{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:58Z","timestamp":1787026618308,"version":"build-2736575974"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"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>Background<\/jats:title>\n                    <jats:p>\n                      In approximately 20% of patients with early syphilis, the classical serological response pattern is absent following treatment. They experience a serofast state, which manifests as less than a 4-fold decline in non-treponemal titres, without any clinical signs of treatment failure or reinfection. The effectiveness of the immune defense against\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      , as well as its potential failure and the occurrence of the serofast state, depends on the Th1 cellular response, including cytokines such as IFN-\u03b3. The aim of this prospective observational study was to investigate the impact of IFN-\u03b3 gene polymorphisms on the occurrence of the serofast state.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A cohort of 97 patients with early syphilis (73.2% secondary syphilis, 26.8% early latent syphilis) and 50 healthy volunteers were enrolled. Two single nucleotide polymorphisms (SNPs) in the IFN-\u03b3 gene promoter region, +874 T&amp;gt;A (rs2430561) and +2109 A&amp;gt;G (rs1861494), were analyzed. Serum IFN-\u03b3 levels were measured at baseline, prior to treatment. Patients were stratified into serofast (n=18) and serologically cured (n=79) groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serofast patients exhibited significantly lower baseline serum IFN-\u03b3 levels compared to the serologically cured group (p=0.01). All healthy subjects had IFN-\u03b3 levels below the detection limit. Analysis of IFN-\u03b3 gene polymorphisms revealed a significant association with treatment outcomes. The +874 AA and +2109 GG genotypes, associated with low IFN-\u03b3 production, were significantly more frequent in serofast patients (p=0.0004 and p=0.002, respectively), with odds ratios (OR) of 7.1 (95% CI: 2.2-23.2) and 5.5 (95% CI: 1.8-17.3), respectively. Additionally, carriers of the +874A\/+2109G haplotype were significantly more likely to remain serofast (OR 4.4, p=0.01). Conversely, the +874 TT and +2109 AA genotypes, associated with high IFN-\u03b3 production, were significantly linked to serological cure (OR 4.4, p=0.03; OR 4.4, p=0.01). Similarly, the +874T\/+2109A haplotype was strongly associated with serological cure (OR 17.9, p&amp;lt;0.0001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Distinct IFN-\u03b3 polymorphisms and haplotypes are associated with serological outcomes in syphilis. The +874 T&amp;gt;A and +2109 A&amp;gt;G variants influence IFN-\u03b3 levels, potentially modulating the immune response and serological recovery. These findings suggest a genetic predisposition underlying serofast syphilis and underscore the importance of personalized approaches in its management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1602527","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T01:23:05Z","timestamp":1748827385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"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 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