Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk
Kamakshi Prudhula Devalraju, Deepak Tripathi, Venkata Sanjeev Kumar Neela, Padmaja Paidipally, Rajesh Kumar Radhakrishnan, Karan P. Singh, Mohammad Soheb Ansari, Martin Jaeger, Romana T. Netea-Maier, Mihai G. Netea, Sunmi Park, Sheue-yann Cheng, Vijaya Lakshmi Valluri, Ramakrishna Vankayalapati
Kamakshi Prudhula Devalraju, Deepak Tripathi, Venkata Sanjeev Kumar Neela, Padmaja Paidipally, Rajesh Kumar Radhakrishnan, Karan P. Singh, Mohammad Soheb Ansari, Martin Jaeger, Romana T. Netea-Maier, Mihai G. Netea, Sunmi Park, Sheue-yann Cheng, Vijaya Lakshmi Valluri, Ramakrishna Vankayalapati
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Research Article Immunology Pulmonology

Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk

Abstract

In the current study, we followed 839 household contacts (HHCs) of tuberculosis (TB) patients for 2 years and identified the factors that enhanced the development of TB. Fourteen of the 17 HHCs who progressed to TB were in the 15- to 30-year-old age group. At baseline (the “0“ time point, when all the individuals were healthy), the concentration of the thyroid hormone thyroxine (T4) was lower, and there were increased numbers of Tregs in PBMCs of TB progressors. At baseline, PBMCs from TB progressors stimulated with early secretory antigenic target 6 (ESAT-6) and 10 kDa culture filtrate antigen (CFP-10) produced less IL-1α. Thyroid hormones inhibited Mycobacterium tuberculosis (Mtb) growth in macrophages in an IL-1α–dependent manner. Mtb-infected Thra1PV/+ (mutant thyroid hormone receptor) mice had increased mortality and reduced IL-1α production. Our findings suggest that young HHCs who exhibit decreased production of thyroid hormones are at high risk of developing active TB disease.

Authors

Kamakshi Prudhula Devalraju, Deepak Tripathi, Venkata Sanjeev Kumar Neela, Padmaja Paidipally, Rajesh Kumar Radhakrishnan, Karan P. Singh, Mohammad Soheb Ansari, Martin Jaeger, Romana T. Netea-Maier, Mihai G. Netea, Sunmi Park, Sheue-yann Cheng, Vijaya Lakshmi Valluri, Ramakrishna Vankayalapati

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Figure 4

Hormone levels in the serum of HHCs of TB patients.

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Hormone levels in the serum of HHCs of TB patients. Serum (A) T3 and (B)...
Serum (A) T3 and (B) T4 hormone levels of the nonprogressors (n = 67) and progressors (n = 12) at baseline and follow-up (at TB activation) were quantified by ELISA. All the age-matched nonprogressors were healthy, nonsmoking, and nonalcoholic and were without any immunosuppressive conditions at baseline or at follow-up. Data from smoking and alcoholic progressors were not included. P values were derived using an unpaired, 2-tailed, independent t test. Mean ± SD and P values are shown. (C) The receiver operating characteristic (ROC) curve for the hormone T4; plot shows the ROC curve for T4 hormone levels in nonprogressors (n = 67) and TB progressors (n = 12) at baseline. The ROC curve shows the true-positive rate (sensitivity) and false-positive rate (1-specificity) of the model prediction. The biomarker analysis program in MetaboAnalyst software was used to generate the ROC curves and calculate the AUC.