Leiden University Scholarly Publications

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Sahiratmadja, E.K. (2007)

Innate and adaptive host responses and their genetic control in tuberculosis : studies in Indonesia, a highly TB endemic setting

Doctoral Thesis
Tuberculosis (TB) is an infectious disease, caused by Mycobacterium tuberculosis. MTB infection does not necessarily progress to TB. Only 5-10% of exposed individuals develop clinical signs and symptoms of TB. Given the impact of mycobacterial exposure and the immunoregulatory consequences for host immunity, it is important to study the integrity and the regulation of immune responses and their downstream signaling pathways in TB endemic areas. Indonesia is a highly TB-burdened country and ranks third globally in TB cases. This thesis, consisting of six studies, explored variation in host immune responses to TB and their genetic background, and variation in clinical presentation. (1) MTB-specific stimulation of IFN-_ production as well as IFN-_ receptor signaling was significantly down-regulated during active TB, correlated with disease severity and __activity. (2) Concentrations of plasma granulysin of active TB patients were found to be low during acute disease. (3) Several...Show moreTuberculosis (TB) is an infectious disease, caused by Mycobacterium tuberculosis. MTB infection does not necessarily progress to TB. Only 5-10% of exposed individuals develop clinical signs and symptoms of TB. Given the impact of mycobacterial exposure and the immunoregulatory consequences for host immunity, it is important to study the integrity and the regulation of immune responses and their downstream signaling pathways in TB endemic areas. Indonesia is a highly TB-burdened country and ranks third globally in TB cases. This thesis, consisting of six studies, explored variation in host immune responses to TB and their genetic background, and variation in clinical presentation. (1) MTB-specific stimulation of IFN-_ production as well as IFN-_ receptor signaling was significantly down-regulated during active TB, correlated with disease severity and __activity. (2) Concentrations of plasma granulysin of active TB patients were found to be low during acute disease. (3) Several genetic markers have been identified to affect susceptibility to TB (IL12B, IL12RB1, IFNG and IFNGR1) and (4) TLR8, DC-SIGN, complement component and scavenger receptor. (5) NRAMP polymorphisms were, however, not associated with susceptibility to TB. (6) TB with concomitant type2 DM presented more symptoms; screening fasting blood glucose in TB patients is clinically important.Show less
Tuberculosis
Mycobacterium tuberculosis
Indonesia
Cytokine
IFN gamma
TNF
Granulysin
Polymorphisms
Diabetes Mellitus type 2
All authors
Sahiratmadja, E.K.
Supervisor
Ottenhoff, T.H.M.
Co-supervisor
Vosse, E. van de
Qualification
Doctor (dr.)
Awarding Institution
Department of Infectious Diseases/ Department of ImmunoHematology and Bloodtransfusion, Leiden University Medical Center (LUMC), Leiden University
Date
2007-11-27
ISBN (print)
9789081205511

Juridical information

Court
LEI Universiteit Leiden