Large‐Scale Proteome Profiling Identifies Biomarkers Associated with Suspected Neurosyphilis Diagnosis

Author:

Li Jun12ORCID,Ma Jie3ORCID,Liu MingJuan1ORCID,Li Mansheng3ORCID,Zhang Ming4,Yin Wenhao5,Wu Mengyin1,Li Xiao3,Zhang Qiyu12,Zhang Hanlin1ORCID,Zheng Heyi1,Mao Chenhui6,Sun Jian7,Wang Wenze7,Lyu Wei8,Yue Xueping9,Weng Wenjia4,Li Juan4,Chen Fengxin10,Zhu Yunping311ORCID,Leng Ling2ORCID

Affiliation:

1. Department of Dermatology Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College National Clinical Research Center for Dermatologic and Immunologic Diseases Beijing 100730 China

2. Stem cell and Regenerative Medicine Lab Department of Medical Science Research Center Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Translational Medicine Center Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100730 China

3. State Key Laboratory of Medical Proteomics Beijing Proteome Research Center National Center for Protein Sciences (Beijing) Beijing Institute of Lifeomics Beijing 102206 China

4. Department of Dermatology Beijing Youan Hospital Capital Medical University Beijing 100069 China

5. The First Hospital of Jiaxing The Affiliated Hospital of Jiaxing University Zhejiang 314001 China

6. Department of Neurology Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Science Beijing 100730 China

7. Department of Pathology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China

8. Department of Infectious Disease Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China

9. Department of Dermatology and Venereology Beijing Tiantan Hospital Capital Medical University Beijing 100050 China

10. Infections Disease Center Beijing Ditan Hospital Capital Medical University Beijing 100102 China

11. Basic Medical School Anhui Medical University Anhui 230032 China

Abstract

AbstractNeurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as “the great imitator,” NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients.

Funder

National Natural Science Foundation of China

Beijing Science and Technology Planning Project

Chinese Academy of Medical Sciences Initiative for Innovative Medicine

Peking Union Medical College Hospital

Publisher

Wiley

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