Abstract
Neurosyphilis (NS) is a chronic central nervous system infection caused by Treponema pallidum. Owing to its diverse clinical manifestations and the limited sensitivity of current diagnostic methods, NS is difficult to diagnose. Understanding the molecular mechanisms of NS and identifying reliable biomarkers are essential for improving diagnostic and therapeutic strategies. This study employed Mendelian randomization (MR) analysis to explore the causal relationships among protein ratio quantitative trait loci (rQTLs), cerebrospinal fluid (CSF) metabolites, and syphilis risk at various stages. The results revealed that several rQTLs, including CD46/TNFRSF14 and TBC1D23/TBC1D5, were closely associated with syphilis risk, whereas others, such as BANK1/HEXIM1 and GOPC/HEXIM1, exhibited protective effects. Mediation analysis further identified key CSF metabolites, such as N-acetyltaurine and bilirubin, as important mediators linking rQTLs and syphilis progression. Through integrated analysis of cis-proteins from rQTLs and transcriptomic data from CD4 + T-cells of NS patients, METAP2 was identified as a key biomarker in NS, with the potential mechanisms elucidated. Importantly, T. pallidum may inhibit CD4 + T-cell proliferation by modulating METAP2, thereby accelerating disease progression. These findings offer new insights into the pathogenesis of NS and highlight METAP2 as a potential biomarker, laying a foundation for improving diagnostic and therapeutic strategies.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 University of South China, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918)
2 University of South China, MOE Key Lab of Rare Pediatric Diseases&Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918)
3 University of South China, School of Public Health, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918)
4 University of South China, MOE Key Lab of Rare Pediatric Diseases&Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); University of South China, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); University of South China, Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Department of Clinical Laboratory Medicine, The First Affiliated Hospital, Hengyang Medical College, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918)
5 University of South China, MOE Key Lab of Rare Pediatric Diseases&Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); University of South China, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); Changsha Central Hospital, Department of Clinical Laboratory Medicine, Changsha, People’s Republic of China (GRID:grid.452210.0); University of South China, School of Public Health, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); University of South China, Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Department of Clinical Laboratory Medicine, The First Affiliated Hospital, Hengyang Medical College, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918)