MicroRNAs are biomarkers of post primary tuberculosis.
Shepelkova G.S., Evstifeev V.V., Ergeshova A.E., Tarasov R.V., Bagirov M.A., Yeremeev V.V.
Central Tuberculosis Research Institute, Moscow, Russian Federation

A precondition for the development of post primary tuberculosis (TB) is the fault of natural resistance and specific immunity. Lung tuberculoma is a clinical form of TB, combining various encapsulated caseous foci with a long and often low-symptom course. Tuberculomas can have different genesis and originate from focal, infiltrative or dissiminated TB.
Fibrouscavernous pulmonary TB (FCT) is a chronic form characterized by the presence of a fibrous cavity, the development of fibrotic changes in the lung tissue and foci of bronchogenic dropout. FCT can result from the progression of any other form of pulmonary TB.
For the early initiation of adequate chemotherapy of TB, rapid differential diagnosis of the latent and active stages of the disease is important. MicroRNAs (miRs) might play a major part in the outcome of TB, since early work has implicated miRs as regulators of the immune response.
Aim: In this study we describe serum expression pattern of 5 selected miRs in patients with different variants of post primary TB. We analyzed their value as biomarkers of inflammation activity in TB patients.
Methods: Serum samples were collected from 30 patients with FCT, 30 patients with “silent” tuberculoma, 30 patients – tuberculoma with “decay” and 30 TB contacts. RNA was extracted with TRIzol LS. 3 pools of extracted RNA within each group were analyzed by miScript miRNA PCR Array (QIAGEN) to select the users miRNAs set and TaqMan RT-PCR Assay was used for data verification.
Results: The analysis by miRNA PCR Array displayed differences in the expression of the miRs in TB patients as compared with the control group, and between the three groups of patients with different forms of TB. Data verification using real-time PCR displayed significant differences in the miRs profile of FCT patients compared with the contact group. The most prominent results were identified in patients with FCT: serum expression of miR-222, miR-223, miR-191 was downregulated, and expression of miR-26a was upregulated. The expression profile of serum miRNAs in tuberculoma with decay patients resembled that of FCT group. In “silent” tuberculoma group miR-191 expression was upregulated and miR-155 expression was inhibited.
Conclusions: We demonstrated significant changes of miRs levels in patients with various forms of post primary TB. These changes involved miRs from inflammatory and the fibrotic pathways. Our data form the basis for the development of a set of biomarkers for post primary TB variants.
This work was supported by the Scientific Program SR 0515-2019-0018.

Galina S. Shepelkova PhD

Central Tuberculosis Research Institute, Moscow, RF

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