An integrated immunopathological model of syphilis serofast: a systematic review and meta-analysis

The immunological mechanisms underlying the syphilis serofast remain incompletely elucidated. This systematic review and meta-analysis aims to quantify the association between key immune indicators and serofast.

We systematically searched PubMed, Embase, Web of Science, Google Scholar and Chinese databases (CNKI, VIP, and CBMdisc) until December 31, 2024, for case-control, cross-sectional or cohort studies meeting serofast criteria (RPR/TRUST titer ≤1:8 persisting for ≥12 months). Random-effects models were used to calculate standardized mean differences (SMD) with 95% confidence intervals (CIs). The risk of bias was assessed using the Newcastle-Ottawa Scale (for observational studies) by two independent reviewers.

A total of 38 studies involving 5082 patients were included. The serofast group exhibited significant immune dysregulation: (1) Cellular immune suppression:decreased CD4+ T cells (SMD=-0.61, I²=33.5%) and increased CD8+ T cells (SMD = 0.40, I²=66.7%), leading to an inverted CD4+/CD8+ ratio (SMD=-0.44, I²=64.7%); (2) Th1/Th2 shift:suppression of Th1 cytokines (e.g., IFN-γ, SMD=-2.19, I²=95.7%) with a predominant Th2 response (e.g., IL-10, SMD =+ 2.63,I²=92.5%); (3) Humoral abnormalities: persistently elevated IgM (SMD = 0.96,I²=94.4%) and complement consumption (C3,SMD=-0.60, I²=89.0%; C4, SMD=-0.80, I²=87.6%); (4) Signaling dysregulation: downregulated TLR2 expression and disordered chemokine receptors (TLR2 mRNA,SMD=-1.52, I²=36.0%).The substantial heterogeneity (I² > 50%) observed in several analyses was explored in subgroup and sensitivity analyses, as detailed in the main text.

The serofast is characterized by a cascade of "cellular immune suppression-Th1/Th2 shift-complement exhaustion." Our findings establish a quantified immunological basis for the serofast state and suggest potential targets for immunomodulatory therapy.

https://www.crd.york.ac.uk/prospero/, identifier CRD420251156478.