{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:10:55Z","timestamp":1771931455362,"version":"3.50.1"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The complement system plays a vital role in the immune response against tuberculosis (TB), aiding in the recognition and clearance of Mycobacterium tuberculosis. However, its imbalance can result in either insufficient immune activation or excessive inflammation, both of which may contribute to poor treatment outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigates whether baseline complement profiles are associated with unfavorable treatment responses in pulmonary TB patients. Using the Magpix multiplex cytokine assay, plasma levels of complement components (C2, C3, C3b\/iC3b, C4, C4b, C5, C5a, C1q, MBL) and regulatory proteins (Factor B, Factor D, Factor H, Factor I) were measured in TB patients with poor treatment outcomes (n=68) and disease-free controls (n=108).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At both baseline (pre-treatment) and month two of anti-TB therapy, cases had significantly elevated levels of C3, C3b, C4b, C5, C5a, and C1q, and reduced levels of Factor B and Factor H compared to controls. Regression modelling revealed that C3, C3b, C4b, C5, C5a and C1q were associated with increased risk of unfavorable outcomes in unadjusted and adjusted analyses in the study cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that early and sustained complement activation, particularly through the classical pathway, is associated with adverse outcomes in TB. Complement dysregulation may thus serve as a potential prognostic marker for identifying individuals at risk of poor treatment response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1679947","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T06:50:57Z","timestamp":1770792657000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Complement profiling for treatment outcomes in pulmonary TB"],"prefix":"10.3389","volume":"17","author":[{"given":"Nathella","family":"Pavan Kumar","sequence":"first","affiliation":[{"name":"Indian Council of Medical Research (ICMR)- National Institute for Research in Tuberculosis","place":["Chennai, India"]},{"name":"Academy of Scientific and Innovative Research","place":["Ghaziabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arul","family":"Nancy P.","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research (ICMR)- National Institute for Research in Tuberculosis","place":["Chennai, India"]},{"name":"National Institutes of Health-NIRT- International Center for Excellence in Research","place":["Chennai, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed","family":"Hissar","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research (ICMR)- National Institute for Research in Tuberculosis","place":["Chennai, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanmugam","family":"Sivakumar","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research (ICMR)- National Institute for Research in Tuberculosis","place":["Chennai, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"Prof. M. Viswanathan Diabetes Research Center","place":["Chennai, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramalingam","family":"Bethunaickan","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research (ICMR)- National Institute for Research in Tuberculosis","place":["Chennai, India"]},{"name":"Academy of Scientific and Innovative Research","place":["Ghaziabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hardy","family":"Kornfeld","sequence":"additional","affiliation":[{"name":"University of Massachusetts Chan Medical School","place":["Worcester, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subash","family":"Babu","sequence":"additional","affiliation":[{"name":"National Institutes of Health-NIRT- International Center for Excellence in Research","place":["Chennai, India"]},{"name":"Laboratory of Parasitic Diseases (LPD), of National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)","place":["Bethesda, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.419","article-title":"Mycobacterium tuberculosis: immune\u00a0response, biomarkers, and therapeutic intervention","volume":"5","author":"Zhuang","year":"2024","journal-title":"MedComm (2020)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00350","article-title":"Immune response to mycobacterium tuberculosis: A narrative review","volume":"7","author":"de Martino","year":"2019","journal-title":"Front Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1007\/s11274-023-03636-x","article-title":"Clinical manifestations and immune response to tuberculosis","volume":"39","author":"Carabali-Isajar","year":"2023","journal-title":"World J Microbiol Biotechnol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3390\/medicina57020084","article-title":"The role of complement system and the immune response to\u00a0tuberculosis infection","volume":"57","author":"Jagatia","year":"2021","journal-title":"Medicina (Kaunas)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1093640","article-title":"Chitinase and indoleamine 2, 3-dioxygenase are prognostic biomarkers for unfavorable treatment outcomes in pulmonary tuberculosis","volume":"14","author":"Kumar","year":"2023","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2014.027","article-title":"Immunology of tuberculosis","volume":"6","author":"Bozzano","year":"2014","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00257","article-title":"Complement system part II: role in immunity","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/cr.2009.139","article-title":"Complement and its role in innate and adaptive immune responses","volume":"20","author":"Dunkelberger","year":"2010","journal-title":"Cell Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"101672","DOI":"10.1016\/j.smim.2022.101672","article-title":"Inflammation-mediated tissue damage in pulmonary tuberculosis and host-directed therapeutic strategies","volume":"65","author":"Tiwari","year":"2023","journal-title":"Semin Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/978-0-387-71767-8_8","article-title":"Role of MBL-associated serine protease (MASP) on activation of the lectin complement pathway","volume":"598","author":"Takahashi","year":"2007","journal-title":"Adv Exp Med Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"101339","DOI":"10.1016\/j.smim.2019.101339","article-title":"Complement activation and regulation in rheumatic disease","volume":"45","author":"Dijkstra","year":"2019","journal-title":"Semin Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00530","article-title":"Assessment of the role of C3(H(2)O) in the alternative pathway","volume":"11","author":"Fromell","year":"2020","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2013.08.001","article-title":"Overview of complement activation and regulation","volume":"33","author":"Noris","year":"2013","journal-title":"Semin Nephrol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1104","article-title":"Plasma chemokines are baseline predictors of unfavorable treatment outcomes in pulmonary tuberculosis","volume":"73","author":"Kumar","year":"2021","journal-title":"Clin Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.27754","article-title":"Association of plasma matrix metalloproteinase and tissue inhibitors of matrix metalloproteinase levels with adverse treatment outcomes among patients with pulmonary tuberculosis","volume":"3","author":"Kumar","year":"2020","journal-title":"JAMA Netw Open"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2418-4","article-title":"Complement factor H in host defense and immune evasion","volume":"74","author":"Parente","year":"2017","journal-title":"Cell Mol Life Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.123.2.529","article-title":"The alternative pathway C3\/C5 convertase: chemical basis of factor B activation","volume":"123","author":"Lesavre","year":"1979","journal-title":"J Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1679947\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:22:38Z","timestamp":1771928558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1679947\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":17,"alternative-id":["10.3389\/fimmu.2026.1679947"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1679947","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]},"article-number":"1679947"}}