scholarly journals AB0007 Shared genetic predisposition in rheumatoid arthritis–interstitial lung disease and familial pulmonary fibrosis

2017 ◽  
Author(s):  
PA Juge ◽  
R Borie ◽  
C Kannengiesser ◽  
S Gazal ◽  
P Revy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Genetic Predisposition ◽  
Shared Genetic ◽  
Familial Pulmonary Fibrosis

scholarly journals Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis

2017 ◽  
Vol 49 (5) ◽  
pp. 1602314 ◽  
Author(s):  
Pierre-Antoine Juge ◽  
Raphaël Borie ◽  
Caroline Kannengiesser ◽  
Steven Gazal ◽  
Patrick Revy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
European Ancestry ◽  
Whole Exome ◽  
Burden Test ◽  
Excess Number ◽  
Familial Pulmonary Fibrosis

Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53–6.12; p=9.45×10−4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10−2).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.

scholarly journals SAT0098 TREATMENT OF A COHORT OF PATIENTS WITH INTERSTITIAL LUNG DISEASE AND RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 982.2-982
Author(s):  
C. Aguilera Cros ◽  
M. Gomez Vargas ◽  
R. J. Gil Velez ◽  
J. A. Rodriguez Portal
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Latin American ◽  
Usual Interstitial Pneumonia ◽  
Specific Treatment ◽  
American Thoracic Society ◽  
Rapid Progression

Background:There is no specific treatment for interstitial lung disease (ILD) secondary to Rheumatoid Arthritis (RA) other than the treatment of RA without extra-articular involvement. Current regimens usually include corticosteroid therapy with or without immunosuppressants (IS), there is no consensus for the treatment.Objectives:To analyze the different treatment regimens in a cohort of patients with ILD and RA in our clinical practice.Methods:Descriptive study of 57 patients treated in our Hospital (1/1/2018 until 12/31/2019) with a diagnosis of RA (ACR 2010 criteria) and secondary ILD.The most recent American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines define three HRCT (High Resolution Computed Tomography) patterns of fibrosing lung disease in the setting of idiopathic pulmonary fibrosis (IPF): definite Usual Interstitial pneumonia (UIP) (traction bronchiectasis and honeycombing), possible UIP and inconsistent with UIP. The distinction between definite UIP and possible UIP in these to the presence or absence of honeycombing. Approved by the Ethics Committee.Quantitative variables are expressed as mean (SD) and dichotomous variables as percentages (%). Statistical analysis with SPSS version 21.Results:21 men and 36 women were included, with a mean age of 69 ± 10 years (mean ± SD), history of smoking (smokers 14%, non-smokers 43%, former smokers 42%). Clinical ILD at diagnosis (dyspnea 61%, dry cough 56%, crackling 70%, acropachy 7%). 84% were positive rheumatoid factor and 70% positive anticitrullinated protein antibody.Diagnosis of ILD by HRCT in 100% of patients with different patterns: defined UIP 26 (45%), probable UIP 2 (3%) and not UIP 29 (50%). The diagnosis of ILD was confirmed by biopsy in 12 patients.79% underwent (T) treatment prior to the diagnosis of ILD with glucocorticoids and disease-modifying drugs (DMARD). Among the traditional DMARDs used were: Methotrexate 68% (there were no cases of MTX pneumonitis), Leflunomide 47%, Hydroxychloroquine 26% and Sulfasalazine 21%. Biological therapy in 15 patients: Etanercept 19%, Adalimumab 5%, Infliximab 3% and Certolizumab 2%. Two patients presented an exacerbation and rapid progression of the ILD during the T with Etanercept with the final result of death.T with IS after the diagnosis of ILD in 80% of patients (Azathioprine 15, Rituximab 14, Abatacept 10, Tocilizumab 4, Sarilumab 1, Mofetil mycophenolate 1 and Cyclophosphamide 1).Two patients with defined UIP perform T with antifibrotic: 1st Nintedanib (INBUILD Trial, This article was published on September 29, 2019, at NEJM.org) 2nd Pirfenidone (initial diagnosis of IPF Idiopathic Pulmonary Fibrosis and subsequent of seropositive RA with UIP). Both improved greater than 10% in forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) in the 6 months after onset of T.Conclusion:Our results, in general, agree with what is published in the literature. Prospective, multicentre and larger sample studies are necessary to better define which patients would benefit more from IS T or antifibrotic T (or if the antifibrotic should be added to the previous IS).Disclosure of Interests:None declared

