MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

Juge, Pierre-Antoine; Solomon, Joshua J.; Moorsel, Coline H.M. van; Garofoli, Romain; Lee, Joyce; Louis-Sydney, Fabienne; Rojas-Serrano, Jorge; González-Pérez, Montserrat I.; Mejía, Mayra; Buendía-Roldán, Ivette; Falfán-Valencia, Ramcés; Ambrocio-Ortiz, Enrique; Manali, Effrosyni D.; Papiris, Spyros; Karageorgas, Theofanis; Boumpas, Dimitrios T.; Antoniou, K.; Sidiropoulos, Prodromos; Trachalaki, Athina; Vis, Joanne J. van der; Jamnitski, Anna; Grutters, Jan C.; Kannengiesser, Caroline; Borie, R.; Kawano-Dourado, Letícia; Wémeau-Stervinou, Lidwine; Flipo, René‐Marc; Nunès, Hilario; Uzunhan, Y.; Valeyre, Dominique; Saidenberg-Kermanac’h, Nathalie; Boissier, Marie‐Christophe; Richez, Christophe; Schaeverbeke, Thierry; Doyle, Tracy J.; Wolters, Paul J.; Debray, Marie‐Pierre; Boileau, Cathérine; Porcher, Raphaël; Schwartz, David A.; Crestani, Bruno; Dieudé, Philippe

doi:10.1016/j.semarthrit.2021.07.002

Cited by 19 publications

(20 citation statements)

References 41 publications

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“…The mortality associated with SSc, pSS, and DM with ILD is significantly higher than in CTDs without ILD ( 23 , 25 , 26 ). Although disease severity has been linked with SNPs in the promoter region of MUC5AC and MUC5B, which are the most abundant airway mucins ( 7 , 9 – 12 ), and MUC5AC protein levels in BALF ( 27 ), there have been no reports on the serum levels of MUC5AC and MUC5B in CTD-ILD patients.…”

Section: Discussionmentioning

confidence: 99%

“…CTD-ILD mainly includes rheumatoid arthritis associated ILD (RA-ILD), systemic sclerosis associated ILD (SSc-ILD), primary Sjögren’s syndrome associated ILD (pSS-ILD), and polymyositis/dermatomyositis associated ILD (PM/DM-ILD) ( 3 – 6 ). CTD-ILD is a more severe disease than CTD, as individuals with RA-ILD show a rate of mortality that is 2–10 times higher than RA patients without ILD ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

“…The pathophysiology of CTD-ILD is unclear but genetic factors are thought to play an essential role in its development ( 8 ). Previous studies have demonstrated a strong relationship between ILDs and single nucleotide polymorphisms (SNPs) in the promoter regions of mucin 5B (MUC5B) ( 7 , 9 – 11 ) and mucin 5AC (MUC5AC) ( 12 ). MUC5AC and MUC5B, which account for approximately 90% of the mucoproteins ( 13 ), play a crucial role in the respiratory mucosal defense arsenal.…”

Section: Introductionmentioning

confidence: 99%

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Serum MUC5AC protein levels are correlated with the development and severity of connective tissue disease-associated pulmonary interstitial lesions

Lin

Liu²,

Wang³

et al. 2022

Front. Immunol.

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Background: Mucin 5AC (MUC5AC) and mucin 5B (MUC5B) are the major components of airway mucins. The expression levels of MUC5AC and MUC5B are related to connective tissue disease-associated interstitial lung disease (CTD-ILD) in the promoter region of MUC5AC and MUC5B and the relevant bronchoalveolar lavage fluid. However, the serum protein levels of MUC5AC and MUC5B have not been tested in CTD-ILD patients. In this study, we tested the serum levels of MUC5AC and MUC5B proteins in CTD-ILD patients and assessed their relationship with the occurrence and development of ILD.Methods: Serum samples were obtained from 168 CTD and 80 healthy participants from the First Affiliated Hospital of Xiamen University. The serum levels of MUC5AC and MUC5B proteins were measured by enzyme-linked immunosorbent assay.Results: Of the 168 individuals with CTD, 70 had primary Sjögren's syndrome (pSS), 64 had systemic sclerosis (SSc), and 34 had polymyositis/ dermatomyositis (PM/DM). There were 116 cases with concurrent ILD; ILD scores were 1 (n=23), 2 (n=41), and 3 (n=52). Serum MUC5AC and MUC5B protein levels were considerably higher in CTD-ILD than CTD-only individuals or healthy controls (both p<0.005). Among the CTD subgroups, MUC5AC was higher in individuals with concurrent ILD than in those without ILD (all p<0.05). MUC5AC was positively correlated with ILD severity in all three CTD subgroups (all R>0.47 and all p<0.05). The MUC5B levels varied substantially between SSc Frontiers in Immunology frontiersin.org 01

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Serum MUC5AC protein levels are correlated with the development and severity of connective tissue disease-associated pulmonary interstitial lesions

Lin

Liu²,

Wang³

et al. 2022

Front. Immunol.

