Frontiers in Cellular and Infection Microbiology · Published 2026-07-29 · DOI 10.3389/fcimb.2026.1864213
Jing Li, Xiaohan Li, Yike Huang, Fei Ye, Xi Lin, Dongdong Li
ObjectivesThis study aimed to systematically evaluate the disease spectrum, demographic characteristics, and autoantibody profiles associated with biological false-positive (BFP) reactions in serological tests for syphilis.MethodsA retrospective analysis was conducted on 87 patients with TRUST (+)/TPPA (-) results from January 2016 to February 2026 at West China Hospital, Sichuan University. Additionally, serum specimens from 1068 patients (including autoimmune diseases, Epstein-Barr virus infection, malignancy, and lupus anticoagulant positivity) were tested using chemiluminescence immunoassay and toluidine red unheated serum test (TRUST), and the autoantibody profiles of 539 of these patients were analyzed.ResultsAmong retrospective cases, unknown diseases accounted for the highest proportion (34.5%), followed by malignancy (12.6%) and neurological diseases (10.3%). In the cross-sectional case series, autoimmune diseases showed the highest BFP rate (52.3%), particularly rheumatoid arthritis (75.9%), connective tissue disease (62.4%), and Sjögren’s syndrome (52.3%); the false-positive rate was 36.1% in patients with malignancy and 8.5% in patients with lupus anticoagulant positivity. BFP titers were predominantly low (1:1 or 1:2). EBV-positive BFP reactions occurred only in the 1–19 years age group with acute infection. Autoantibody profiling revealed that, among BFP patients with autoimmune diseases, those who were ANA-positive (n=235) exhibited substantially higher positivity rates for U1-snRNP (21.7%), Sm (9.4%), SS-A (60.9%), SS-B (36.6%), CENP B (14.0%), ANuA (24.3%), AHA (15.3%), and ARPA (11.9%), whereas ANA-negative patients (n=28) showed only low positivity for SS-A (25.0%) and Scl-70 (7.1%).ConclusionBFP reactions are most common in autoimmune diseases, particularly SLE, SS, CTD, and RA, and typically present with low TRUST titers. ANA-positive BFP patients exhibit a broad autoantibody profile, while ANA-negative patients show limited positivity. Comprehensive clinical and autoantibody evaluation is essential to avoid misdiagnosis and unnecessary treatment.
Abstract from DOAJ. Public domain (CC0 1.0).
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Li, J., Li, X., Huang, Y., et al. (2026). In-depth evaluation of false-positive biological reactions in the syphilis serological diagnosis: a cross-sectional study with two sampling components. Frontiers in Cellular and Infection Microbiology. https://doi.org/10.3389/fcimb.2026.1864213