Abstract
MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.
Similar content being viewed by others
Introduction
Mucins are components of mucus secretions with a crucial implication in the host defence against bacterial and fungal infections1. Mucin 5B is a gel-forming mucin and a major constituent of mucus in the respiratory tract2 that is encoded by MUC5B3. A common gain-of-function variant located in the promoter of this gene, MUC5B rs35705950, is described as the strongest genetic risk factor for the development of idiopathic pulmonary fibrosis (IPF)4, the most common and pernicious form of interstitial lung disease (ILD)5. A recent study performed by Juge et al. has revealed that MUC5B rs35705950 also significantly contributes to the risk of ILD amongst patients with rheumatoid arthritis (RA-ILD)6. In addition, MUC5B rs35705950 has been previously associated with chronic hypersensitivity pneumonitis (CHP), a relevant finding reported by Ley et al.7.
Antisynthetase syndrome (ASSD) is a connective tissue disease characterized by the typical clinical triad of arthritis, myositis and ILD8,9,10,11,12,13. Amongst these clinical features, ILD has been identified as the most frequent14 and severe15 manifestation of ASSD, with an incidence of approximately 80–90%16,17. The type and severity of ILD defines the long-term outcome of ASSD10, being the major determinant of morbidity and mortality in patients affected with this condition10,17,18,19,20,21,22. The pathophysiology of ASSD is not entirely understood, although some pieces of evidence support the hypothesis that both genetic and environmental factors may play a relevant role23.
Taking all these considerations into account, we aimed to determine whether the MUC5B rs35705950 promoter polymorphism, associated with IPF4, RA-ILD6 and CH7, was also implicated in the pathogenesis of ASSD. For this purpose, we took advantage of data from one of the largest cohorts of patients with ASSD.
Patients and Methods
Patients and study protocol
A total of 160 unrelated Spanish patients of European ancestry (self-reported) diagnosed with ASSD were enrolled in this study. Centres involved in the recruitment of these patients included Hospital Universitario Marqués de Valdecilla (Santander), Hospital Universitario San Cecilio (Granada), Hospital Clínico Universitario de Santiago (Santiago de Compostela), Hospital Universitario Araba (Vitoria), Hospital Clínico de Barcelona, Hospital Universitario de Bellvitge and Hospital Universitario Valle de Hebrón (Barcelona), and Hospital General Universitario Gregorio Marañón, Hospital Universitario Fundación Jiménez Díaz, Hospital Universitario La Paz and Hospital Universitario de la Princesa (Madrid). Patients were recruited if they had an antisynthetase antibody testing positive in at least two determinations along with one or more findings of the typical clinical triad (arthritis, myositis and/or ILD). Briefly, arthritis occurrence and its presentation pattern were clinically assessed by the referent physician; myositis was defined in case of muscle enzyme elevation (creatinine phosphokinase and/or aldolase) and the presence of typical electromyography alterations and/or compatible muscle biopsy findings and/or compatible muscle magnetic resonance; ILD was defined instrumentally by a restrictive pulmonary function test pattern [forced vital capacity (FVC) ≤ 80%, forced expiratory volume in one second (FEV1)/FVC ≥ 70%, decreased/normal FEV1, and/or diffusing capacity of the lung for carbon monoxide (DLCO) reduction >20%] and/or by the identification of alveolitis/fibrosis signs at high-resolution computed tomography of the lungs8,9,12,24,25. According to these criteria, 142 (88.8%) patients developed ILD associated with ASSD (ASSD-ILD+). Among them, 70% showed a non-specific interstitial pneumonia (NSIP) pattern in the high-resolution computed tomography (HRCT) images of the chest, while 19% of the patients showed a usual interstitial pneumonia (UIP) pattern. The remaining 11% of the ASSD-ILD+ patients presented other patterns. The occurrence of accompanying features, including fever, Raynaud´s phenomenon and mechanic’s hands, were also assessed as previously described11,18. Fever was considered in case of a body temperature ≥38 °C for more than 10 days without evidence of any other reason. Raynaud’s phenomenon was determined as the occurrence of a transient finger ischemia after cold exposure. Mechanic’s hands were defined as the occurrence of a thickened, hyperkeratotic, and fissured aspect of the radial sides of the fingers of the hands, in absence of other causes12,19. A detailed description of the main demographic and clinical information of the patients with ASSD enrolled in this study is displayed in Table 1.
