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An Exploratory Study of Host Plasma Proteomic Signatures that Distinguish Active Syphilis in Adults

Chou, C.; Morton, S. R.; Konda, K. A.; Vargas, S.; Reyes-Diaz, M.; Vasquez, F.; Caceres, C.; Klausner, J. D.; Toombs, T.; Ahmad, R.; Allan-Blitz, L.-T.

2026-03-05 infectious diseases
10.64898/2026.03.04.26347505 medRxiv
Show abstract

Syphilis remains a major public health concern. However, current serologic assays are limited in their ability to distinguish active from previously treated disease. We applied tandem mass tag-based quantitative proteomics to plasma from 10 adults with active syphilis and 10 age- and gender-matched non-diseased controls. We identified 54 differentially regulated proteins (36 upregulated, 18 downregulated). Those proteins map to immune and inflammatory responses, acute-phase signaling, coagulation and vascular pathways, and cellular stress processes. Three sets of between 2-5 proteins achieved >99% discrimination between cases and controls. Our exploratory findings support proteomics as a potential tool to develop novel syphilis diagnostics.

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