{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:59:49Z","timestamp":1785427189696,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004532","name":"Japan International Cooperation Agency","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004532","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/022es3t03","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"ICMR","doi-asserted-by":"crossref","award":["HIV\/50213\/09\/2020\/ECD-II"],"award-info":[{"award-number":["HIV\/50213\/09\/2020\/ECD-II"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human immunodeficiency virus and tuberculosis (HIV\/TB) coinfection remains a major global health challenge. Immune dysregulation in HIV complicates TB diagnosis. The type of immune response mounted in tuberculosis is a key determinant in deciding the outcome of the infection. Hence, estimating immune markers is critical for developing diagnostic, monitoring and treatment approaches. A study was conducted to evaluate the diagnostic potential of host-based biomarkers in individuals with HIV\/TB coinfection in comparison to HIV monoinfection receiving antiretroviral therapy. Host-based biomarkers were quantified using commercially available kits. Receiver operated curve (ROC) analysis was conducted to determine diagnostic performance. Routine investigations showed significantly raised ratios of neutrophils, monocytes, and platelets-to-lymphocytes and alkaline phosphatase levels in HIV\/TB coinfection (AUC values &gt; 0.76). Plasma galectin-9 and osteopontin levels had an AUC &gt; 0.8. IFN-\u03b3, TNF-\u03b1 and IL-12 levels were also significantly raised (AUC values &gt; 0.95) while levels of GM-CSF and IL-6 were significantly low in HIV TB coinfection. The ROC analysis revealed the highest diagnostic accuracy of IL-12, indicating its potential as an adjunct immunological biomarker in identifying TB among HIV-infected individuals. However, a large-scale prospective study is required to confirm the findings and to understand their role in predicting the development of tuberculosis disease in people living with HIV.<\/jats:p>","DOI":"10.3390\/ijms27135854","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of IL-12 Levels in Diagnosing Tuberculosis Among People Living with HIV Receiving Antiretroviral Therapy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-2128","authenticated-orcid":false,"given":"Ashwini","family":"Shete","sequence":"first","affiliation":[{"name":"ICMR Indian Council of Medical Research\u2014National Institute of Translational Virology and AIDS Research (ICMR-NITVAR, Formerly National AIDS Research Institute), Pune 411026, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Ghate","sequence":"additional","affiliation":[{"name":"ICMR Indian Council of Medical Research\u2014National Institute of Translational Virology and AIDS Research (ICMR-NITVAR, Formerly National AIDS Research Institute), Pune 411026, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandip","family":"Patil","sequence":"additional","affiliation":[{"name":"ICMR Indian Council of Medical Research\u2014National Institute of Translational Virology and AIDS Research (ICMR-NITVAR, Formerly National AIDS Research Institute), Pune 411026, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3903-2830","authenticated-orcid":false,"given":"Pallavi","family":"Shidhaye","sequence":"additional","affiliation":[{"name":"ICMR Indian Council of Medical Research\u2014National Institute of Translational Virology and AIDS Research (ICMR-NITVAR, Formerly National AIDS Research Institute), Pune 411026, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharati","family":"Mahajan","sequence":"additional","affiliation":[{"name":"ICMR Indian Council of Medical Research\u2014National Institute of Translational Virology and AIDS Research (ICMR-NITVAR, Formerly National AIDS Research Institute), Pune 411026, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5682-6835","authenticated-orcid":false,"given":"Hiroko","family":"Iwasaki-Hozumi","sequence":"additional","affiliation":[{"name":"Research Institute of Health and Welfare, Kibi International University, Takahashi 716-0018, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsuba","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Kyushu University of Medical Sciences, Nobeoka 882-8508, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0947-7625","authenticated-orcid":false,"given":"Toshio","family":"Hattori","sequence":"additional","affiliation":[{"name":"Research Institute of Health and Welfare, Kibi International University, Takahashi 716-0018, Japan"},{"name":"The Shizuoka Graduate University of Public Health, Shizuoka City 420-0881, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","unstructured":"Global Programme on Tuberculosis and Lung Health (GTB) (2020). Global Tuberculosis Report 2020, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gao, J., Zheng, P., and Fu, H. (2013). Prevalence of TB\/HIV co-infection