In addition, a set of 232 ethnically matched (self-reported) patients diagnosed with ILD unrelated to ASSD was also included in this work. Centres involved in the recruitment of these patients included Hospital Universitario Marqués de Valdecilla (Santander), and Hospital Universitario Puerta de Hierro and Hospital Universitario 12 de Octubre (Madrid). Amongst these patients, 161 (69.4%) exhibited IPF, according to the classification criteria for the disease26, whereas 27 (11.6%) experienced RA-ILD and 44 (19.0%) exhibited CHP.
Moreover, a total of 534 ethnically (self-reported) matched unaffected control subjects, without history of any autoimmune or pulmonary disease, constituted by blood donors from Hospital Universitario Marqués de Valdecilla (Santander) and National DNA Bank Repository (Salamanca), was also enrolled in the study.
All patients and healthy controls signed an informed written consent before being included in the study, according to the declaration of Helsinki. The procedures followed were in accordance with the ethical standards of the approved guidelines and regulations, according to the Declaration of Helsinki. All experimental protocols were approved by the Ethics Committees of clinical research of Cantabria for Hospital Universitario Marqués de Valdecilla in Santander, of Andalucía for Hospital Universitario San Cecilio in Granada, of Galicia for Hospital Clínico Universitario de Santiago in Santiago de Compostela, of País Vasco for Hospital Universitario Araba in Vitoria, of Cataluña for Hospital Clínico de Barcelona, Hospital Universitario de Bellvitge and Hospital Universitario Valle de Hebrón in Barcelona, and of Madrid for Hospital General Universitario Gregorio Marañón, Hospital Universitario Fundación Jiménez Díaz, Hospital Universitario La Paz, Hospital Universitario de la Princesa, Hospital Universitario Puerta de Hierro and Hospital Universitario 12 de Octubre in Madrid.
Single nucleotide polymorphism selection and genotyping
The common gain-of-function genetic variant MUC5B rs35705950 (G/T), described as the strongest risk factor for IPF4 that also contributes to the risk of RA-ILD6, was selected in this study.
Genomic deoxyribonucleic acid from patients with ASSD, patients with ILD unrelated to ASSD and healthy controls was extracted from peripheral blood using standard procedures. All patients and healthy controls were genotyped for the MUC5B polymorphism mentioned above using a predesigned TaqMan 5′ single-nucleotide polymorphism genotyping assay (C_1582254_20) in a QuantStudioTM 7 Flex Real-Time polymerase chain reaction system, according to the conditions recommended by the manufacturer (Applied Biosystems, Foster City, CA, USA).
Negative controls and duplicate samples were included to check the accuracy of the genotyping.
Statistical analysis
Genotype data were checked for deviation from Hardy-Weinberg equilibrium (HWE) by chi-square test.
Both genotype and allele frequencies of MUC5B rs35705950 were calculated and compared between ASSD-ILD+ patients and healthy controls, patients with ASSD stratified according to specific clinical features of the disease (presence/absence of anti Jo-1 antibodies or ILD), ASSD-ILD+ patients stratified according to the presence of an UIP and non-UIP HRCT pattern, as well as between ASSD-ILD+ patients and those with ILD unrelated to ASSD.
To test for association, 3 × 2 and 2 × 2 contingency tables as well as chi-square test and/or Fisher´s exact test, when appropriate, were used. Strength of associations were estimated using odds ratios and 95% confidence intervals. P-values lower than 0.05 were considered as statistically significant.
All analyses were performed with STATA statistical software 12/SE (Stata Corp., College Station, TX, USA).
Results
The genotyping success rate was greater than 99%.
No evidence of departure from HWE was observed in healthy controls at the 5% significance level. Genotype and allele frequencies of MUC5B rs35705950 in healthy controls were similar to those reported for populations of European origin in the 1000 Genomes Project (http://www.internationalgenome.org/).
Differences in genotype and allele frequencies of MUC5B rs35705950 between ASSD-ILD+patients and healthy controls
Firstly, we compared genotype and allele frequencies of MUC5B rs35705950 between ASSD-ILD+ patients and healthy controls.
