{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:44:13Z","timestamp":1791870253388,"version":"4.3.4"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leducq PRIMA Grant, CNPq, FAPEMIG, INCT-DT"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Rheumatic heart disease (RHD) remains a major cause of preventable morbidity in low- and middle-income countries. As the most serious sequel of acute rheumatic fever (ARF) caused by Streptococcus pyogenes, RHD arises from molecular mimicry that drives autoimmune damage of cardiac valves. We systematically reviewed human studies (1977\u20132025) following PRISMA to clarify systemic immune signatures associated with valvular pathology. Searches of PubMed, LILACS, ScienceDirect, and Web of Science found 29 studies: 22 RHD and 7 ARF. In ARF, elevations in IL-6, IL-8, IL-17F, GM-CSF, TNF-a, and CXCL10 occurred alongside increased activity of CD4+ Th1 and MAIT cells. In RHD, a consistent inflammatory\u2013fibrotic profile emerged with raised IL-17, IFN-\u03b3, TNF-a, TGF-\u03b21, Tenascin-C, and prothymosin alpha (ProT\u03b1) in blood and valve tissue. CD4+ and CD8+ T cells were implicated in valve injury; ProT\u03b1 correlated with cytotoxic activity of circulating CD8+ T cells. Several mediators (IL-6, TNF-a, IL-8, CXCL10, CCL2, CCL19) were identified in RHD studies as being associated with inflammation, cell recruitment, and clinical severity. Systemic dysregulation mirrored local valve inflammation, suggesting circulating molecules may index ongoing cardiac damage. These findings underscore a central role for T cells and pro-inflammatory cytokines in RHD and highlight candidate prognostic markers and therapeutic targets to inform translational studies and trials.<\/jats:p>","DOI":"10.3390\/pathogens14111185","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T12:55:31Z","timestamp":1763556931000},"page":"1185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Systemic Soluble and Cellular Immune Response in Acute Rheumatic Fever and Rheumatic Heart Disease: A Systematic Review of Human Studies"],"prefix":"10.3390","volume":"14","author":[{"given":"Ana Luiza da Silva","family":"Resende","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia das Intera\u00e7\u00f5es Celulares, Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Avenida. Presidente Ant\u00f4nio Carlos, Pampulha, Belo Horizonte 6627, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eula Graciele Amorim","family":"Neves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia das Intera\u00e7\u00f5es Celulares, Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Avenida. Presidente Ant\u00f4nio Carlos, Pampulha, Belo Horizonte 6627, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda Martins","family":"Cavalcante","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia das Intera\u00e7\u00f5es Celulares, Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Avenida. Presidente Ant\u00f4nio Carlos, Pampulha, Belo Horizonte 6627, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7586-9996","authenticated-orcid":false,"given":"Walderez Ornelas","family":"Dutra","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia das Intera\u00e7\u00f5es Celulares, Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Avenida. Presidente Ant\u00f4nio Carlos, Pampulha, Belo Horizonte 6627, MG, Brazil"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Doen\u00e7as Tropicais, INCT-DT, Salvador 40110-160, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0140-6736(05)66874-2","article-title":"Acute rheumatic fever","volume":"366","author":"Carapetis","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0140-6736(18)30999-1","article-title":"Acute rheumatic fever","volume":"392","author":"Karthikeyan","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e717","DOI":"10.1016\/S2214-109X(14)70310-9","article-title":"Active surveillance for rheumatic heart disease in endemic regions: A systematic review and meta-analysis of prevalence among children and adolescents","volume":"2","author":"Stortecky","year":"2014","journal-title":"Lancet Glob. 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