in countries except China: A systematic review and meta-analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064915"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1186\/s12879-019-4569-z","article-title":"Incidence of tuberculosis in HIV-infected adults on first- and second-line antiretroviral therapy in India","volume":"19","author":"Gupte","year":"2019","journal-title":"BMC Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Domingo-Gonzalez, R., Prince, O., Cooper, A., and Khader, S.A. (2016). Cytokines and Chemokines in Mycobacterium tuberculosis Infection. Microbiol. Spectr., 4.","DOI":"10.1128\/microbiolspec.TBTB2-0018-2016"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.jinf.2012.11.005","article-title":"Plasma cytokines and chemokines differentiate between active disease and non-active tuberculosis infection","volume":"66","author":"Mihret","year":"2013","journal-title":"J. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101470","DOI":"10.1016\/j.eclinm.2022.101470","article-title":"Assessment of tuberculosis disease activity in people infected with Mycobacterium tuberculosis and living with HIV: A longitudinal cohort study","volume":"49","author":"Kroidl","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107876","DOI":"10.1016\/j.ijid.2025.107876","article-title":"Tuberculosis and HIV coinfection: Progress and challenges towards reducing incidence and mortality","volume":"155","author":"Sossen","year":"2025","journal-title":"Int. J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103787","DOI":"10.1016\/j.ebiom.2021.103787","article-title":"Plasma host protein biomarkers correlating with increasing Mycobacterium tuberculosis infection activity prior to tuberculosis diagnosis in people living with HIV","volume":"75","author":"Singer","year":"2022","journal-title":"EBioMedicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e515","DOI":"10.1016\/S2352-3018(18)30137-1","article-title":"Sensitivity and specificity of WHO\u2019s recommended four-symptom screening rule for tuberculosis in people living with HIV: A systematic review and meta-analysis","volume":"5","author":"Hamada","year":"2018","journal-title":"Lancet HIV"},{"key":"ref_10","unstructured":"World Health Organization (2014). High-Priority Target Product Profiles for New Tuberculosis Diagnostics: Report of a Consensus Meeting, World Health Organization."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.2147\/COPD.S111254","article-title":"Platelet-lymphocyte ratios: A potential marker for pulmonary tuberculosis diagnosis in COPD patients","volume":"11","author":"Chen","year":"2016","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bjid.2014.10.008","article-title":"Ratio of monocytes to lymphocytes in peripheral blood in patients diagnosed with active tuberculosis","volume":"19","author":"Wang","year":"2015","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1093\/cid\/ciab729","article-title":"Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment","volume":"74","author":"Owolabi","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"337","DOI":"10.18585\/inabj.v13i4.1698","article-title":"Higher Neutrophil-lymphocyte Ratio in TB\/HIV Co-infection Compared to Pulmonary Tuberculosis","volume":"13","author":"Sulastri","year":"2021","journal-title":"Indones. Biomed. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3343\/alm.2013.33.2.105","article-title":"Role of the neutrophil-lymphocyte count ratio in the differential diagnosis between pulmonary tuberculosis and bacterial community-acquired pneumonia","volume":"33","author":"Yoon","year":"2013","journal-title":"Ann. Lab. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7052","DOI":"10.21037\/jtd-24-1585","article-title":"The diagnostic value of hydroxyproline combined with tuberculosis infection T lymphocyte spot assay in pulmonary tuberculosis","volume":"16","author":"Zhai","year":"2024","journal-title":"J. Thorac. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, F., Chen, D., Zeng, Q., and Du, Y. (2023). Possible Mechanisms of Lymphopenia in Severe Tuberculosis. Microorganisms, 11.","DOI":"10.3390\/microorganisms11112640"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4103\/0970-2113.53230","article-title":"Alkaline phosphatase: Distinguishing between tuberculous and nontuberculous pleural effusion","volume":"26","author":"Jadhav","year":"2009","journal-title":"Lung India"},{"key":"ref_19","first-page":"22","article-title":"Alkaline Phosphatase Levels in Tuberculous Cervical Lymphadenitis\u2014Could it be a Predictor for Diagnosis and Monitoring Response to Anti-tuberculous Treatment","volume":"2","author":"Kailas","year":"2016","journal-title":"IJSS J. