Tb Infection State Of Host On The Difference Of N/med Tuberculosis Specific Antigen Acquired Immune Response And Related Molecular Identity Screening

Tuberculosis (TB) is a chronic disease caused by mycobacterium tuberculosis (MTB) and exhibits as respiratory infections in most cases. In recent years, the TB epidemic becomes more and more serious, and it is considered as the most notorious infectious disease that is resulted from single pathogen. Now,1/3of the worldwide populations are infected by MTB, in which about9.3million people will become the active tuberculosis and more than1.8million people will die. Latent infectious patients bring about severe challenge to the diagnosis and control of TB. However, little is known about the key immune mechanisms involved how to prevent the latent infectious status from becoming to be the active condition. Accordingly, clarifying the immune response differences in active and latent infectious TB comprehensively is very important for uncovering the mystery of the anti-infection immunity mechanisms. Furthermore, finding new specific biomarkers to recognize active TB and TB infection will also make great contribution to the control of TB.One of the goals of this study is to investigate the immune response differences in individuals with different MTB infectious status, using whole genome microarray. We selected four patients with active tuberculosis (TB),4latent TB infectious individuals (LTBI) and four non-infected healthy controls (HC), isolated their PBMCs and stimulated PBMCs with MTB-specific antigen PPD for4hours. Statistical analysis of microarray data showed that the immune response of PBMCs from TB group is most different from that of LTBI group when challenged by PPD, with286differentially expressed genes. The number of differentially expressed genes between TB and HC is239. LTBI group and HC group showed the smallest difference with94differentially expressed genes. Finally, we get506differentially expressed genes in the pair-wise comparisons in these three groups.Next, we focused our analyses on identifying unique gene expression profiles of tuberculosis infection and active disease. We compared (1) TB and LTBI groups with HC group to determine the genuine transcriptional signature of TB infection regardless of disease or not, and (2) TB group with LTBI and HC groups to discover the gene expression signature of active disease regardless of infection or not, when stimulated with PPD. Finally,55and229-gene-profiles were identified, which might be considered as being uniquely associated with tuberculosis infection (TB and LTBI) and active disease (TB), respectively.In order to validate the microarray results, we recruited another83individuals, including25TB patients,36LTBI individuals and22healthy controls. As high as81%qPCR results were confirmed to display the same patterns as the microarray study.Basing on the differently expressed genes in qPCR, we try to screen new biomarkers about TB patients and TB infection. ROC methodology and decision tree analysis showed that the combination of gene expression levels of CXCL10, ATP10A and TLR6was endowed with the best predictive capacity between TB and LTBI. The sensitivity and specificity is80%and89%, respectively. In addition, the combination of CXCL10, RAB20and IL2can discriminate TB from LTBI and HC, with72%sensitivity and97%specificity. In the discrimination between TB infection and HC, the combination of IFN-γ, CXCL10, CXCL9and IL2RA performed well with98%sensitivity and59%specificity.