Partial Interferon-γReceptor Deficiencyin Patients with Disseminated Tuberculosis

Background : Interferon-gamma (IFN- ) is essential in the immune response to mycobacterial infections, and a complete or partial deficiency in the IFN- receptor 1 (IFN R1) or the IFN- receptor 2 (IFN R2) have been reported to confer susceptibility to a disseminated infection with nontuberculous mycobacteria. However, similar mutations in the IFN- receptor have not been specifically examined in the patients with clinical tuberculosis. Methods : This study searched for mutations in the IFN- receptor gene that resulted in a partial IFN- receptor deficiency in six patients with disseminated tuberculosis. The previously identified IFN R1 and IFN R2 coding regions were sequenced after amplification.Results : There was no partial IFN R1 deficiency including a homozygous recessive missense mutation causing an amino-acid substitution in the extracellular domain of the receptor (I87T) and a hotspot for small deletions (818delT, 818del4, 818insA) found in any of the patients. In addition, a partial IFN R2 deficiency of the homozygous missense mutation (R114C) was not found in any of the patients.Conclusion : Genetic defects causing a partial IFN- receptor deficiency were not identified in our patients with disseminated tuberculosis. (Tuberc Respir Dis 2005; 58:11-17)

keywords: Tuberculosis, Genetic predisposition to disease, Interferon receptors, Point mutation

Reference

Rouillon A. Tuberculosis in developing countries,

(1998) Genetics pulmonary medicine: 3. genetic susceptibility to tuberculosis in human po�,

(2001) Immune deficiency presenting as my ?cobacterial infection,

(2002) Inherited disorders of IL-12- and IFN-γ-mediated immunity : a molecular genetics update,

(2003) Susceptibility to mycobacterial infections the importance of host genetics. ,

Bloom BR. An essential role for interferon ？ in resistance to Mycobacterium tuberculosis infection. J Exp Med 1993,

(2002) Host susceptibility factors in mycobacterial infection : genetics and body mor?photype. ,

(1998) The host immune response to tuberculosis. ,

(1999) Viral infections in interferon-γ receptor deficiency,

10.

(1996) A mutation in the interferon-？-receptor gene and susceptibility to mycobacterial infection. ,

11.

(2001) Recurrent Mycobacterium avium osteomyelitis associated with a novel dominant in terferon gamma receptor mutation,

12.

(1996) Newport M, et al. Interferon-？-receptor ficiency in an infant with fatal bacille Calmette- Guerin infection.,

13.

(2000) Partial interferon-γ receptor signaling chain deficiency in a patient with bacille Calmette-Guerin and Mycobacterium absce,

14.

(1998) Holland SM. Mutation in the signal- transducing chain of the interferon-？ receptor and susceptibility to mycobacterial infection. ,

15.

(1973) Importance of thymus-derived lymphocytes in cell-mediated immunity to infection,

16.

(jexpmed1983) Protection against Mycobac terium tuberculosis infection by adoptive immuno requirement for T cell-deficient recipients,

17.

(1997) et al. Partial interferon-？ receptor 1 deficiency in a child with tuberculoid bacillus Calmette-Guerin infection and a sibling with clinical tuberculosis. ,

18.

(1993) Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection,

19.

(1993) Multiple defects of immune cell function in mice with disrupted interferon-γ genes,

20.

(jexpmed1993) Mice that lack the interferon-γ re ceptor have profoundly altered responses to infection with Bacillus Calmette-Guerin and subsequent ch allenge with lipopolysaccharide,

21.

(2002) The functional and genetic defects of IFN-γ receptor in the patients with tuberculosis,

22.

(1999) The priming effect of IFN-γ and numbers of IFN-γ receptors in patients with chronic refractory tuberculosis,

바로가기메뉴

Article Contents

Vol.58 No.1

Partial Interferon-γReceptor Deficiencyin Patients with Disseminated Tuberculosis

Abstract

Reference

Tuberculosis & Respiratory Diseases