The Role of a Mycobacterium Growth Inhibition Assay to Quantify Host Immune Control of M. Tuberculosis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: No intervention..
- Who it may be relevant to
- Registry conditions: Tuberculosis, Immunologic Activity Alteration. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Sweden
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
The Role of a Mycobacterium Growth Inhibition Assay to Quantify Host Immune Control of M. Tuberculosis From Healthy Blood Donors and Patients With Latent or Active Tuberculosis.
Overview
The goal of this observational study is to learn about how the blood leucocytes from patients with and without exposure or disease from tuberculosis (TB) are able to kill live mycobacteria (M. tuberculosis). The main question it aims to answer is: Is intracellular growth suppression of M. tuberculosis in peripheral blood mononuclear cells variable among healthy blood donors and higher than in patients with latent TB compared to active TB?
Detailed description
Background: The host immune response is crucial in determining the outcome after exposure to Mtb. A substantial proportion of exposed individuals (40-70%) never develop infection indicating an efficient cell mediated immune response against Mtb and early clearance by the host immune defense (Verall et al, Immunology 2014). Thus, the outcome of exposure is highly dependent on host immunity. In this study, our aim was to investigate whether the previously developed mycobacterium groth inhibition assay (MGIA) method (Andersson et al, Tuberculosis 2020) could be used to quantify the host immune response to Mtb.
Study design: In this study we will include healthy donors (n=80), patient with active TB (n=40), subjects recently exposed to active TB (n=80) and patients with latent TB (LTBI) (n=80). Exclusion criteria for all groups are known HIV infection or other immunosuppression from treatment or disease. Patients and healthy blood donors will be recruited at the departments of infectious diseases in Region Kalmar and Region Östergötland. From patients giving oral and written consent, 40 ml of blood will be collected for MGIA analysis.
Primary aim: To determine the difference in MGIA between healthy blood donors and patients with latent and active TB as well as the variation in host control of Mtb within each group.
Method: The Mycobacterial growth inhibition assay (MGIA) using human PBMCs isolated by density gradient by Lymhoprep (Axis-Shield) and SepMate tubes (StemCell Technologies) will be performed as described in study I with minor modifications. The PBMCs are infected with GFP expressing M. tuberculosis H37Rv and intracellular growth of Mtb and viability of PBMCs are assessed by live-cell imaging (Incucyte©) and measured as relative fluorescence units (RFU) during 5 days with and without stimulation with the purified protein derivate (PPD) is included. The cytokine response following exposure to gamma-irradiated H37Rv will be quantified by Olink proteomics.
Interventions
- Other No intervention.
Blood sampling for analysis of mycobacterial growth inhibition assay (MGIA) analysis.
Primary outcome measures
- Mycobacterial inhibition of host macrophages [Time frame: Up to 10 days incubation]
- Mycobacterial inhibition of host peripheral blood mononuclear cells (PBMCs) [Time frame: Up to 10 days incubation]
Secondary outcome measures (1)
- Cytokine expression of host peripheral blood mononuclear cells (PBMCs) [Time frame: 24 hours]
Eligibility criteria
Inclusion Criteria: Healthy blood donors or subjects who will get vaccinated.
Exclusion Criteria:Known HIV infection, not Swedish citizen, chronic liver och kidney disease,immunosuppression from treatment or disease.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
Sweden · 2 centers
- Kalmar County Hospital — Kalmar
- Dept of Infectious Diseases — Linköping
Identifiers
NCT: NCT06580639 · 2022-06858-02