The role of immunogenetic factors and vitamin D deficiency in tuberculosis

RID-TB

About this project

Hypothesis

Tuberculosis (TB) persists as one of the most significant causes of morbidity and mortality among infectious diseases worldwide, with the latest World Health Organization figures indicating 1.6 million TB-associated deaths in 2021. 1 It remains crucial to elaborate specific interventions with the aim of preventing infection initiation, and the progression from latent TB infection (TBLI) to active TB. One possibility of identifying a tailored disease path has laid in the connection between vitamin D deficiency and an increased risk of unfavourable outcomes derived from the contact with Mycobacterium tuberculosis, through altered autophagy and an inadequate cytokine response to it.
The RID-TB project (2015-2017), through its overall objective, consisted in the study of a possible correlation between underlying mechanisms associated with inadequate levels of vitamin D (genetic polymorphisms and vitamin D-dependent immune signalling pathways) and the risk of LTBI and active TB, in a cohort of Romanian patients.

Objectives

1. Measuring Vitamin D and parathyroid hormone (PTH) for all the cohort subcategories (active TB, LTBI and healthy controls);
2. Identifying genetic susceptibility related to the vitamin D receptor and the vitamin D-dependent immune signaling pathways;
3. Evaluating cytokine response in relation to vitamin D levels and the individual genetic landscape;
4. Creating a model estimating  disease risk, based on the plasma vitamin D levels and genotype correlation;
Establishing a biobank for sample storage, with the aim of further study.

The techniques employed in the study included RT-PCR genotyping, ex-vivo stimulation experiments

From a public health perspective, this project aimed for an immediate, positive impact for the community it was implemented in. Its basis followed modelling studies, which suggested that improving case detection rates could be the only measure for better TB management in Romania, offering important data on the prevalence and distribution of TB and TBL among household contacts in a TB-endemic region. RID-TB included 110 TB patients and 251 household contacts of the patients, enrolled from “Victor Babes” Infectious Disease Hospital.

The results so far derived from the RID-TB project included the investigation of ATG5 and NOD2 polymorphisms in relation to an altered autophagy function in TB patients, and that of the CARD9 gene polymorphisms. 2, 3

1.        Global tuberculosis report 2022. https://www.who.int/publications-detail-redirect/9789240061729.
2.        Streata, I. et al. The CARD9 Polymorphisms rs4077515, rs10870077 and rs10781499 Are Uncoupled from Susceptibility to and Severity of Pulmonary Tuberculosis. PLOS ONE 11, e0163662 (2016).
3.        Cucu, M. G. et al. Polymorphisms in autophagy genes and active pulmonary tuberculosis susceptibility in Romania. Rev. Romana Med. Lab. 25, 47–53 (2017).

Teams

Our research team at the Medical Genetics Department of UMF Cluj-Napoca studies the mechanisms of inflammatory diseases and their interrelationship with individual genetic susceptibility factors. We are curious how the variance in our genome or epigenome can alter the immunological processes and cause inflammatory disease. We assess immunological functions of primary cells in patient cohorts and in controls and we use multi-omics to assess the different molecular layers that can contribute to inflammatory dysregulation. Currently, we are investigating the mechanisms of immune memory associated to long term proinflammatory effects and accelerated immunological aging in gout, hyperuricemia, systemic sclerosis and other autoinflammatory and autoimmune disorders.

Craiova Human genomics

Cluj Functional Genomics

Cluj Medical Genetics

Cluj Rheumatology

Cluj Infectious Diseases

Stay Informed

Follow us on our social media

Get access to groundbreaking research, events, and scientific insights from the HFGP Romania.

Scroll to Top