Department of Biomedical Sciences

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Browsing Department of Biomedical Sciences by browse.metadata.advisor "Aseffa, Abraham"

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    Gene expression and cytokine pattern of pulmonary tuberculosis patients and their contacts in Ethiopia
    (Stellenbosch : Stellenbosch University, 2013-03) Bekele, Adane Mihret; Walzl, Gerhard; Howe, Rawleigh; Aseffa, Abraham; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division Molecular Biology and Human Genetics.
    ENGLISH ABSTRACT: The immune response against M. tuberculosis is multifactorial, involving a network of innate and adaptive immune responses. Characterization of the immune response, a clear understanding of the dynamics and interplay of different arms of the immune response and the identification of infection-stage specific biomarkers are critical to allow the development of better tools for combating tuberculosis. In an attempt to identify such biomarkers, we studied pulmonary tuberculosis patients and their contacts in Addis Ababa, Ethiopia as part of EDCTP and BMGF funded tuberculosis projects by using multiplex techniques. We analysed 45 genes using the Multiplex Ligation Dependent Probe Amplification (MLPA) technique and the expression of IL-4δ2, BLR1, MARCO, CCL-19, IL7R, Bcl2, FcyR1A, MMP9, and LTF genes discriminate TB cases from their healthy contacts. FoxP3, TGFß1 and CCL-19 discriminate latently infected from uninfected contacts. Single genes predict with an area under the Receiver Operating Characteristic (ROC) curve of 0.68 to 0.85 while a combination of genes identified up to 95% of the different groups. Similarly, the multiplex analysis of cytokines and chemokines also showed that single or combinations of plasma cytokines and chemokines discriminate between different clinical groups accurately. The median plasma level of EGF, fractalkine, IFN-y, IL-4, MCP-3 and IP-10 is significantly different (p<0.05) in active tuberculosis and non active tuberculosis infection and the median plasma levels of IFN-y, IL-4, MCP-3, MIP-1ß and IP-10 were significantly different (p<0.05) before and after treatment. We also found a significant difference (p<0.05) in plasma levels of cytokines of patients infected with the different lineages and different families of the modern lineage. The plasma level of IL-4 was significantly higher in patients infected with lineage 3 (p<0.05) as compared to lineage 4 and the CAS familyinfected patients had a higher plasma level of IL-4 (P<0.05) as compared to patients infected with H and T families but there was no difference between H and T families. We identified genes and cytokines which had been reported from other studies in different settings and we believe that these molecules are very promising biomarkers for classifying active tuberculosis, latent infection, absence of infection and treated infection. These markers may be suitable for the development of clinically useful tools but require further validation and qualification in different populations and in larger studies.