biomarker changes associated with tuberculin skin test (tst) conversion a two-year longitudinal follow-up study in exposed household contacts生物标志物的变化与结核菌素皮肤试验(tst)转换一个为期两年的纵向随访研究中暴露的家庭接触者.pdf

Biomarker Changes Associated with Tuberculin Skin Test (TST) Conversion: A Two-Year Longitudinal Follow-Up Study in Exposed Household Contacts 1 1 1 2 Rabia Hussain *, Najeeha Talat , Firdaus Shahid , Ghaffar Dawood 1 Department of Pathology and Microbiology, The Aga Khan University, Karachi, Pakistan, 2 Masoomeen General Hospital, Kharadar, Karachi, Pakistan Abstract Background: A high prevalence (50–80%) of Tuberculin Skin Test Positivity (TST+ $10 mm indurations) has been reported in TB endemic countries. This pool forms a huge reservoir for new incident TB cases. However, immune biomarkers associated with TST conversion are largely unknown. The objective of this study was to identify immune biomarkers associated with TST conversion after acute Mycobacterium tuberculosis (MTB) exposure. Methodology/Principal Findings: A 24 month longitudinal study was carried out in a recently MTB exposed cohort of household contacts (HC = 93; 75% TST+). Control group consisted of unexposed community controls (EC = 59; 46%TST+). Cytokine secretion was assessed in whole blood cultures in response to either mycobacterial culture filtrate (CF) antigens or mitogens (PHA or LPS) using Elisa methodology. Compared to the EC group, the HC group at recruitment (Kruskal-Wallis Test) showed significantly suppressed IFN c (p = 0.0001), raised IL-10 (p = 0.0005) and raised TNF a (p = 0.001) in response to CF irrespective of their TST status. Seventeen TST-HC, showed TST conversion when retested at 6 months. Post TST conversion (paired t tests) significant increases were observed for CF induced IFN c (p = 0.038), IL-10 (p = 0.001) and IL-6 (p = 0.006). Cytokine responses were also compared in the exposed HC group with either recent infection [(T