High Heritability of Antimycobacterial Immunity in an Area of Hyperendemicity for Tuberculosis Disease

被引：49

作者：

Cobat, Aurelie ^{[1
,2
]}

Gallant, Caroline J. ^{[3
,4
,5
]}

Simkin, Leah ^{[3
,4
,5
]}

Black, Gillian F. ^{[6
]}

Stanley, Kim ^{[6
]}

Hughes, Jane ^{[8
]}

Doherty, T. Mark ^{[10
]}

Hanekom, Willem A. ^{[8
]}

Eley, Brian ^{[9
]}

Beyers, Nulda ^{[7
]}

Jais, Jean-Philippe ^{[2
]}

van Helden, Paul ^{[6
]}

Abel, Laurent ^{[1
,2
,11
]}

Hoal, Eileen G. ^{[6
]}

Alcais, Alexandre ^{[1
,2
,11
]}

Schurr, Erwin ^{[3
,4
,5
]}

机构：

[1] Inst Natl Sante & Rech Med, Lab Human Genet Infect Dis, Necker Branch, Paris, France

[2] Univ Paris 05, Necker Med Sch, Paris, France

[3] McGill Univ, McGill Ctr Study Host Resistance, Montreal, PQ, Canada

[4] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[5] McGill Univ, Dept Med, Montreal, PQ, Canada

[6] Fac Hlth Sci, MRC Ctr Mol & Cellular Biol, DST NRF Ctr Excellence Biomed TB Res, Tygerberg, South Africa

[7] Univ Stellenbosch, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Fac Hlth Sci, ZA-7505 Tygerberg, South Africa

[8] Univ Cape Town, S African Vaccine Initiat, Inst Infect Dis & Mol Med, Fac Hlth Sci, ZA-7700 Rondebosch, South Africa

[9] Univ Cape Town, Paediat Infect Dis Unit, Red Cross Childrens Hosp, Sch Child & Adolescent Hlth, ZA-7700 Rondebosch, South Africa

[10] Statens Serum Inst, DK-2300 Copenhagen, Denmark

[11] Rockefeller Univ, Lab Human Genet Infect Dis, Rockefeller Branch, New York, NY 10021 USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2010年 / 201卷 / 01期

基金：

加拿大健康研究院;

关键词：

MYCOBACTERIUM-TUBERCULOSIS; CHROMOSOME-6; TRANSMISSION; PHENOTYPES; INFECTION; AFRICA; TWINS; GENE;

D O I：

10.1086/648611

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Human antimycobacterial immunity is a critical component of tuberculosis (TB) pathogenesis that is often used to infer the presence of TB infection. We report high heritability (>50%) for in vitro secretion of tumor necrosis factor alpha and interferon gamma (IFN-gamma), and the frequency of antigen-specific IFN-gamma(+)CD4(+) and IFN-gamma(+)CD8(+) cells in the response of whole blood to mycobacterial challenge. In principal component analysis, the first 3 components explain 78% of the overall variance consistent with the effect of pleiotropic regulatory genes of human antimycobacterial immunity. These results directly demonstrate the pivotal role played by host genetics in quantitative measures of antimycobacterial immunity underlying immune diagnosis of TB infection.

引用

页码：15 / 19

页数：5

共 15 条

[1] Factors of insulin resistance syndrome-related phenotypes are linked to genetic locations on chromosomes 6 and 7 in nondiabetic Mexican-Americans [J].

Arya, R ;

Blangero, J ;

Williams, K ;

Almasy, L ;

Dyer, TD ;

Leach, RJ ;

O'Connell, P ;

Stern, MP ;

Duggirala, R .

DIABETES, 2002, 51 (03) :841-847

[2] EQUIVALENCE OF THE MIXED AND REGRESSIVE MODELS FOR GENETIC-ANALYSIS .1. CONTINUOUS TRAITS [J].

DEMENAIS, FM ;

BONNEY, GE .

GENETIC EPIDEMIOLOGY, 1989, 6 (05) :597-617

[3] Genetic regulation of acquired immune responses to antigens of Mycobacterium tuberculosis:: a study of twins in West Africa [J].

Jepson, A ;

Fowler, A ;

Banya, W ;

Singh, M ;

Bennett, S ;

Whittle, H ;

Hill, AVS .

INFECTION AND IMMUNITY, 2001, 69 (06) :3989-3994

[4] Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: An update [J].

Pai, Madhukar ;

Zwerling, Alice ;

Menzies, Dick .

ANNALS OF INTERNAL MEDICINE, 2008, 149 (03) :177-184

[5] Association between tuberculosis and a polymorphic NFκB binding site in the interferon γ gene [J].

Rossouw, M ;

Nel, HJ ;

Cooke, GS ;

van Helden, PD ;

Hoal, EG .

LANCET, 2003, 361 (9372) :1871-1872

[6] The use of fractional polynomials to model continuous risk variables in epidemiology [J].

Royston, P ;

Ambler, G ;

Sauerbrei, W .

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 1999, 28 (05) :964-974

[7] TUBERCULIN REACTIVITY AFTER NEWBORN BCG IMMUNIZATION IN MONOZYGOTIC AND DIZYGOTIC TWINS [J].

SEPULVEDA, RL ;

HEIBA, IM ;

NAVARRETE, C ;

ELSTON, RC ;

GONZALEZ, B ;

SORENSEN, RU .

TUBERCLE AND LUNG DISEASE, 1994, 75 (02) :138-143

[8]

Stearns TM, 2005, J ANIM SCI, V83, P2471

[9] Genome Scan of M-tuberculosis Infection and Disease in Ugandans [J].

Stein, Catherine M. ;

Zalwango, Sarah ;

Malone, LaShaunda L. ;

Won, Sungho ;

Mayanja-Kizza, Harriet ;

Mugerwa, Roy D. ;

Leontiev, Dmitry V. ;

Thompson, Cheryl L. ;

Cartier, Kevin C. ;

Elston, Robert C. ;

Iyengar, Sudha K. ;

Boom, W. Henry ;

Whalen, Christopher C. .

PLOS ONE, 2008, 3 (12)

[10] Evidence for a major gene influence on tumor necrosis factor-α expression in tuberculosis:: Path and segregation analysis [J].

Stein, CM ;

Nshuti, L ;

Chiunda, AB ;

Boom, WH ;

Elston, RC ;

Mugerwa, RD ;

Iyengar, SK ;

Whalen, CC .

HUMAN HEREDITY, 2005, 60 (02) :109-118

← 1 2 →