Comparative Profiling of Serum Protein Biomarkers in Rheumatoid Arthritis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 72 (3) ◽  
pp. 409-419 ◽  
Author(s):  
Daniel J. Kass ◽  
Mehdi Nouraie ◽  
Marilyn K. Glassberg ◽  
Nitya Ramreddy ◽  
Karen Fernandez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Serum Protein ◽  
Protein Biomarkers

scholarly journals Profibrotic effect of IL-17A and elevated IL-17RA in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated lung disease support a direct role for IL-17A/IL-17RA in human fibrotic interstitial lung disease

2019 ◽  
Vol 316 (3) ◽  
pp. L487-L497 ◽  
Author(s):  
Jie Zhang ◽  
Dan Wang ◽  
Lei Wang ◽  
Shaohua Wang ◽  
Anja C. Roden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
T Helper 17 ◽  
Direct Role ◽  
Lung Biopsies

Interleukin (IL)-17 is a T helper 17 cytokine implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Although IL-17A has a well-established role in murine pulmonary fibrosis models, its role in the tissue remodeling and fibrosis occurring in idiopathic pulmonary fibrosis (IPF) and RA-associated interstitial lung disease (RA-ILD) is not very well defined. To address this question, we utilized complimentary studies to determine responsiveness of human normal and pathogenic lung fibroblasts to IL-17A and used lung biopsies acquired from patients with IPF and RA-ILD to determine IL-17A receptor (IL-17RA) expression. Both normal and pathogenic IPF lung fibroblasts express functional IL-17RA and respond to IL-17A stimulation with cell proliferation, generation of extracellular matrix (ECM) proteins, and induction of myofibroblast transdifferentiation. Small interfering RNA (siRNA) silencing of IL-17RA attenuated this fibroblast response to IL-17A on ECM production. These fibroblast responses to IL-17A are dependent on NF-κB-mediated signaling. In addition, inhibiting Janus activated kinase (JAK) 2 by either siRNA or a selective pharmacological inhibitor, AZD1480—but not a JAK1/JAK3 selective inhibitor, tofacitinib—also significantly reduced this IL-17A-induced fibrogenic response. Lung biopsies of RA-ILD patients demonstrate significantly higher IL-17RA expression in areas of fibroblast accumulation and fibrosis, compared with either IPF or normal lung tissue. These observations support a direct role for IL-17A in lung fibrosis that may be particularly relevant in the context of RA-ILD.

SAT0070 LUNG ULTRASOUND IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THE DEFINITION OF SIGNIFICANT INTERSTITIAL LUNG DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 969.1-970
Author(s):  
M. DI Carlo ◽  
M. Tardella ◽  
E. Filippucci ◽  
F. Salaffi
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Roc Curve ◽  
Roc Curve Analysis ◽  
High Resolution Computed Tomography ◽  
The Mean ◽  
Sat 1 ◽  
B Lines

