Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders

Abstract Background Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood. Methods To investigate this, we employed a multi-omics approac...

Full description

Saved in:
Bibliographic Details
Main Authors: Zuoquan Xie, Qinming Zhou, Jin Hu, Lu He, Huangyu Meng, Xiaoni Liu, Guangqiang Sun, Zhiyu Luo, Yuan Feng, Liang Li, Xingkun Chu, Chen Du, Dabing Yang, Xinying Yang, Jing Zhang, Changrong Ge, Xiang Zhang, Sheng Chen, Meiyu Geng
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-024-05801-8
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850179753574662144
author Zuoquan Xie
Qinming Zhou
Jin Hu
Lu He
Huangyu Meng
Xiaoni Liu
Guangqiang Sun
Zhiyu Luo
Yuan Feng
Liang Li
Xingkun Chu
Chen Du
Dabing Yang
Xinying Yang
Jing Zhang
Changrong Ge
Xiang Zhang
Sheng Chen
Meiyu Geng
author_facet Zuoquan Xie
Qinming Zhou
Jin Hu
Lu He
Huangyu Meng
Xiaoni Liu
Guangqiang Sun
Zhiyu Luo
Yuan Feng
Liang Li
Xingkun Chu
Chen Du
Dabing Yang
Xinying Yang
Jing Zhang
Changrong Ge
Xiang Zhang
Sheng Chen
Meiyu Geng
author_sort Zuoquan Xie
collection DOAJ
description Abstract Background Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood. Methods To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP). Results Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression. Conclusions Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.
format Article
id doaj-art-e3952ee527f34a49be4aefe9a3a8f255
institution OA Journals
issn 1479-5876
language English
publishDate 2024-11-01
publisher BMC
record_format Article
series Journal of Translational Medicine
spelling doaj-art-e3952ee527f34a49be4aefe9a3a8f2552025-08-20T02:18:25ZengBMCJournal of Translational Medicine1479-58762024-11-0122111810.1186/s12967-024-05801-8Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disordersZuoquan Xie0Qinming Zhou1Jin Hu2Lu He3Huangyu Meng4Xiaoni Liu5Guangqiang Sun6Zhiyu Luo7Yuan Feng8Liang Li9Xingkun Chu10Chen Du11Dabing Yang12Xinying Yang13Jing Zhang14Changrong Ge15Xiang Zhang16Sheng Chen17Meiyu Geng18State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesDepartment of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Neurology, Affiliated Hospital of Jiaxing UniversityDepartment of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Neurology, Huashan Hospital Fudan University and Institute of Neurology, Fudan UniversityShanghai Green Valley Pharmaceutical Co., LtdShanghai Green Valley Pharmaceutical Co., LtdShanghai Green Valley Pharmaceutical Co., LtdShanghai Green Valley Pharmaceutical Co., LtdShanghai Green Valley Pharmaceutical Co., LtdShanghai Green Valley Pharmaceutical Co., LtdShanghai Green Valley Pharmaceutical Co., LtdShanghai Green Valley Pharmaceutical Co., LtdShanghai Green Valley Pharmaceutical Co., LtdShanghai Green Valley Pharmaceutical Co., LtdDepartment of Neurology, Huashan Hospital Fudan University and Institute of Neurology, Fudan UniversityDepartment of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesAbstract Background Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood. Methods To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP). Results Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression. Conclusions Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.https://doi.org/10.1186/s12967-024-05801-8Neuromyelitis optica spectrum disordersBlood immune cells phenotypingPlasma cytokine arrayPlasma metabolomicsBiomarker
spellingShingle Zuoquan Xie
Qinming Zhou
Jin Hu
Lu He
Huangyu Meng
Xiaoni Liu
Guangqiang Sun
Zhiyu Luo
Yuan Feng
Liang Li
Xingkun Chu
Chen Du
Dabing Yang
Xinying Yang
Jing Zhang
Changrong Ge
Xiang Zhang
Sheng Chen
Meiyu Geng
Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders
Journal of Translational Medicine
Neuromyelitis optica spectrum disorders
Blood immune cells phenotyping
Plasma cytokine array
Plasma metabolomics
Biomarker
title Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders
title_full Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders
title_fullStr Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders
title_full_unstemmed Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders
title_short Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders
title_sort integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders
topic Neuromyelitis optica spectrum disorders
Blood immune cells phenotyping
Plasma cytokine array
Plasma metabolomics
Biomarker
url https://doi.org/10.1186/s12967-024-05801-8
work_keys_str_mv AT zuoquanxie integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT qinmingzhou integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT jinhu integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT luhe integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT huangyumeng integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT xiaoniliu integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT guangqiangsun integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT zhiyuluo integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT yuanfeng integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT liangli integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT xingkunchu integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT chendu integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT dabingyang integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT xinyingyang integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT jingzhang integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT changrongge integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT xiangzhang integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT shengchen integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders
AT meiyugeng integratedomicsprofilingrevealssystemicdysregulationandpotentialbiomarkersinthebloodofpatientswithneuromyelitisopticaspectrumdisorders