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

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

doi:10.3324/haematol.2010.033910

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

Haematologica. 2011 Mar;96(3):472-6. doi: 10.3324/haematol.2010.033910. Epub 2010 Nov 25.

Authors

Polina Stepensky¹, Michael Weintraub, Asaf Yanir, Shoshana Revel-Vilk, Frank Krux, Kirsten Huck, Rene M Linka, Avraham Shaag, Orly Elpeleg, Arndt Borkhardt, Igor B Resnick

Affiliation

¹ Pediatric Hematology-Oncology, Hadassah Hebrew University Medical Center, PO Box 12000, Jerusalem 91120, Israel. polina@hadassah.org.il

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.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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