Search and validation of biomarkers for tuberculosis in Mexican patients with diabetes mellitus

Background

Today, the traditional test in the health sector to assume an infection by Mycobacterium tuberculosis in asymptomatic people is based on delayed hypersensitivity immune response to a complex mixture of antigens derived from the purified protein derivative (PPD) or tuberculin, whose most abundant constituents are shared by other mycobacteria, resulting in sensitivity and specificity values of around 80%. As a solution to this lack of ability to detect at least 20% of cases based on ex vivo cell response to particular antigens of M. tuberculosis, some commercial kits were generated. Despite the progress that these methods represent, their demonstrated usefulness is not entirely satisfactory when used in various populations. Thanks to this, and taking advantage of the possibility of conducting a screening for all proteins encoded in the genome of M. tuberculosis within a chip/ protein microarray, we propose the search and validation of biomarkers for tuberculosis, specifically in Mexican patients with diabetes mellitus.

Aims

Develop a diagnostic method based on a panel of mycobacterial antigenic proteins, to detect asymptomatic tuberculosis in Mexican patients with diabetes mellitus, with sensitivity and specificity greater than or equal to 80%, from antigens present in the complete proteome of M. tuberculosis.

Project plan

1. Determine the ability to detect antigenic proteins from the complete proteome of M. tuberculosis, produced in a microarray, using antibodies present in sera from healthy subjects, patients with active tuberculosis, diabetes mellitus patients with negative PPD reactivity, and patients with diabetes mellitus and positive PPD reactivity.

2. Once identified the antigenic proteins, verify the sensitivity and specificity of detection of antigenic proteins individually, to find candidate biomarkers, and validate their recognition by sera from healthy subjects, patients with active tuberculosis, diabetes mellitus patients with negative PPD reactivity, and patients with diabetes mellitus and positive PPD reactivity.

3. Validate the cross-reactivity of candidate biomarkers in study groups and cases of diabetic patients with other infectious diseases.

Impact

Tuberculosis is harder to identify in patients with Type 2 Diabetes and this has an ongoing impact on patient management. Evidence from the project suggests that improved testing for TB in patients with Type 2 Diabetes would lead to better management of people with both conditions.

Principal investigators

Team members

Funding organisations

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