As shown in Table 2, no statistically significant differences in the genotype frequencies of MUC5B rs35705950 were disclosed when ASSD-ILD+ patients were compared to healthy controls. Likewise, allele frequencies of MUC5B rs35705950 did not significantly differ between ASSD-ILD+ patients and healthy controls (Table 2).
Differences in genotype and allele frequencies of MUC5B rs35705950 between patients with ASSD stratified according to specific clinical features of the disease
In a further step, we analysed potential differences in the genotype and allele frequencies of MUC5B rs35705950 between patients with ASSD stratified according to the presence/absence of anti Jo-1 antibodies or ILD.
No genotype or allele differences in MUC5B rs35705950 were observed when patients with ASSD were stratified according to the presence/absence of anti Jo-1 antibodies (Table 3). It was also the case when patients with ASSD who developed ILD were compared to those who did not exhibit this pulmonary complication (Table 3).
Differences in genotype and allele frequencies of MUC5B rs35705950 between ASSD-ILD+ patients stratified according to the presence of an UIP and non-UIP HRCT pattern”
Moreover, we also evaluated potential differences in the genotype and allele frequencies of MUC5B rs35705950 between ASSD-ILD+ patients stratified according to the presence of an UIP and non-UIP HRCT pattern.
No genotype or allele differences in MUC5B rs35705950 were observed in ASSD-ILD+ patients with an UIP pattern when compared to those with a non-UIP pattern (Table 4).
Differences in genotype and allele frequencies of MUC5Brs35705950 between ASSD-ILD+ patients and patients with ILD unrelated to ASSD
We also examined whether genotype or allele frequencies of MUC5B rs35705950 differed between patients with ASSD-ILD+ and those with ILD unrelated to ASSD.
Interestingly, we disclosed a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in patients with ASSD-ILD + compared to the whole cohort of patients with ILD unrelated to ASSD (GT: 19.7% versus 53.4%, p < 0.0001; TT: 0.7% versus 9.1%, p < 0.0001; T: 10.6% versus 35.8%, p < 0.0001) (Supplementary Table 1). This significant decrease was also observed when patients with ASSD-ILD + were compared to those with IPF (GT: 19.7% versus 58.8%, p < 0.0001; TT: 0.7% versus 6.9%, p < 0.0001; T: 10.6% versus 36.0%, p < 0.0001), RA-ILD (GT: 19.7% versus 40.7%, p = 0.006; TT: 0.7% versus 11.1%, p = 0.0001; T: 10.6% versus 31.5% p < 0.0001) and CHP (GT: 19.7% versus 43.2%, p = 0.0001; TT: 0.7% versus 15.9%, p < 0.0001; T: 10.6% versus 37.5% p < 0.0001 (Supplementary Table 1).
Discussion
Pathogenic similarities amongst diseases linked to ILD have been identified5,27. In this regard, an excess of mutations in genes previously associated with IPF has recently been detected in RA-ILD28, raising the question of whether a common genetic background underlies ILD related entities.
Taking into account these considerations, we aimed to evaluate for the first time the potential implication of MUC5B rs35705950 polymorphism, associated with IPF4, RA-ILD6 and CHP7, in the pathogenesis of ASSD, a disease characterised by a high ILD incidence. Our results showed no influence of this genetic variant in the susceptibility to ASSD. Furthermore, no specific association of MUC5B rs35705950 with clinical features of ASSD was observed in our study, indicating that this polymorphism does not represent a risk factor for the severity of the disease, and especially for ASSD-ILD+ patients. Additionally, no significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with an UIP pattern when compared to those with a non-UIP pattern. Interestingly, statistically significant differences in MUC5B rs35705950 frequencies between ASSD-ILD+ patients and those with ILD unrelated to ASSD (particularly IPF, RA-ILD and CHP) were found. This data suggests a different genetic predisposition between these conditions.
In keeping with our results in ASSD and unlike RA-ILD, no association of MUC5B rs35705950 with ILD in the setting of other connective tissue diseases was found. With respect to this, no influence of this genetic variant on myositis-ILD was disclosed whereas genetic differences regarding MUC5B rs35705950 between myositis-ILD and idiopathic ILD were also reported29. Likewise, lack of association between this genetic variant and ILD in the context of sarcoidosis30 and systemic sclerosis30,31 was described while differences in MUC5B rs35705950 frequencies were found when patients with sarcoidosis-ILD30 and those with systemic sclerosis-ILD30,31 were compared to patients with IPF.