Background:In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. LUS allows the detection of artifacts (B-lines) characteristic of ILD, without the need to use ionizing radiation. However, it is not yet well defined how to interpret the LUS findings under suspicion of RA-ILD.Objectives:To determine the cut-off number of LUS B-lines that identifies a significant RA-ILD.Methods:A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence.Patients underwent LUS, chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of HRCT using a computer-aided method (CaM). The 10% of fibrosis, measured with this method, was considered as a cut-off for the presence of significant RA-ILD. The LUS was carried out in 14 defined intercostal spaces using a linear multifrequency probe 6-18 MHz (MyLab Class C, Esaote S.p.A., Genoa, Italy) and the number of B-lines present in each intercostal space was counted and summed up (Figure 1). The discriminating validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Figure 1.LUS B-line illustrative.Results:72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years), a mean ACPA titre of 327.6 (SD 633.3) U/ml and a rheumatoid factor of 324.6 (SD 748.7) U/ml. The mean estimate of pulmonary fibrosis using the CaM was 11.2% (SD 7.5) at HRCT, while at LUS the mean number of B-lines was 10.6 (SD 15.1). Pulmonary fibrosis of 10% as measured by the CaM at HRCT was detected in 25 patients (34.72%). Applying this HRCT cut-off point as an estimate of significant fibrosis, the presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant fibrosis with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4 (Figure 2).Figure 2.Area under the ROC curve to determine the number of B-lines at LUS to define a significant RA-ILD, applying the 10% of fibrosis at chest HRCT measured by OsiriX as external criterion.Conclusion:The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.References:[1] Tardella M, et al. Ultrasound B-lines in the evaluation of interstitial lung disease in patients with systemic sclerosis: Cut-off point definition for the presence of significant pulmonary fibrosis. Medicine (Baltimore). 2018;97(18):e0566.[2] Salaffi F, et al. High-resolution computed tomography of the lung in patients with rheumatoid arthritis: Prevalence of interstitial lung disease involvement and determinants of abnormalities. Medicine (Baltimore). 2019;98(38):e17088.Disclosure of Interests:Marco Di Carlo: None declared, Marika Tardella: None declared, Emilio Filippucci Speakers bureau: Dr. Filippucci reports personal fees from AbbVie, personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from Roche, personal fees from Union Chimique Belge Pharma, personal fees from Pfizer, outside the submitted work., Fausto Salaffi: None declared

scholarly journals Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease

2015 ◽  
Vol 9s1 ◽  
pp. CCRPM.S23289 ◽  
Author(s):  
Takafumi Suda
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Acute Exacerbation ◽  
Interstitial Pneumonia ◽  
Usual Interstitial Pneumonia ◽  
Cytotoxic Agents ◽  
Radiological Patterns

Pulmonary involvement is common in rheumatoid arthritis (RA) and affects all the components of the lung. Interstitial lung disease (ILD) is the most predominant pulmonary manifestation and has been identified as the main cause of morbidity and mortality in RA. Clinically significant RA-ILD occurs in approximately 10% of RA patients. Several risk factors, such as old age, male gender, and smoking, have been reported to date. Histologically, the proportion of the usual interstitial pneumonia (UIP) pattern is higher in RA-ILD than in ILD associated with other connective tissue diseases, and RA-ILD also shows nonspecific interstitial pneumonia and organizing pneumonia patterns. High-resolution computed tomography scans are highly predictive of the histological UIP pattern with a specificity of 96%-100%. Acute exacerbation, which is the acute deterioration of the respiratory status characterized by newly developed bilateral infiltrates with unknown etiologies, has been reported in RA-ILD. Although acute exacerbation of RA-ILD has high mortality, similar to that of idiopathic pulmonary fibrosis, its incidence is lower in RA-ILD than in idiopathic pulmonary fibrosis. A consensus treatment has not yet been established. Current therapeutic regimens typically include corticosteroids with or without cytotoxic agents. Recent large longitudinal studies reported that the prognosis of RA-ILD was poor with a median survival of 2.6-3.0 years. Furthermore, histological and/or radiological patterns, such as UIP or non-UIP, have significant prognostic implications. RA-ILD patients with histological or radiological UIP patterns have poorer prognoses than those with non-UIP patterns. This review assessed the characteristics of RA-ILD by overviewing recent studies in the field and focused on the clinical significance of histological and/or radiological patterns in RA-ILD.

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