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Reeve, B.W., Ndlangalavu, G., Mishra, H., Palmer, Z., Tshivhula, H., Rockman, L., Naidoo, S., Mbu, D.L., Naidoo, C.C., and Derendinger, B. (2023). Point-of-care C-reactive protein and Xpert MTB\/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: A prospective diagnostic accuracy study. medRxiv.","DOI":"10.1101\/2023.05.30.23290716"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S1473-3099(17)30488-7","article-title":"Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: A diagnostic accuracy study","volume":"17","author":"Yoon","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s12879-021-05916-z","article-title":"Pulmonary tuberculosis screening in anti-retroviral treated adults living with HIV in Kenya","volume":"21","author":"Gersh","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4103\/ijmy.ijmy_63_20","article-title":"Plasma levels of tumor necrosis factor-alpha, interferon-gamma, inducible nitric oxide synthase, and 3-nitrotyrosine in drug-resistant and drug-sensitive pulmonary tuberculosis patients, Ibadan, Nigeria","volume":"9","author":"Bolajoko","year":"2020","journal-title":"Int. J. Mycobacteriol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.sjbs.2021.10.002","article-title":"Assessment of IL-12, mRNA expression, vitamin-D level, and their correlation among the Mycobacterium tuberculosis cases","volume":"29","author":"Abohashrh","year":"2022","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Singh, S.B., and Lin, H.C. (2021). Role of Intestinal Alkaline Phosphatase in Innate Immunity. Biomolecules, 11.","DOI":"10.3390\/biom11121784"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Klinder, A., Waletzko-Hellwig, J., Sellin, M.L., Seyfarth-Sehlke, A., Wolfien, M., Prehn, F., Bader, R., and Jonitz-Heincke, A. (2022). Effects of the Interleukin-6 Receptor Blocker Sarilumab on Metabolic Activity and Differentiation Capacity of Primary Human Osteoblasts. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14071390"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.tube.2018.08.006","article-title":"Diagnostic performance of GM-CSF and IL-2 in response to long-term specific-antigen cell stimulation in patients with active and latent tuberculosis infection","volume":"112","author":"Balcells","year":"2018","journal-title":"Tuberculosis"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mishra, A., Singh, V.K., Jagannath, C., Subbian, S., Restrepo, B.I., Gauduin, M.C., and Khan, A. (2022). Human Macrophages Exhibit GM-CSF Dependent Restriction of Mycobacterium tuberculosis Infection via Regulating Their Self-Survival, Differentiation and Metabolism. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.859116"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shete, A., Bichare, S., Pujari, V., Virkar, R., Thakar, M., Ghate, M., Patil, S., Vyakarnam, A., Gangakhedkar, R., and Bai, G. (2020). Elevated Levels of Galectin-9 but Not Osteopontin in HIV and Tuberculosis Infections Indicate Their Roles in Detecting MTB Infection in HIV Infected Individuals. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01685"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Dunsmore, G., Rosero, E.P., Shahbaz, S., Santer, D.M., Jovel, J., Lacy, P., Houston, S., and Elahi, S. (2021). Neutrophils promote T-cell activation through the regulated release of CD44-bound Galectin-9 from the cell surface during HIV infection. PLoS Biol., 19.","DOI":"10.1371\/journal.pbio.3001387"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Horio, Y., Ichiyasu, H., Kojima, K., Saita, N., Migiyama, Y., Iriki, T., Fujii, K., Niki, T., Hirashima, M., and Kohrogi, H. (2017). Protective effect of Galectin-9 in murine model of lung emphysema: Involvement of neutrophil migration and MMP-9 production. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180742"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Khambati, N., Olbrich, L., Ellner, J., Salgame, P., Song, R., and Bijker, E.M. (2021). Host-Based Biomarkers in Saliva for the Diagnosis of Pulmonary Tuberculosis in Children: A Mini-Review. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.756043"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shete, A., Ghate, M., Iwasaki-Hozumi, H., Patil, S., Shidhaye, P., Bai, G., Matsuba, T., Pharande, P., Mahajan, B., and Randive, A. (2024). Dynamics of Matricellular Protein Levels in Blood Predict Recovery in Patients with Human Immunodeficiency Virus-Tuberculosis Coinfection. Viruses, 16.","DOI":"10.3390\/v16050664"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shete, A., Ghate, M., Iwasaki-Hozumi, H., Patil, S., Shidhaye, P., Matsuba, T., Bai, G., Pharande, P., and Hattori, T. (2024). Association of SARS-CoV-2 Seropositivity with Persistent Immune Activation in HIV\/Tuberculosis Co-Infected Patients. Reports, 7.","DOI":"10.3390\/reports7030061"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5854\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:57:29Z","timestamp":1782968249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":34,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135854"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135854","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]}}}