{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:48:24Z","timestamp":1774594104342,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"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 serofast state, defined by persistent non-treponemal reactivity after adequate therapy for syphilis, remains a clinically relevant yet poorly understood condition. Whether serofast reflects residual infection or persistent immune activation remains uncertain. We aimed to characterize peripheral blood lymphocyte subpopulations and anticardiolipin antibodies in patients with serofast syphilis and compare them with individuals achieving a serological cure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective observational study including adults with early syphilis treated with benzathine penicillin G. Peripheral blood samples were collected at baseline and six months post-treatment for immunophenotyping and antiphospholipid antibody assessment. Serological outcome was defined by Venereal Disease Research Laboratory (VDRL) response (serofast vs. serologically cured). Twelve healthy volunteers served as controls for anticardiolipin antibody testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 41 included patients, 9 (22%) developed a serofast state. Serofast patients demonstrated significantly lower baseline numbers of cytotoxic T lymphocytes (CD8\n                      <jats:sup>+<\/jats:sup>\n                      and CD3\n                      <jats:sup>+<\/jats:sup>\n                      ) compared with serologically cured individuals, a difference that persisted after treatment (all p&amp;lt;0.05). Six months post-treatment, serofast patients showed higher B-cell counts (p&amp;lt;0.05). Low-level anticardiolipin IgG and IgM were detectable in nearly all patients before treatment but had become undetectable in all participants at six months, while all healthy controls tested negative. No thrombotic events were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Serofast syphilis was associated with reduced cytotoxic T-cell counts and persistent B-cell activation, supporting a model in which impaired cytotoxic clearance of antigen-presenting cells may prolong antibody production despite microbiological cure. The transient nature of infection-induced anticardiolipin antibodies further argues against persistent autoimmunity. These findings provide mechanistic insight into serofast responses and suggest potential immunological determinants of post-treatment serological persistence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1792505","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:19:34Z","timestamp":1774588774000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytotoxic T-cell deficiency and sustained B-cell activation in serofast syphilis: a prospective observational study"],"prefix":"10.3389","volume":"17","author":[{"given":"Konrad","family":"Kamini\u00f3w","sequence":"first","affiliation":[{"name":"Clinical Department of Dermatology in Zabrze, Medical University of Silesia","place":["Katowice, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martyna","family":"Kio\u0142basa","sequence":"additional","affiliation":[{"name":"Clinical Department of Dermatology in Zabrze, Medical University of Silesia","place":["Katowice, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Napi\u00f3rkowska-Baran","sequence":"additional","affiliation":[{"name":"Clinical Department of Dermatology in Zabrze, Medical University of Silesia","place":["Katowice, Poland"]},{"name":"Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toru\u0144","place":["Toru\u0144, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"Pastuszczak","sequence":"additional","affiliation":[{"name":"Clinical Department of Dermatology in Zabrze, Medical University of Silesia","place":["Katowice, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32411-4","article-title":"Syphilis","volume":"389","author":"Hook","year":"2017","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16946","article-title":"2020 European guideline on the management of syphilis","volume":"35","author":"Janier","year":"2021","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir671","article-title":"Predictors of serological cure and serofast state after treatment in HIV-negative persons with early syphilis","volume":"53","author":"Se\u00f1a","year":"2011","journal-title":"Clin Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.rr7301a1","article-title":"CDC laboratory recommendations for syphilis testing, United States, 2024","volume":"73","author":"Papp","year":"2024","journal-title":"MMWR Recomm Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1186\/s12879-015-1209-0","article-title":"A systematic review of syphilis serological treatment outcomes in HIV-infected and HIV-uninfected persons: rethinking the significance of serological non-responsiveness and the serofast state after therapy","volume":"15","author":"Se\u00f1a","year":"2015","journal-title":"BMC Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.13259","article-title":"Treatment of syphilis: a systematic review","volume":"312","author":"Clement","year":"2014","journal-title":"JAMA"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070102","article-title":"Factors associated with serological cure and the serofast state of HIV-negative patients with primary, secondary, latent, and tertiary syphilis","volume":"8","author":"Tong","year":"2013","journal-title":"PloS One"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175477","article-title":"Molecular