Interferon gamma- receptor deficiency
Overview
Interferon gamma receptor (IFNg) deficiency (medical condition): A rare form of primary immunodeficiency which results in a high risk of severe, recurring infections such as mycobacterial infections.
The functional Interferon gamma receptor is composed of two 90 kDa IFNgR1 proteins and two 62 kDa IFNgR2 proteins . The human IFNgR1 gene contains seven exons, and is located on chromosome 6. The extracellular portion of IFNgR1 contains the IFNg ligand-binding domain; the intracellular portion contains domains necessary for signal transduction and receptor recycling. The IFNgR2 gene also contains seven exons, and is located on human chromosome 21. The intracellular IFNgR2 domain is necessary for signal transduction.
The disease occur as a result of mutation in either the IFNgR1 or the IFNgR2 proteins.
Symptoms
- Recurring mycobacterial infection
- Recurring intracellular infections
- Tuberculosis following TB immunization
Causes
The existence of a genetic component to human mycobacterial disease susceptibility had long been postulated. Now we know that a variety of IFNgR mutations are associated with complete or partial IFNgR deficiency. They include nonsense and splice mutations and frameshift insertions and deletions. All result in a premature stop codon upstream from the segment encoding the transmembrane and the extracellular ligand-binding domain, either precluding cell surface expression of the receptors at the cell surface or by disrupting the IFNg binding site without affecting surface expression respectively. Phenotype-to-genotype correlations are being established as more affected individuals are identified. However, for IFNgR defficiency, the phenotype appears to depend less on which gene (IFNgR1 vs IFNgR2) is mutated, but rather on the extent to which the mutation reduces IFNg responsiveness.
Diagnosis
Sophisticated laboratory tests measure the amount of interferon gamma in the blood and show the patient's white blood cells respond poorly, or not at all, to interferon gamma. Depending on whether the patient has complete or partial IFNGR deficiency, the blood will have either very high or very low levels of interferon gamma. Genetic testing can determine whether the patient has mutations that cause IFNgR deficiency.
Resources
http://www.bio.davidson.edu/courses/immunology/students/spring2006/v_alvarez/ifngrdeficiency.html