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Cytotoxic T-cell deficiency and sustained B-cell activation in serofast syphilis: a prospective observational study

Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction: 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. Methods: 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. Results: ) compared with serologically cured individuals, a difference that persisted after treatment (all p<0.05). Six months post-treatment, serofast patients showed higher B-cell counts (p<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. Discussion: 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.
Language: English
Subfield: Physiology
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7141395680
FWCI:
Cites: 27
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