Gene expression and cytokine pattern of pulmonary tuberculosis patients and their contacts in Ethiopia

[摘要] ENGLISH ABSTRACT: The immune response against M. tuberculosis is multifactorial, involving a network of innateand adaptive immune responses. Characterization of the immune response, a clearunderstanding of the dynamics and interplay of different arms of the immune response andthe identification of infection-stage specific biomarkers are critical to allow thedevelopment of better tools for combating tuberculosis. In an attempt to identify suchbiomarkers, we studied pulmonary tuberculosis patients and their contacts in Addis Ababa,Ethiopia as part of EDCTP and BMGF funded tuberculosis projects by using multiplextechniques. We analysed 45 genes using the Multiplex Ligation Dependent ProbeAmplification (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. Singlegenes predict with an area under the Receiver Operating Characteristic (ROC) curve of 0.68to 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 combinationsof plasma cytokines and chemokines discriminate between different clinical groupsaccurately. The median plasma level of EGF, fractalkine, IFN-y, IL-4, MCP-3 and IP-10 issignificantly different (p<0.05) in active tuberculosis and non active tuberculosis infectionand the median plasma levels of IFN-y, IL-4, MCP-3, MIP-1ß and IP-10 were significantlydifferent (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 anddifferent families of the modern lineage. The plasma level of IL-4 was significantly higher inpatients infected with lineage 3 (p<0.05) as compared to lineage 4 and the CAS familyinfectedpatients had a higher plasma level of IL-4 (P<0.05) as compared to patients infectedwith 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 differentsettings and we believe that these molecules are very promising biomarkers for classifyingactive tuberculosis, latent infection, absence of infection and treated infection. Thesemarkers may be suitable for the development of clinically useful tools but require furthervalidation and qualification in different populations and in larger studies.

[发布机构] Stellenbosch University