Despite parallelisms amongst the different phenotypes of ILD, many clinical and radiological differences have been established5,27,32. In this regard, a NSIP pattern is more commonly found in ASSD and most connective tissue diseases-related ILD5,33, whereas a pattern of UIP is more frequently observed in patients with IPF and RA-ILD28. Because of that, it is possible that MUC5B rs35705950 may modulate phenotype differences amongst these conditions, suggesting that this genetic variant is not related to shared fibrotic mechanisms across diseases related to ILD, but is instead associated with an IPF and RA-ILD specific pathway. A potential bias may exist in our study regarding the fact that declarative data on the European ancestry were collected from patients and controls included.
In summary, our study does not support a role of MUC5B rs35705950 in ASSD pathogenesis. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.
References
Thornton, D. J., Rousseau, K. & McGuckin, M. A. Structure and function of the polymeric mucins in airways mucus. Annu. Rev. Physiol. 70, 459–486 (2008).
Thornton, D. J., Devine, P. L., Hanski, C., Howard, M. & Sheehan, J. K. Identification of two major populations of mucins in respiratory secretions. Am. J. Respir. Crit. Care Med. 150, 823–832 (1994).
Boucher, R. C. Muco-Obstructive Lung Diseases. N. Engl. J. Med. 380, 1941–1953 (2019).
Seibold, M. A. et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N. Engl. J. Med. 364, 1503–1512 (2011).
Cottin, V. et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur. Respir. Rev. 27, pii: 180076 (2018).
Juge, P. A. et al. MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease. N. Engl. J. Med. 379, 2209–2219 (2018).
Ley, B. et al. The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis. Lancet Respir. Med. 5, 639–647 (2017).
Cavagna, L. et al. Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome: Results From an International Retrospective Multicenter Study. Med. 94, e1144 (2015).
Cavagna, L. et al. Serum Jo-1 Autoantibody and Isolated Arthritis in the Antisynthetase Syndrome: Review of the Literature and Report of the Experience of AENEAS Collaborative Group. Clin. Rev. Allergy Immunol. 52, 71–80 (2017).
Chatterjee, S., Prayson, R. & Farver, C. Antisynthetase syndrome: not just an inflammatory myopathy. Cleve Clin. J. Med. 80, 655–666 (2013).
Dugar, M., Cox, S., Limaye, V., Blumbergs, P. & Roberts-Thomson, P. J. Clinical heterogeneity and prognostic features of South Australian patients with anti-synthetase autoantibodies. Intern. Med. J. 41, 674–679 (2011).
Gonzalez-Gay, M. A. et al. Timing of onset affects arthritis presentation pattern in antisyntethase syndrome. Clin. Exp. Rheumatol. 36, 44–49 (2018).
Imbert-Masseau, A., Hamidou, M., Agard, C., Grolleau, J. Y. & Cherin, P. Antisynthetase syndrome. Jt. Bone Spine. 70, 161–168 (2003).
Marie, I. et al. Interstitial lung disease in anti-Jo-1 patients with antisynthetase syndrome. Arthritis Care Res. 65, 800–808 (2013).
Rojas-Serrano, J. et al. Prognostic factors in a cohort of antisynthetase syndrome (ASS): serologic profile is associated with mortality in patients with interstitial lung disease (ILD). Clin. Rheumatol. 34, 1563–1569 (2015).
Yousem, S. A., Gibson, K., Kaminski, N., Oddis, C. V. & Ascherman, D. P. The pulmonary histopathologic manifestations of the anti-Jo-1 tRNA synthetase syndrome. Mod. Pathol. 23, 874–880 (2010).
Aggarwal, R. et al. Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann. Rheum. Dis. 73, 227–232 (2014).
Chinoy, H. et al. In adult onset myositis, the presence of interstitial lung disease and myositis specific/associated antibodies are governed by HLA class II haplotype, rather than by myositis subtype. Arthritis Res Ther. 8, R13 (2006).
Bartoloni, E. et al. Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: Results from a multicenter, international and retrospective study. Autoimmun. Rev. 16, 253–257 (2017).
Cavagna, L., Prisco, E., Montecucco, C. & Caporali, R. Pulmonary arterial hypertension in antisynthetase syndrome: comment on the article by Chatterjee and Farver. Arthritis Care Res. 63, 633–634 (2011).
