Plasma Immune Biomarkers Predictive of Progression to Active Tuberculosis in Household Contacts of Patients With Tuberculosis

Author:

Rajamanickam Anuradha1ORCID,Ann Daniel Evangeline23,Dasan Bindu1,Thiruvengadam Kannan2,Chandrasekaran Padmapriyadarsini2,Gaikwad Sanjay4,Pattabiraman Sathyamurthi2,Bhanu Brindha2,Sivaprakasam Amsaveni2,Kulkarni Vandana56,Karyakarte Rajesh7,Paradkar Mandar56,Shivakumar Shri Vijay Bala Yogendra6,Mave Vidya568ORCID,Gupta Amita8ORCID,Hanna Luke Elizabeth2,Babu Subash19

Affiliation:

1. National Institute of Health-National Institute of Allergy and Infectious Diseases–International Center for Excellence in Research , Chennai , India

2. ICMR-National Institute for Research in Tuberculosis, Indian Council of Medical Research , Chennai , India

3. University of Madras , Chennai , India

4. Department of Pulmonary Medicine, Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals , Pune , India

5. Byramjee Jeejeebhoy Government Medical College–Johns Hopkins Clinical Research Site , Pune , India

6. Johns Hopkins Center for Infectious Diseases in India , Pune , India

7. Department of Microbiology, Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals , Pune , India

8. Division of Infectious Diseases, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA

9. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA

Abstract

Abstract Background The progression from Mycobacterium tuberculosis infection to active tuberculosis disease varies among individuals, and identifying biomarkers to predict progression is crucial for guiding interventions. In this study, we aimed to determine plasma immune biomarker profiles in healthy household contacts of index patients with pulmonary tuberculosis, who either progressed to tuberculosis or remained as nonprogressors. Methods A cohort of household contacts of adults with pulmonary tuberculosis was enrolled, consisting of 15 contacts who progressed to tuberculosis disease and 15 nonprogressors. Plasma samples were collected at baseline, 4 months, and 12 months to identify predictive tuberculosis progression markers. Results Our findings revealed that individuals in the progressor group exhibited significantly decreased levels of interferon (IFN) γ, tumor necrosis factor α, interleukin 2, IL-1α, IL-1β, and 17A, and interleukin 1 receptor antagonist (IL-1Ra) at baseline, month 4, and month 12. In contrast, the progressor group displayed significantly elevated levels of IFN-α, IFN-β, interleukin 6 and 12, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10) and 33 (IL-33), CCL2, CCL11, CXCL8, CXCL10, CX3CL1, vascular endothelial growth factor, granzyme B, and programmed death ligand -1 compared to the nonprogressor group at baseline, months 4 and 12. Receiver operating characteristic analysis (ROC) identified IFN-γ, GM-CSF, IL-1Ra, CCL2, and CXCL10 as the most promising predictive markers, with an area under the receiver operating characteristic curve of ≥90. Furthermore, combinatorial analysis demonstrated that GM-CSF, CXCL10, and IL-1Ra, when used in combination, exhibited high accuracy in predicting progression to active tuberculosis disease. Conclusions Our study suggests that a specific set of plasma biomarkers, GM-CSF, CXCL10, and IL-1Ra, can effectively identify household contacts at significant risk of developing tuberculosis disease. These findings have important implications for early intervention and preventive strategies in tuberculosis-endemic regions.

Funder

Government of India's

Department of Biotechnology

Indian Council of Medical Research

Office of AIDS Research

Division of Intramural Research

(support to S. B.)

National Institute of Allergy and Infectious Diseases

National Institutes of Health

CRDF Global

Publisher

Oxford University Press (OUP)

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