2. Academic Validation
  3. The central helicase domain holds the major conformational epitopes of melanoma differentiation-associated gene 5 autoantibodies

The central helicase domain holds the major conformational epitopes of melanoma differentiation-associated gene 5 autoantibodies

  • Rheumatology (Oxford). 2023 Aug 8;kead397. doi: 10.1093/rheumatology/kead397.
Yongxin Mo 1,  Yan Ye 2,  Lisheng Peng 3,  Xiaobo Sun 3,  Xiaofen Zhong 1,  Rui Wu 4
Affiliations

Affiliations

  • 1 Department of Biotherapy Centre, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • 2 Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 3 Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
  • 4 Department of Rehabilitation, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
PMID: 37551942 DOI: 10.1093/rheumatology/kead397
Abstract

Objectives: Autoantibodies against MDA5 serve as a biomarker for dermatomyositis (DM) and a risk factor for interstitial lung disease (ILD). MDA5 is a protein responsible for sensing RNA virus Infection and activating signalling pathways against it. However, little is known about antigen epitopes on MDA5 autoantibodies. We aimed to determine the interaction of the MDA5 autoantibody-antigen epitope.

Methods: Cell-based assays (CBAs), immunoprecipitation-immunoblot assays, and various immunoblotting techniques were used in the study.

Results: We demonstrate that DM patient autoantibodies recognize MDA5 epitopes in a native conformation-dependent manner. Furthermore, we identified the central helicase domain formed by Hel1, Hel2i, Hel2, and pincer (3Hel) as the major epitopes. As proof of principle, the purified 3Hel efficiently absorbed MDA5 autoantibodies from patient sera through immunoprecipitation-immunoblot assay.

Conclusion: Our study uncovers the nature of antigen epitopes on MDA5 and provides guidance for diagnosis and targeted therapeutic approach development.

Keywords

MDA5; antigen; autoantibody; dermatomyositis; epitopes.

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