Interleukin-2-inducible T-cell Kinase (ITK) Deficiency - Clinical and Molecular Aspects

Overview

Journal J Clin Immunol

Publisher Springer

Specialty Allergy & Immunology

Date 2014 Oct 24

PMID 25339095

Citations 48

Authors

Sujal Ghosh

Kirsten Bienemann

Kaan Boztug

Arndt Borkhardt

Affiliations

Soon will be listed here.

Abstract

In patients with underlying immunodeficiency, Epstein-Barr virus (EBV) may lead to severe immune dysregulation manifesting as fatal mononucleosis, lymphoma, lymphoproliferative disease (LPD), lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis (HLH) and dysgammaglobulinemia. Several newly discovered primary immunodeficiencies (STK4, CD27, MAGT1, CORO1A) have been described in recent years; our group and collaborators were able to reveal the pathogenicity of mutations in the Interleukin-2-inducible T-cell Kinase (ITK) in a cohort of nine patients with most patients presenting with massive EBV B-cell lymphoproliferation. This review summarizes the clinical and immunological findings in these patients. Moreover, we describe the functional consequences of the mutations and draw comparisons with the extensively investigated function of ITK in vitro and in the murine model.

Citing Articles

Multiple Tumors in a Patient with Interleukin-2-Inducible T-Cell Kinase Deficiency: A Case Report.

Di Filippo M, Tallone R, Muraca M, Pelanconi L, Faravelli F, Capra V Int J Mol Sci. 2024; 25(23).

PMID: 39684891 PMC: 11642095. DOI: 10.3390/ijms252313181.

Identification of potential biomarkers and drug of ischemic stroke in patients with COVID-19 through machine learning.

Wang S, Tai Y, Yang X, Li P, Wang H, Tan Y Heliyon. 2024; 10(20):e39039.

PMID: 39502238 PMC: 11536010. DOI: 10.1016/j.heliyon.2024.e39039.

Cancer Trends in Inborn Errors of Immunity: A Systematic Review and Meta-Analysis.

Fekrvand S, Abolhassani H, Esfahani Z, Fard N, Amiri M, Salehi H J Clin Immunol. 2024; 45(1):34.

PMID: 39466473 DOI: 10.1007/s10875-024-01810-w.

Inborn Errors of Immunity and Cytokine Storm Syndromes.

Reid W, Romberg N Adv Exp Med Biol. 2024; 1448:185-207.

PMID: 39117816 DOI: 10.1007/978-3-031-59815-9_14.

Efficacy of T-cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis.

Chiang S, Covill L, Tesi B, Campbell T, Schlums H, Nejati-Zendegani J Blood. 2024; 144(8):873-887.

PMID: 38958468 PMC: 11375501. DOI: 10.1182/blood.2024024499.

References

Khurana D, Arneson L, Schoon R, Dick C, Leibson P . Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. J Immunol. 2007; 178(6):3575-82. DOI: 10.4049/jimmunol.178.6.3575. View

Salzer E, Daschkey S, Choo S, Gombert M, Santos-Valente E, Ginzel S . Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27. Haematologica. 2012; 98(3):473-8. PMC: 3659923. DOI: 10.3324/haematol.2012.068791. View

Lee S, Chang H, Jang A, Park S, Park J, Uh S . The association of a single-nucleotide polymorphism of the IL-2 inducible T-cell Kinase gene with asthma. Ann Hum Genet. 2011; 75(3):359-69. DOI: 10.1111/j.1469-1809.2010.00637.x. View

Moshous D, Martin E, Carpentier W, Lim A, Callebaut I, Canioni D . Whole-exome sequencing identifies Coronin-1A deficiency in 3 siblings with immunodeficiency and EBV-associated B-cell lymphoproliferation. J Allergy Clin Immunol. 2013; 131(6):1594-603. DOI: 10.1016/j.jaci.2013.01.042. View

