DNA hyper-methylation during Tuberculosis dampens host immune responsiveness

DNA Methylation was analyzed in tuberculosis patients without HIV at baseline and 6 months after completion of successful therapy. DNA methylation was also evaluated in TB patients with HIV and in healthy controls without Tuberculosis. 500ng of gDNA was bisulfite treated prior to running the Illumina Infinium MethylEPIC array The study protocol was reviewed by the Baylor College of Medicine Children’s Foundation-Swaziland, Baylor College of Medicine and Eswatini National Health Research and Review Board. All participation was voluntary and implemented in accord with the institutional and international guidelines for the Protection of Human Subjects in concordance with the Declaration of Helsinki including written informed consent from participants or their guardians. In this analysis, immune cells of TB participants were analyzed if they had pulmonary disease as defined by symptoms of TB (cough, fevers, weight loss, etc) and microbiologically confirmed disease by sputum Gene Xpert and/ or culture. All participants were screened for HIV. Healthy controls were household contacts of TB patients with a TB contact score of five or greater and excluded if they progressed to active TB and did not remain asymptomatic for 12- months. All individuals were BCG vaccinated as confirmed by BCG scar and/ or vaccine card.