Hyperimmunoglobulin E syndrome and tyrosine kinase 2 deficiency.
OBJECTIVE
The purpose of the review is to provide recent insight into the pathogenesis and pathophysiology of hyperimmunoglobulin E syndrome.


RESULTS
We recently identified a homozygous four base-pair deletion in the coding region of the tyrosine kinase 2 gene in a hyperimmunoglobulin E syndrome patient who exhibited susceptibility to intracellular bacteria.


CONCLUSIONS
Hyperimmunoglobulin E syndrome is a primary immunodeficiency characterized by recurrent staphylococcal skin abscesses and pneumonia, and elevated serum immunoglobulin E. This syndrome is subdivided into types 1 and 2. Type 1 displays abnormalities in multiple systems, including the skeletal/dental and immune systems, whereas type 2 abnormalities are confined to the immune system. We recently identified a homozygous mutation in the tyrosine kinase 2 gene in a type 2 patient. Analyses of cytokine responses in the patient's cells revealed that the tyrosine kinase 2 deficiency had resulted in severe impairment of the signal transduction for multiple cytokines, including interleukin-6, -10, -12 and -23, and interferon-alpha/beta. The cytokine signals were successfully restored by transducing the intact tyrosine kinase 2 gene. Thus, tyrosine kinase 2 plays obligatory roles in human immunity. Based on this finding, we propose that hyperimmunoglobulin E syndrome is a primary immunodeficiency caused by genetic alterations leading to the defect in multiple cytokine signals.
Minegishi
Yoshiyuki
Y
Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. yminegishi.mbch@tmd.ac.jp
Karasuyama
Hajime
H
D016207:Cytokines / Q000235:genetics / Q000276:immunology; D006801:Humans; D007589:Job Syndrome / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D053634:TYK2 Kinase / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D014161:Transduction, Genetic
D016207:Cytokines; D053634:TYK2 Kinase; C070139:TYK2 protein, human