Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia

Menghui Yao; Shuolin Wang; Yingdong Han; He Zhao; Yue Yin; Yun Zhang; Xuejun Zeng

doi:10.1186/s12967-023-04477-w

Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia

J Transl Med. 2023 Sep 5;21(1):594. doi: 10.1186/s12967-023-04477-w.

Authors

Menghui Yao¹, Shuolin Wang¹, Yingdong Han¹, He Zhao¹, Yue Yin¹, Yun Zhang², Xuejun Zeng³

Affiliations

¹ Division of General Internal Medicine, Department of Family Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, 100730, China.
² Division of General Internal Medicine, Department of Family Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, 100730, China. zhangyun10806@pumch.cn.
³ Division of General Internal Medicine, Department of Family Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, 100730, China. zxjpumch@126.com.

Abstract

Background: Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status.

Methods: The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model.

Results: The patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer-Lemeshow goodness-of-fit test (χ² = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable.

Conclusion: Micro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.

Keywords: Dendritic cells; Depression; Fibromyalgia; Micro-inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Cluster Analysis
Fibromyalgia*
Humans
Immunity, Innate
Inflammation