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Evaluation of MIR-29a, MIR-144, MIR-146A and MIR-155 with il-6, TNF-α, IFN-γ, IL-17 and il1-β as A predictive marker for early diagnosis and prognosis of active pulmonary tuberculosis

2020
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Advisor: Prof. Dr. Fatih Köksal

Abstract (EN)

Tuberculosis (TB) is one of the oldest diseases known to the mankind; remains a major cause of mortality worldwide. Estimates that approximately quarter of the population of the world is infected with Mycobacterium tuberculosis and that more than 10 million new cases of active TB occur and mortality from TB is close to 1 million people annually. Host immun system such as environmental and genetic factor and, host- pathogen interactions play an important role in the risk of developing active tuberculosis. Currently, the molecular pathogenesis and immunopathological events of tuberculosis are still unclear, but host immune system plays a major role in protective immunity aganist tuberculosis and this process includes many components of the immune system. Animal and human studies have established that micrornas and cytokines have a crucial role in mycobacterial infectıons and the course of infection. MicroRNAs (miRNAs), are known to have significant roles in many biological process including cell differentiation, development, apoptosis and immun response and evidence have been demostrated that microRNAs are associated with mainly cancer and infectious diseases with morbidity and mortality such as tuberculosis. Cytokines are also small protein molecules that regulate immunological responses at cellular level, recruit wide range of cells involved in immunity and inflammation. The development of predictive diagnostic methods is essential for tuberculosis control and assesment of treatment outcome. MicroRNAs and cytokines are promising bioindicators as a ideal potential biomarker and terapotic agent for early detection of active TB and prognosis of treatment. In this study 50 patients with microbiogically proven tubeculosis who did not receive anti-tuberculosis therapy and 50 healthy volunteers were enrolled. plasma obtained from blood samples which taken from each patients and control group and miR-29a miR-144, miR-155, miR146-a that are known to regulate immune responses by modulating gene expression of immune-related genes were evaluated by high capacity Real-Time PCR device. . Expression leves of IL-6, TNF-α, IFN-γ, IL-17, IL1-β which are known to play a protective immunity against tuberculosis were measured by enzyme linked-immunosorbent assay (ELİSA). At the same time, sensitivity and specificity values of the obtained results were determined by Receveir Operating Curve (ROC) Analysis. When stratified into the patient and control group showed a statistically significant association with expressions of the plasma miR-146a, miR-29a and miR-144, level of TNF-α, IFN-γ, IL-17, IL1-β were present. (p<0.005) The ROC analysis identified that mir-29a, miR-144 and miR-146a have good discriminatory power between two groups. There were no statistically significant correlation between microRNAs and cytokines. In conclusion; The change in plasma microRNA and cytokine levels of patients with active pulmonary tuberculosis compared with the control group, especially the correlation between microRNA levels and cytokine secretion levels are important as a diagnostic biomarker in the diagnosis and prognosis of active tuberculosis and ıt was concluded that these host biomarkers will contribute to wider surveillance studies to better understand the role of immunopathogenesis of TB.

Author

Fırat Karslı

How to Cite

Fırat Karslı (Doctorate thesis). Evaluation of MIR-29a, MIR-144, MIR-146A and MIR-155 with il-6, TNF-α, IFN-γ, IL-17 and il1-β as A predictive marker for early diagnosis and prognosis of active pulmonary tuberculosis, 2020, Çukurova University.

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