subtyping of Treponema pallidum and associated factors of serofast status in early syphilis patients: identified novel genotype and cytokine marker","volume":"12","author":"Zhang","year":"2017","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2024.119754","article-title":"Serofast status in syphilis: pathogenesis to therapeutics","volume":"560","author":"Cao","year":"2024","journal-title":"Clin Chim Acta"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12122580","article-title":"The significance of the cell-mediated host immune response in syphilis","volume":"12","author":"Kamini\u00f3w","year":"2024","journal-title":"Microorganisms"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1602527","article-title":"IFN-\u03b3 gene polymorphisms +874 T\/A and +2109 A\/G are associated with the serofast state after early syphilis treatment: a prospective observational study","volume":"16","author":"Kamini\u00f3w","year":"2025","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.5114\/ada.2024.147332","article-title":"Serofast state after syphilis treatment: implications and recommendations for clinical practice. Narrative review","volume":"42","author":"Kio\u0142basa","year":"2025","journal-title":"Postepy Dermatol Alergol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.687534","article-title":"Antiphospholipid antibodies and infection: non nova sed nove","volume":"12","author":"Sciascia","year":"2021","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.5482\/HAMO-16-07-0020","article-title":"Pathophysiological insights into the antiphospholipid syndrome","volume":"37","author":"Lackner","year":"2017","journal-title":"Hamostaseologie"},{"key":"B15","article-title":"Potential predictors for serofast state after treatment among HIV-negative persons with syphilis in China: a systematic review and meta-analysis","volume":"44","author":"Qin","year":"2015","journal-title":"Iran J Public Health"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2021.111540","article-title":"Decreased blood natural killer cells in serofast patients: a systematic review and meta-analysis","volume":"46","author":"Cheng","year":"2021","journal-title":"Cent Eur J Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12879-020-4846-x","article-title":"MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis","volume":"20","author":"Huang","year":"2020","journal-title":"BMC Infect Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002528","article-title":"Regulatory T cells in peripheral blood and cerebrospinal fluid of syphilis patients with and without neurological involvement","volume":"7","author":"Li","year":"2013","journal-title":"PloS NeglTrop Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000001175","article-title":"Predictors of serofast state after treatment of patients with syphilis","volume":"133","author":"Liu","year":"2020","journal-title":"Chin Med J (Engl)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1111\/j.1600-0897.1996.tb00143.x","article-title":"Antiphospholipid antibodies in syphilis","volume":"23","author":"Santiago","year":"1990","journal-title":"Braz J Med Biol Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.11.1106","article-title":"Anticardiolipin, anti-beta(2)-glycoprotein I and antiprothrombin antibodies in black South African patients with infectious disease","volume":"62","author":"Loizou","year":"2003","journal-title":"Ann Rheum Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.9.4081-4084.1994","article-title":"Differences in functional activity of anticardiolipin antibodies from patients with syphilis and those with antiphospholipid syndrome","volume":"62","author":"Pierangeli","year":"1994","journal-title":"Infect Immun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2147\/OARRR.S541224","article-title":"Infection-triggered antiphospholipid syndrome: a critical overview","volume":"17","author":"Smiyan","year":"2025","journal-title":"Open Access Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00140","article-title":"Antigen cross-presentation of immune complexes","volume":"5","author":"Platzer","year":"2014","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.coi.2019.12.005","article-title":"Cross-presentation of exogenous antigens on MHC I molecules","volume":"64","author":"Colbert","year":"2020","journal-title":"Curr Opin Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115927","article-title":"Induction of antiphospholipid autoantibodies by immunization with beta 2 glycoprotein I (apolipoprotein H)","volume":"90","author":"Gharavi","year":"1992","journal-title":"J Clin Invest"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.5.388","article-title":"Antiphospholipid antibodies and infections","volume":"62","author":"Asherson","year":"2003","journal-title":"Ann Rheum Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2007.10.001","article-title":"Antiphospholipid antibodies, antiphospholipid syndrome and infections","volume":"7","author":"S\u00e8ne","year":"2008","journal-title":"Autoimmun Rev"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1792505\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:19:35Z","timestamp":1774588775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1792505\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":28,"alternative-id":["10.3389\/fimmu.2026.1792505"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1792505","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]},"article-number":"1792505"}}