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“…The expression levels of MUC4 and MUC16 were elevated in patients with IPF, with evidence for each MUC4 and MUC16 promoting the fibrotic process in collaboration with TGF-β ( 206 – 209 ). Of particular prominence is a strong association of a gain-of-function MUC5B gene promoter variant (rs35705950) with pulmonary fibrosis ( 210 – 215 ). To date, the MUC5B rs35705950 SNP remains the strongest and most reproducible risk factor for development of IPF.…”

Section: Neus and Mucs In Pulmonary Fibrosismentioning

confidence: 99%

“…A greater number of RA patients expressed MUC3 protein in synovial lining cells and synovial macrophages compared with normal controls ( 354 ). The MUC5B gene promoter variant rs5705950 was linked to an increased susceptibility to pulmonary fibrosis in RA patients ( 213 , 215 , 355 ). Increased salivary MUC7 sulfation was detected in RA patients compared with healthy controls ( 356 ).…”

Section: Neus and Mucs In Autoimmune Diseasesmentioning

confidence: 99%

Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond

2022

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Mammalian neuraminidases (NEUs), also known as sialidases, are enzymes that cleave off the terminal neuraminic, or sialic, acid resides from the carbohydrate moieties of glycolipids and glycoproteins. A rapidly growing body of literature indicates that in addition to their metabolic functions, NEUs also regulate the activity of their glycoprotein targets. The simple post-translational modification of NEU protein targets—removal of the highly electronegative sialic acid—affects protein folding, alters protein interactions with their ligands, and exposes or covers proteolytic sites. Through such effects, NEUs regulate the downstream processes in which their glycoprotein targets participate. A major target of desialylation by NEUs are mucins (MUCs), and such post-translational modification contributes to regulation of disease processes. In this review, we focus on the regulatory roles of NEU-modified MUCs as coordinators of disease pathogenesis in fibrotic, inflammatory, infectious, and autoimmune diseases. Special attention is placed on the most abundant and best studied NEU1, and its recently discovered important target, mucin-1 (MUC1). The role of the NEU1 - MUC1 axis in disease pathogenesis is discussed, along with regulatory contributions from other MUCs and other pathophysiologically important NEU targets.

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Extracting forced vital capacity from the electronic health record through natural language processing in rheumatoid arthritis‐associated interstitial lung disease

England,

Roul,

Yang

et al. 2023

Pharmacoepidemiology and Drug

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PurposeTo develop a natural language processing (NLP) tool to extract forced vital capacity (FVC) values from electronic health record (EHR) notes in patients with rheumatoid arthritis‐interstitial lung disease (RA‐ILD).MethodsWe selected RA‐ILD patients (n = 7485) in the Veterans Health Administration (VA) between 2000 and 2020 using validated ICD‐9/10 codes. We identified numeric values in proximity to FVC string patterns from clinical notes in the EHR. Subsequently, we performed processing steps to account for variability in note structure, related pulmonary function test (PFT) output, and values copied across notes, then assigned dates from linked administrative procedure records. NLP‐derived FVC values were compared to values recorded directly from PFT equipment available on a subset of patients.ResultsWe identified 5911 FVC values (n = 1844 patients) from PFT equipment and 15 383 values (n = 4982 patients) by NLP. Among 2610 date‐matched FVC values from NLP and PFT equipment, 95.8% of values were within 5% predicted. The mean (SD) difference was 0.09% (5.9), and values strongly correlated (r = 0.94, p < 0.001), with a precision of 0.87 (95% CI 0.86, 0.88). NLP captured more patients with longitudinal FVC values (n = 3069 vs. n = 1164). Mean (SD) change in FVC %‐predicted per year was similar between sources (−1.5 [30.0] NLP vs. −0.9 [16.6] PFT equipment; standardized response mean = 0.05 for both).ConclusionsNLP of EHR notes increases the capture of accurate, longitudinal FVC values by three‐fold over PFT equipment. Use of this NLP tool can facilitate pharmacoepidemiologic research in RA‐ILD and other lung diseases by capturing this critical measure of disease severity.

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MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

Cited by 19 publications

References 41 publications

Serum MUC5AC protein levels are correlated with the development and severity of connective tissue disease-associated pulmonary interstitial lesions

Serum MUC5AC protein levels are correlated with the development and severity of connective tissue disease-associated pulmonary interstitial lesions

Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond

Extracting forced vital capacity from the electronic health record through natural language processing in rheumatoid arthritis‐associated interstitial lung disease

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