Hervier, B. & Benveniste, O. Clinical heterogeneity and outcomes of antisynthetase syndrome. Curr. Rheumatol. Rep. 15, 349 (2013).
Selva-O’Callaghan, A. et al. Polymyositis/dermatomyositis-associated lung disease: analysis of a series of 81 patients. Lupus 14, 534–542 (2005).
Mirrakhimov, A. E. Antisynthetase syndrome: a review of etiopathogenesis, diagnosis and management. Curr. Med. Chem. 22, 1963–1975 (2015).
Cavagna, L. et al. Cyclosporine in anti-Jo1-positive patients with corticosteroid-refractory interstitial lung disease. J. Rheumatol. 40, 484–492 (2013).
Sebastiani, M. et al. Nailfold Capillaroscopy Characteristics of Antisynthetase Syndrome and Possible Clinical Associations: Results of a Multicenter International Study. J. Rheumatol. 46, 279–284 (2019).
Travis, W. D. et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am. J. Respir. Crit. Care Med. 188, 733–748 (2013).
Kreuter, M., Walscher, J. & Behr, J. Antifibrotic drugs as treatment of nonidiopathic pulmonary fibrosis interstitial pneumonias: the time is now (?). Curr. Opin. Pulm. Med. 23, 418–425 (2017).
Juge, P. A. et al. Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis. Eur. Respir. J. 49, pii: 1602314 (2017).
Johnson, C. et al. Exploration of the MUC5B promoter variant and ILD risk in patients with autoimmune myositis. Respir. Med. 130, 52–54 (2017).
Stock, C. J. et al. Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis. Thorax. 68, 436–441 (2013).
Borie, R. et al. The MUC5B variant is associated with idiopathic pulmonary fibrosis but not with systemic sclerosis interstitial lung disease in the European Caucasian population. PLoS one. 8, e70621 (2013).
Wells, A. U. et al. Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone cryptogenic fibrosing alveolitis. Am. J. Respir. Crit. Care Med. 149, 1583–1590 (1994).
Cottin, V. Idiopathic interstitial pneumonias with connective tissue diseases features: A review. Respirology. 21, 245–258 (2016).
Acknowledgements
We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was partially supported by grants from the Foundation for Research in Rheumatology (FOREUM). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ‘Instituto de Salud Carlos III’ (ISCIII), co-funded by the European Social Fund (ESF, ‘Investing in your future’) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009), co-funded by the European Regional Development Fund (ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ESF). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF). OG is Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). OG,is member of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. The work of OG (PI17/00409), was funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10.
Author information
Authors and Affiliations
Contributions
R.L.-M., S.R.-M. and F.G. carried out genotyping, participated in the design of the study, data analysis and helped to draft the manuscript. V.P.-C., V.M. and L.L.-G. have been involved in the acquisition, interpretation of data and coordination and helped to draft the manuscript. S.M.F.R., D.I.F., V.M.M.C., N.O.-C., N.P.G., A.M.-V., J.M.-B., F.J.L.-L., M.P.U., R.L., V.P., A.P.G., M.A.A.G., J.C.-A., F.R.-B., O.S.-P., L.N., G.B., A.B., F.H.-G., I.G., S.P.-G., J.N., E.T.-A., A.S.-O. and S.C. have been involved in the recruitment of patients, interpretation of data and coordination and helped to draft the manuscript. J.L. carried out the analysis and interpretation of the data and has been involved in revising the manuscript critically for important intellectual content. O.G. and L.C. have been involved in the interpretation of data and coordination and helped to draft the manuscript. J.M.C. and M.A.G.-G. have made substantial contributions to conception and design of the study, acquisition of data, coordination and helped to draft the manuscript and gave final approval of the version to be published.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
López-Mejías, R., Remuzgo-Martínez, S., Genre, F. et al. Influence of MUC5B gene on antisynthetase syndrome. Sci Rep 10, 1415 (2020). https://doi.org/10.1038/s41598-020-58400-0
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-020-58400-0
This article is cited by
-
Unusual presentation of antisynthetase syndrome: a case series and review of the literature
Journal of Medical Case Reports (2023)
-
Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome
Scientific Reports (2021)
-
Connective Tissue Disease-Related Interstitial Lung Disease: Prevalence, Patterns, Predictors, Prognosis, and Treatment
Lung (2020)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
