|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 May 2001, Vol. 97, No. 9, pp. 2688-2694
IMMUNOBIOLOGY
Missense mutation of the interleukin-12 receptor  1
chain-encoding gene is associated with impaired immunity against
Mycobacterium avium complex infection
Tatsunori Sakai,
Masao Matsuoka,
Manabu Aoki,
Kisato Nosaka, and
Hiroaki Mitsuya
From the Department of Immunopathophysiology and
Internal Medicine II, Kumamoto University School of Medicine; the
Laboratory of Virus Immunology, Research Center for AIDS, Institute for
Virus Research, Kyoto University, Japan; and the Experimental
Retrovirology Section, Medicine Branch, Division of Clinical Sciences,
National Cancer Institute, Bethesda, MD.
Interleukin-12 (IL-12) plays an important role in the production of
interferon gamma (IFN- ) and is essential for protection against
intracellular pathogens such as Mycobacterium and
Salmonella. A 31-year-old man had disseminated
Mycobacterium avium complex (MAC) infection. The production
of IFN- by peripheral blood mononuclear cells stimulated with
phytohemagglutinin (PHA-PBMCs) was found severely impaired (40.7 pg/mL
compared with 833 ± 289 pg/mL for the patient's and healthy
subjects' (n = 3) PHA- PBMCs, respectively), and the
patient's PHA-PBMCs completely lacked surface IL-12 receptor  1
(IL-12R1) chain. The IL-12R1 gene transcript in his PHA-PBMCs had an R213W substitution in each allele. Family history showed that both parents were heterozygotes in the R213W substitution. Transfection of a human embryonal kidney cell line 293 (HEKC293) with
wild-type IL-12R1wt gene led to cell surface IL-12R1
expression; however, no expression was seen in HEKC293 transfected with
the mutated IL-12R1R213W gene. The
IL-12R1 gene transcript, but no IL-12R1 protein, was
detected in PHA-PBMCs and T cells, suggesting a post-translational
event(s), most likely a shortened turnover of the protein. The R213W
substitution was not detected in the cells of 32 healthy persons or of
25 patients with tuberculosis or MAC infection. Six amino acid
substitutions (Q214R, M365T, G378R, H438Y, A525T, and G594E) were
identified, but the incidences of such substitutions were not
significantly different between the groups. The Q214R substitution is
reportedly linked to IL-12R1 deficiency; however, the study showed
that 19 and 10 of 57 Japanese and 6 and 4 of 33 healthy white persons
were heterozygous and homozygous for Arg-214, respectively,
suggesting that the Q214R substitution represents a
polymorphism and is not related to IL-12R1 deficiency but that
the R213W substitution is responsible for IL-12R1 deficiency.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Marquet, O. Doumbo, S. Cabantous, B. Poudiougou, L. Argiro, I. Safeukui, S. Konate, S. Sissoko, E. Chevereau, A. Traore, et al.
A functional promoter variant in IL12B predisposes to cerebral malaria
Hum. Mol. Genet.,
July 15, 2008;
17(14):
2190 - 2195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Khader, S. Partida-Sanchez, G. Bell, D. M. Jelley-Gibbs, S. Swain, J. E. Pearl, N. Ghilardi, F. J. deSauvage, F. E. Lund, and A. M. Cooper
Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection
J. Exp. Med.,
July 10, 2006;
203(7):
1805 - 1815.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. van de Vosse, R. A. de Paus, J. T. van Dissel, and T. H.M. Ottenhoff
Molecular complementation of IL-12R{beta}1 deficiency reveals functional differences between IL-12R{beta}1 alleles including partial IL-12R{beta}1 deficiency
Hum. Mol. Genet.,
December 15, 2005;
14(24):
3847 - 3855.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Takahashi, M. Akahoshi, A. Matsuda, K. Ebe, N. Inomata, K. Obara, T. Hirota, K. Nakashima, M. Shimizu, M. Tamari, et al.
Association of the IL12RB1 promoter polymorphisms with increased risk of atopic dermatitis and other allergic phenotypes
Hum. Mol. Genet.,
November 1, 2005;
14(21):
3149 - 3159.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Sanchez, S. Morales, L. Paco, M. A. Lopez-Nevot, C. Hidalgo, J. Jimenez-Alonso, B. Torres, M. A. Gonzalez-Gay, J. L. Callejas, N. Ortego-Centeno, et al.
Interleukin 12 (IL12B), interleukin 12 receptor (IL12RB1) and interleukin 23 (IL23A) gene polymorphism in systemic lupus erythematosus
Rheumatology,
September 1, 2005;
44(9):
1136 - 1139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-J. Koh, O. J. Kwon, E. J. Kim, K. S. Lee, C.-S. Ki, and J. W. Kim
NRAMP1 Gene Polymorphism and Susceptibility to Nontuberculous Mycobacterial Lung Diseases
Chest,
July 1, 2005;
128(1):
94 - 101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H Ohyama, K Ogata, K Takeuchi, M Namisato, Y Fukutomi, F Nishimura, H Naruishi, T Ohira, K Hashimoto, T Liu, et al.
Polymorphism of the 5' flanking region of the IL-12 receptor {beta}2 gene partially determines the clinical types of leprosy through impaired transcriptional activity
J. Clin. Pathol.,
July 1, 2005;
58(7):
740 - 743.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Fieschi, M. Bosticardo, L. de Beaucoudrey, S. Boisson-Dupuis, J. Feinberg, O. F. Santos, J. Bustamante, J. Levy, F. Candotti, and J.-L. Casanova
A novel form of complete IL-12/IL-23 receptor {beta}1 deficiency with cell surface-expressed nonfunctional receptors
Blood,
October 1, 2004;
104(7):
2095 - 2101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. D. Russell, Q. Yan, G. Fan, A. P. Khalifah, D. K. Bishop, S. L. Brody, and M. J. Walter
IL-12 p40 Homodimer-Dependent Macrophage Chemotaxis and Respiratory Viral Inflammation Are Mediated through IL-12 Receptor {beta}1
J. Immunol.,
December 15, 2003;
171(12):
6866 - 6874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Andrews and K. E. Sullivan
Infections in Patients with Inherited Defects in Phagocytic Function
Clin. Microbiol. Rev.,
October 1, 2003;
16(4):
597 - 621.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Fieschi, S. Dupuis, E. Catherinot, J. Feinberg, J. Bustamante, A. Breiman, F. Altare, R. Baretto, F. Le Deist, S. Kayal, et al.
Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor {beta}1 Deficiency: Medical and Immunological Implications
J. Exp. Med.,
February 17, 2003;
197(4):
527 - 535.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Cleary, W. Tu, A. Enright, T. Giffon, R. Dewaal-Malefyt, K. Gutierrez, and D. B. Lewis
Impaired Accumulation and Function of Memory CD4 T Cells in Human IL-12 Receptor {beta}1 Deficiency
J. Immunol.,
January 1, 2003;
170(1):
597 - 603.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