Serwas N, Cagdas D, Ban S, Bienemann K, Salzer E, Tezcan I . Identification of ITK deficiency as a novel genetic cause of idiopathic CD4+ T-cell lymphopenia. Blood. 2014; 124(4):655-7. PMC: 4110665. DOI: 10.1182/blood-2014-03-564930. View

Heslop H . How I treat EBV lymphoproliferation. Blood. 2009; 114(19):4002-8. PMC: 2774540. DOI: 10.1182/blood-2009-07-143545. View

Kosaka Y, Felices M, Berg L . Itk and Th2 responses: action but no reaction. Trends Immunol. 2006; 27(10):453-60. DOI: 10.1016/j.it.2006.08.006. View

Jain N, Miu B, Jiang J, McKinstry K, Prince A, Swain S . CD28 and ITK signals regulate autoreactive T cell trafficking. Nat Med. 2013; 19(12):1632-7. PMC: 4005518. DOI: 10.1038/nm.3393. View

Vargas L, Hamasy A, Nore B, Smith C . Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases. Scand J Immunol. 2013; 78(2):130-9. DOI: 10.1111/sji.12069. View

10.

van Montfrans J, Hoepelman A, Otto S, van Gijn M, van de Corput L, de Weger R . CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J Allergy Clin Immunol. 2011; 129(3):787-793.e6. PMC: 3294016. DOI: 10.1016/j.jaci.2011.11.013. View

11.

Abdollahpour H, Appaswamy G, Kotlarz D, Diestelhorst J, Beier R, Schaffer A . The phenotype of human STK4 deficiency. Blood. 2012; 119(15):3450-7. PMC: 3325036. DOI: 10.1182/blood-2011-09-378158. View

12.

Broussard C, Fleischacker C, Fleischecker C, Horai R, Chetana M, Venegas A . Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk. Immunity. 2006; 25(1):93-104. DOI: 10.1016/j.immuni.2006.05.011. View

13.

Readinger J, Schiralli G, Jiang J, Thomas C, August A, Henderson A . Selective targeting of ITK blocks multiple steps of HIV replication. Proc Natl Acad Sci U S A. 2008; 105(18):6684-9. PMC: 2365562. DOI: 10.1073/pnas.0709659105. View

14.

Hennig C, Ilginus C, Boztug K, Skokowa J, Marodi L, Szaflarska A . High-content cytometry and transcriptomic biomarker profiling of human B-cell activation. J Allergy Clin Immunol. 2013; 133(1):172-80.e1-10. DOI: 10.1016/j.jaci.2013.06.047. View

15.

Qi Q, Kannan A, August A . Tec family kinases: Itk signaling and the development of NKT αβ and γδ T cells. FEBS J. 2011; 278(12):1970-9. DOI: 10.1111/j.1742-4658.2011.08074.x. View

16.

Felices M, Berg L . The Tec kinases Itk and Rlk regulate NKT cell maturation, cytokine production, and survival. J Immunol. 2008; 180(5):3007-18. DOI: 10.4049/jimmunol.180.5.3007. View

17.

Schaeffer E, Debnath J, Yap G, McVicar D, Liao X, Littman D . Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity. Science. 1999; 284(5414):638-41. DOI: 10.1126/science.284.5414.638. View

18.

Gomez-Rodriguez J, Wohlfert E, Handon R, Meylan F, Wu J, Anderson S . Itk-mediated integration of T cell receptor and cytokine signaling regulates the balance between Th17 and regulatory T cells. J Exp Med. 2014; 211(3):529-43. PMC: 3949578. DOI: 10.1084/jem.20131459. View

19.

Stevenson P, Efstathiou S . Immune mechanisms in murine gammaherpesvirus-68 infection. Viral Immunol. 2005; 18(3):445-56. DOI: 10.1089/vim.2005.18.445. View

20.

Hussain A, Yu L, Faryal R, Mohammad D, Mohamed A, Smith C . TEC family kinases in health and disease--loss-of-function of BTK and ITK and the gain-of-function fusions ITK-SYK and BTK-SYK. FEBS J. 2011; 278(12):2001-10. DOI: 10.1111/j.1742-4658.2011.08134.x. View