Global analysis of protein expression in muscle tissues of dermatomyositis/polymyosisits patients demonstrated an association between dysferlin and human leucocyte antigen A

Yizhi Xiao; Honglin Zhu; Liya Li; Siming Gao; Di Liu; Bingying Dai; Qiuxiang Li; Huiqian Duan; Huan Yang; Quanzhen Li; Huali Zhang; Hui Luo; Xiaoxia Zuo

doi:10.1093/rheumatology/kez085

Global analysis of protein expression in muscle tissues of dermatomyositis/polymyosisits patients demonstrated an association between dysferlin and human leucocyte antigen A

Rheumatology (Oxford). 2019 Mar 25:kez085. doi: 10.1093/rheumatology/kez085. Online ahead of print.

Authors

Yizhi Xiao^{1

2}, Honglin Zhu^{1

2}, Liya Li^{1

2}, Siming Gao^{1

2}, Di Liu^{1

2}, Bingying Dai^{1

2}, Qiuxiang Li³, Huiqian Duan³, Huan Yang³, Quanzhen Li⁴, Huali Zhang⁵, Hui Luo^{1

2}, Xiaoxia Zuo^{1

2}

Affiliations

¹ Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China.
² Institute of Rheumatology and Immunology, Central South University, Changsha, China.
³ Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁵ Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China.

PMID: 30907425
DOI: 10.1093/rheumatology/kez085

Abstract

Objectives: DM and PM are characterized by myofibre damage with inflammatory cell infiltration due to the strong expressions of MHC class I HLA-A and monocyte chemoattractant protein-1 (MCP-1). Dysferlin (DYSF) is a transmembrane glycoprotein that anchors in the sarcolemma of myofibres. DYSF mutation is closely associated with inherited myopathies. This study aimed to determine the role of DYSF in the development of DM/PM.

Methods: Mass spectrometry was performed in muscle tissues from DM/PM patients and controls. The DYSF levels in muscle tissue, peripheral blood cells and serum were detected by Western blotting, IF, flow cytometry or ELISA. Double IF and co-immunoprecipitation were used to investigate the relationship between DYSF and HLA-A.

Results: Mass spectrometry and bioinformatics analysis findings suggested the dysregulated proteins in DM/PM patients participated in common biological processes and pathways, such as the generation of precursor metabolites and energy. DYSF was upregulated in the muscle tissue and serum of DM/PM patients. DYSF was mainly expressed in myofibres and co-localized with HLA-A and MCP-1. DYSF and HLA-A expressions were elevated in myocytes and endothelial cells after being stimulated by patient serum and IFN-β. However, no direct interactions were found between DYSF and HLA-A by co-immunoprecipitation.

Conclusion: Our study revealed the dysregulated proteins involved in common and specific biological processes in DM/PM patient samples. DYSF is upregulated and exhibits a potential role along with that of HLA-A and MCP-1 in inflammatory cell infiltration and muscle damage during the development of DM/PM.

Keywords: DYSF; HLA-A; dermatomyositis; polymyositis; protein profiles.