Elevated CD3+ T-cell proportions and a dysregulated cytokine network characterize the Serofast state in treated syphilis: A cross-sectional study of 60 participants.

BACKGROUND

Syphilis serofast, characterized by persistent seropositivity despite adequate treatment and symptom resolution, poses significant clinical challenges. This study investigated the immunological basis of serofast status, focusing on CD3+ T-cell populations and cytokine profiles.

METHODS

This cross-sectional study included 20 healthy controls (HC), 20 serological cure patients (SC), and 20 serofast state patients (SS) with HIV-negative primary syphilis. Blood collection was uniformly performed at the 12-month post-treatment time point. Flow cytometry was used to analyze proportions of CD3+ T-cells in peripheral blood mononuclear cells, and antibody array was utilized to determine cytokine levels.

RESULTS

Serofast patients exhibited significantly elevated proportions of CD3+ T-cells compared to both SC and HC groups (both p < 0.05). A distinct serum cytokine profile was revealed in serofast state group, including significant upregulation of Eotaxin (CCL11), IL-17 A, TGF-β1, ICAM-1, IL-7, IL-15, MIF, IL-10, and MCP-1 (CCL2), and downregulation of IL-2, G-CSF (CSF3), and IL-1Ra (all p < 0.05, SS vs. HC/SC). Bioinformatics identified these 12 dysregulated proteins as critically involved in lymphocyte (especially T-cell) activation, proliferation, and differentiation, linking them mechanistically to CD3+ T-cell function. Linear regression demonstrated significant positive correlations between CD3+ T-cell proportions and TGF-β1, Eotaxin, and IL-17 A levels (all p < 0.05).

CONCLUSIONS

These findings suggest that dysregulated CD3+ T-cell expansion and a specific cytokine imbalance may form a dysfunctional immune axis to promote chronic inflammation and sustain serological positivity, which offers potential targets for novel therapeutic strategies.