Messenger RNA expression of IL-8, FOXP3, and IL-12beta differentiates latent tuberculosis infection from disease.
Differentiation of active from latent tuberculosis (TB) is a major challenge in the control of TB. In this study, PBMC from latent TB-infected subjects, TB patients, and tuberculin skin test-negative donors stimulated with the Mycobacterium tuberculosis (Mtb)-specific Ag, early secretory antigenic target 6, and mRNA for 45 immune-related genes was measured by quantitative real-time PCR. Univariate analysis showed significant differences in the expression of 10 genes (IFN-gamma, FOXP3, IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, IL-12alpha, IL-12beta, and IL-24) in PBMC from TB patients vs latent TB-infected subjects (p < 0.01). Multivariate logistic regression and classification and regression tree analyses revealed that expression of three genes, IL-8, FOXP3, and IL-12beta, is predictive for TB vs latent Mtb infection. Thus, measurement of Ag-specific expression of these three genes may offer a specific and noninvasive means of differentiating between latent Mtb infection and TB.
Wu
Bo
B
Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Huang
Chunhong
C
Kato-Maeda
Midori
M
Hopewell
Philip C
PC
Daley
Charles L
CL
Krensky
Alan M
AM
Clayberger
Carol
C
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis* / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012189:Retrospective Studies; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism*
D000942:Antigens, Bacterial; C508606:CXCL8 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D016209:Interleukin-8; D007378:Interleukins