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06 March 2020 : Clinical Research  

The Association Between MUC5B Mutations and Clinical Outcome in Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Retrospective Exploratory Study in China

Na Wang1BE, Qian Zhang1B, Xiaoyan Jing1B, Jian Guo1CF, Hui Huang1DF, Zuojun Xu1AEG*

DOI: 10.12659/MSM.920137

Med Sci Monit 2020; 26:e920137

Abstract

BACKGROUND: Patients with rheumatoid arthritis (RA) who develop interstitial lung disease (RA-ILD), show features of usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT). This retrospective exploratory clinical study aimed to investigate the association between mutations in the MUC5B gene and clinical outcome in patients with RA, with or without RA-ILD, using whole-exome sequencing (WES).

MATERIAL AND METHODS: WES was performed using peripheral blood samples for mutations in the MUC5B gene in 51 patients diagnosed with RA without ILD, and 45 patients with RA-ILD. The cumulative incidence in acute exacerbations of RA-ILD and variables associated with acute exacerbations of RA-ILD were analyzed.

RESULTS: In patients with RA-ILD, the main genetic variants of MUC5B were identified, with an odds ratio (OR) of 3.410 (p=0.013). Nine patients with RA without ILD (17.6%) and 19 patients with RA-ILD (42.2%) expressed MUC5B variants. Patients with RA-ILD carrying MUC5B variants had a significantly increased duration of RA-ILD (p=0.03) and showed a UIP pattern on lung HRCT (p=0.01). Acute exacerbations of RA-ILD occurred in 25 patients during follow-up, including 13 patients with mutant MUC5B and 12 patients with wildtype MUC5B. Univariate analysis showed that MUC5B mutations (p=0.043), older age of onset of RA (p=0.041), increased serum anti-citrullinated protein antibodies (ACPAs) (p=0.033), and a UIP imaging pattern on HRCT (p=0.015) were significantly correlated with acute exacerbations of RA-ILD. However, these findings were not supported by multivariate analysis (p=0.065).

CONCLUSIONS: The carrier status of MUC5B variants was an indicator of reduced prognosis and increased exacerbations of RA-ILD.

Keywords: Arthritis, Juvenile, Lung Diseases, Interstitial, Mucin-5B, Age of Onset, Arthritis, Rheumatoid, DNA Mutational Analysis, Follow-Up Studies, Heterozygote, idiopathic pulmonary fibrosis, Lung, Mutation, Risk Factors, Symptom Flare Up, Tomography, X-Ray Computed, Whole Exome Sequencing

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750