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Sponsored by: |
Chang Gung Memorial Hospital |
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Information provided by: | Chang Gung Memorial Hospital |
ClinicalTrials.gov Identifier: | NCT00772408 |
Infection with Mycobacterium tuberculosis remains at epidemic levels globally. Innate and adaptive immune responses evolve as protective mechanisms against mycobacterial infection in humans. Toll-like receptors (TLRs) are transmembrane proteins characterized by an extracellular leucine-rich domain that participates in ligand recognition and an intracellular tail. TLRs are the first defense system to detect potential pathogens, initiate immune responses and form the crucial link between innate and adaptive immune systems. Stimulation of TLR initiates a signaling cascade that involves a number of proteins, such as MyD88 and IL-1 receptor-associated kinase. This signal cascade leads to NF-κB activation, which induce the secretion of pro-inflammatory cytokines.
TLR2 is a family of TLR family and has been reported to be the principle mediator of macrophage activation in response to mycobacterium. Growing amounts of data suggest that the ability of certain individuals to respond properly to TLR ligands may be impaired by single nucleotide polymorphisms (SNPs) within TLR genes, resulting in an altered susceptibility to, or course of, infectious disease. The genetic polymorphism of TLR2 (arginine to glutamine substitution at residue 753 (Arg753Gln)) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to mycobacteria. In addition, another polymorphism (Arg677Trp) of the TLR2 was reported to be associated with susceptibility to tuberculosis in Tunisian patients. Moreover, in Mycobacterium leprosy patients with TLR2 mutation (Arg677Trp), production of IL-2, IL-12, IFN-gamma, and TNF-alpha by M. leprae-stimulated peripheral blood mononuclear cell were decreased compared with that in groups with wild-type TLR2.
To date, there have been no studies of the association of SNPs of TLR2 with cytokine profiles and clinical outcomes on M. tuberculosis. We hypothesize that polymorphisms in the TLR2 are associated with :
Condition |
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Pulmonary Tuberculosis Genetic Variants of Host Immune Response of Host |
Study Type: | Observational |
Study Design: | Case Control, Prospective |
peripheral blood leukocyte DNA and plasma
Estimated Enrollment: | 350 |
Study Start Date: | August 2006 |
Estimated Study Completion Date: | November 2008 |
Groups/Cohorts |
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TB
patients with pulmonary TB
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control
healthy controls
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Ages Eligible for Study: | 20 Years to 90 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Probability Sample |
Case: patients visiting the Pulmonary department of Chang Gung Memorial Hospital, Kaohsiung, Taiwan Control:healthy subjects visiting the Center of health examination at Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Inclusion Criteria:
a) findings on CXR that are compatible with presentations of Mycobacterium tuberculosis b) clinical symptoms, such as fever, body weight loss, night sweating, chest pain and chronic cough, that indicate active infection of pulmonary tuberculosis (TB) c) microbiological diagnosis by sputum smear and culture, bronchoalveolar lavage fluid culture, or DNA probe examination.
d) Resolution on CXR with anti-TB regimens e) Written informed consent form prior to participation into this study
Exclusion Criteria:
Contact: Yung-Che Chen, MD | 886-7-7317123 ext 8199 | yungchechen@yahoo.com.tw |
Taiwan | |
Kaohsiung Chang Gung Memorial Hospital | Recruiting |
Kaohsiung, Taiwan, 886 | |
Contact: Meng-Chih Lin, MD 886-7-7317123 ext 8300 mengchih@adm.cgmh.org.tw | |
Principal Investigator: Yung-Che Chen, MD | |
Kaohsiung Chang Gung Memorial Hospital | Recruiting |
Kaohsiung Hsien, Taiwan, 886 | |
Contact: Meng-Chih Lin, MD 886-7-7317123 ext 8300 mengchih@adm.cgmh.org.tw |
Principal Investigator: | Meng-Chih Lin, MD | Kaohsiung Chang Gung Memorial Hospital |
Responsible Party: | Chang Gung Memorial Hospital, Kaohsiung ( Meng-Chih Lin ) |
Study ID Numbers: | NSC 95-2314-B-182A-030 |
Study First Received: | October 13, 2008 |
Last Updated: | October 13, 2008 |
ClinicalTrials.gov Identifier: | NCT00772408 |
Health Authority: | Taiwan: Institutional Review Board |
pulmonary tuberculosis Toll-like receptor 2 gene polymorphisms blood lymphocyte subsets systemic symptoms pleural effusion |
Bacterial Infections Pleural Effusion Gram-Positive Bacterial Infections Respiratory Tract Infections Respiratory Tract Diseases Disease Susceptibility |
Tuberculosis, pulmonary Lung Diseases Tuberculosis, Pulmonary Mycobacterium Infections Tuberculosis Genetic Predisposition to Disease |
Actinomycetales Infections |