy. One patient remains in durable remission, the second patient subsequently developed severe hemophagocytic lymphohistiocytosis with multi-organ failure and died, and the third patient underwent a successful allogeneic bone marrow transplantation. IL-2-inducible T-cell kinase deficiency underlies a new primary immune deficiency which may account for part of the spectrum of Epstein Barr virus related lymphoproliferative disorders which can be successfully corrected by bone marrow transplantation.

• Authors: Polina Stepensky, Michael Weintraub, Asaf Yanir, Shoshana Revel-Vilk, Frank Krux, Kirsten Huck, Rene M Linka, Avraham Shaag, Orly Elpeleg, Arndt Borkhardt, Igor B Resnick
• Journal: Haematologica (Haematologica) Vol. 96 Issue 3 Pg. 472-6 (Mar 2011) ISSN: 1592-8721 [Electronic] Italy
• PMID: 21109689 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Codon, Nonsense
• Protein-Tyrosine Kinases
• emt protein-tyrosine kinase

Topics

• Antineoplastic Agents (administration & dosage, therapeutic use)
• B-Lymphocytes (immunology, pathology)
• Bone Marrow Transplantation (immunology)
• Child, Preschool
• Codon, Nonsense
• Death
• Disease-Free Survival
• Epstein-Barr Virus Infections (complications, genetics, immunology, pathology, therapy)
• Female
• Herpesvirus 4, Human (growth & development)
• Hodgkin Disease (etiology, genetics, immunology, pathology, therapy)
• Homozygote
• Humans
• Lymphocyte Activation (genetics, immunology)
• Lymphohistiocytosis, Hemophagocytic (mortality, pathology)
• Male
• Pedigree
• Protein-Tyrosine Kinases (genetics, immunology)
• Remission Induction
• Transplantation, Homologous (immunology)