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Calcinosis and malignancy are rare in Chinese adult patients with myositis and nuclear matrix protein 2 antibodies identified by an unlabeled immunoprecipitation assay

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Abstract

Autoantibodies in patients with myositis may associate with specific clinical manifestations. This study aimed to identify a subset of patients with myositis carrying antinuclear matrix protein 2 (anti-NXP-2) antibodies using an unlabeled immunoprecipitation (IP) assay, and clarify the features of these patients in a Chinese cohort. We developed novel methods for unlabeled protein IP and immunoblotting of Myc-tagged truncated NXP-2 fragments for anti-NXP-2 detection. The sera of 120 Chinese adult patients with myositis were screened for anti-NXP-2 by IP and immunoblot. Anti-NXP-2 antibodies were detected in 10 of the 120 patients (8.3%) using the established unlabeled protein IP and immunoblotting, with 70% (7/10) exhibiting either heliotrope rash or Gottron’s papules. All 10 anti-NXP-2-positive patients exhibited myopathy and 60% complained of dysphagia. Severe diffuse calcinosis (10%) and nasopharyngeal carcinoma (10%) were each only present in single anti-NXP-2-positive patients with myositis. Antibodies against Ro-52 were found in four living but not in three deceased anti-NXP-2-positive patients. A comprehensive review of 13 anti-NXP-2 studies demonstrated markedly lower anti-NXP-2 prevalence among adult patients with myositis and lower association of anti-NXP-2 with calcinosis in Japan, China, and Hungary than in the USA and Italy. Anti-NXP-2 antibody association with internal malignancy in adult patients varied from 0 to 50% across different studies. A novel IP assay was developed to detect patients with myositis expressing anti-NXP-2. Calcinosis and malignancy are rare in Chinese adult patients with myositis positive for anti-NXP-2. Literature review indicated highest anti-NXP-2 prevalence and association of anti-NXP-2 with calcinosis in US and Italian myositis cohorts.

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Acknowledgments

We acknowledge Guochun Wang from China-Japan Friendship Hospital, who kindly provided anti-NXP-2-positive sera.

Funding

This work was supported by the National Natural Science Foundation of China [grant numbers 81771765, 81771766, and 81471897] and the Clinical Research Fund of Xiangya Hospital Central South University (2014 L10).

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Author notes

  1. Li Wang and Li Huang contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, Xiangya Hospital of Central South University, Changsha City, 410078, Hunan, People’s Republic of China

    Li Wang, Li Huang, Yanjuan Liu, Yizhi Xiao, Hui Luo, Xiaoxia Zuo, Yisha Li & Huali Zhang

  2. Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha City, 410078, Hunan, People’s Republic of China

    Li Wang, Li Huang, Yang Yang, Huan Chen, Yanjuan Liu, Ke Liu, Meidong Liu, Yisha Li, Xianzhong Xiao & Huali Zhang

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  1. Li Wang
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Correspondence to Yisha Li, Xianzhong Xiao or Huali Zhang.

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The study is in accordance with the ethical principles of the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board at the Xiangya Hospital of Central South University (approval number: 201703567). All study participants provided written informed consent prior to participation in the study.

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Wang, L., Huang, L., Yang, Y. et al. Calcinosis and malignancy are rare in Chinese adult patients with myositis and nuclear matrix protein 2 antibodies identified by an unlabeled immunoprecipitation assay. Clin Rheumatol 37, 2731–2739 (2018). https://doi.org/10.1007/s10067-018-4216-x

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