SAT0288 CHARACTERIZATION OF ANTI-AMINOACYL TRNA SYNTHETASE AUTOANTIBODIES IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1088.1-1089
Author(s):  
C. Preger ◽  
A. Notarnicola ◽  
C. Hellström ◽  
E. Wigren ◽  
C. Cerqueira ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Clinical Manifestations ◽  
Trna Synthetase ◽  
University Hospital ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Research Support ◽  
Mortality And Morbidity

Background:Idiopathic inflammatory myopathies (IIM) are rare chronic inflammatory diseases associated with high mortality and morbidity [1]. One sub-group of IIM, anti-synthetase syndrome (ASS), is characterized by the presence of autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS), together with specific clinical manifestations such as myositis, interstitial lung disease (ILD), arthritis, mechanic’s hand, Raynaud’s syndrome and fever [2]. The most common anti-aaRS autoantibody, anti-Jo1 targeting histidyl tRNA synthetase (HisRS), is present in up to 20-30% of patients with IIM, and up to 90% of patients with myositis and ILD [3, 4]. Besides Jo1, there are today seven other identified autoantigens within the aaRS family.Objectives:A large part of patients with IIM, including individuals with clinical manifestations indicating ASS, test seronegative to all known myositis specific autoantibodies. However, these patients could potentially harbor autoantibodies against targets not tested for in clinic. In this study, we aimed at extending the detection of autoantibodies by including all cytoplasmic aaRS in the analysis of patients with IIM. We hypothesized the existence of new potential autoantigens within this protein family.Methods:The presence of anti-aaRS autoantibodies was determined using a multiplex suspension bead array assay on 242 IIM patients from the Karolinska University Hospital myositis cohort. A panel of 186 recombinant constructs, representing 57 proteins that included full-length or partial sequence overlaps between constructs of all cytoplasmic aaRS as well as other myositis related proteins, were coupled to magnetic color-coded beads and each plasma sample was tested against the complete antigen panel.Results:By the use of this multiplex method we identified patients with autoantibodies against many of the tested aaRS. Autoantibodies binding to HisRS have previously been shown to bind with higher reactivity to the WHEP domain of HisRS and this was also confirmed in this study. We confirmed reactivity against three of the other aaRS tested for in the clinic (PL-12, PL-7, and EJ). In addition, we identified patients positive for anti-Zo, -KS and -HA, autoantibodies usually not screened for in routine. Finally, our data indicates that there are autoantibodies binding to other aaRS than the previously known eight autoantigens, which will be presented.Conclusion:In this study, we could detect autoantibodies in plasma from patients with IIM, both against the most common aaRS autoantigens, but also against other aaRS that are usually not tested for in clinic. We conclude that it is important to continue the studies of anti-aaRS autoantibodies, and their correlation to clinical manifestations, and in the long run also include more aaRS autoantigens in clinical practice.References:[1]Dobloug, G.C., et al., Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study. Ann Rheum Dis, 2018. 77(1): p. 40-47.[2]Barsotti, S. and I.E. Lundberg, Myositis an evolving spectrum of disease. Immunol Med, 2018. 41(2): p. 46-54.[3]Vencovsky, J., H. Alexanderson, and I.E. Lundberg, Idiopathic Inflammatory Myopathies. Rheum Dis Clin North Am, 2019. 45(4): p. 569-581.[4]Richards, T.J., et al., Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum, 2009. 60(7): p. 2183-92.Disclosure of Interests:Charlotta Preger: None declared, Antonella Notarnicola: None declared, Cecilia Hellström: None declared, Edvard Wigren: None declared, Catia Cerqueira: None declared, Peter Nilsson: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Helena Persson: None declared, Susanne Gräslund: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,

scholarly journals Series of clinical cases of patients with idiopathic inflammatory myopathy and interstitial lung disease from the registry of idiopathic inflammatory myopathies of the Argentine Society of Rheumatology

2020 ◽  
pp. 12-17
Author(s):  
Y.M. Ponce ◽  
M.M. Zalazar ◽  
A.D. García Coello ◽  
O.L. Rillo
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Clinical Manifestations ◽  
Idiopathic Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Disease Prognosis ◽  
Immune Mediated ◽  
Necrotizing Myositis

Idiopathic Inflammatory Myopathies (MII) are a heterogeneous group of diseases characterized by muscle weakness and inflammation underlying muscle biopsy. The main organs affected are muscle, skin and the lung can also be affected. They are distinguished within clinical subtypes such as Polymyositis (PM), Dermatomyositis (DM), DM with the variant Clinically Amiopathic Dermatomyositis (DMCA), the Syndrome Antisynthetase (SAS), Immune-mediated Necrotizing Myositis, Body Myositis Inclusion (MCI) and Neoplasia-Associated Myositis. The presence of certain specific and associated antibodies predisposes to the development of clinical manifestations, determining the disease prognosis. 4 patients from the Registry of MII of the Argentine Society of Rheumatology (SAR) are presented with these characteristics: one patient with PM and anti Jo-1 positive and three patients with DM (one with DMCA and anti-RO 52 and two patients with anti-PL7 and anti-TI-F1γ respectively).

scholarly journals Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110609
Author(s):  
Erin M. Wilfong ◽  
Rohit Aggarwal
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
The United States ◽  
Inflammatory Myopathies ◽  
Mortality And Morbidity ◽  
Randomized Controlled ◽  
Fda Approval

The antifibrotic therapies nintedanib and pirfenidone were first approved by the United States for the treatment of idiopathic pulmonary fibrosis in 2014. In 2020, nintedanib received U.S. Food and Drug Administration (FDA) approval for the treatment of all progressive fibrosing interstitial lung disease (ILD). Given that a major cause of mortality and morbidity in the idiopathic inflammatory myopathies (IIM) is progressive interstitial lung disease and respiratory failure, antifibrotic therapies may be useful as adjuvant to traditional immunosuppression. However, randomized controlled trials of antifibrotic therapies in IIM are lacking. The purpose of this review is to (1) summarize the mechanism of action of nintedanib and pirfenidone in ILD with possible role in IIM-ILD, (2) review the clinical data supporting their use in interstitial lung disease in general, and more specifically in connective tissue disease associated ILD, and (3) discuss the evidence and remaining challenges for using antifibrotic therapies in IIM-ILD.

scholarly journals Anti-melanoma-associated Antigen A1 Autoantibodies Predict the Outcome of Patients With Idiopathic Inflammatory Myopathies Related Interstitial Lung Disease

2020 ◽  
Author(s):  
Yawen Shen ◽  
Wei Jiang ◽  
Hanbo Yang ◽  
He Chen ◽  
Qinglin Peng ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lupus Erythematosus ◽  
Estimating Equation ◽  
Good Prognosis ◽  
Trna Synthetase ◽  
Fisher Exact Test ◽  
Idiopathic Inflammatory Myopathies ◽  
Disease Course ◽  
Inflammatory Myopathies

Abstract Background The discovery of novel autoantibody in patients with idiopathic inflammatory myopathies (IIMs) is of great significance for clinical subtype stratification and potential pathogenesis. Previous literatures have found that tumor-associated antigens were involved in the pathogenesis of IIM. Therefore, in this study, we aimed to explore the prevalence and clinical association of autoantibodies against melanoma-associated antigen A1 (MAGE-A1) in patients with IIM. Methods ELISA was performed to detect anti-MAGE-A1 autoantibodies in patients with IIM, systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren syndrome, systemic sclerosis, and healthy controls, and the results were confirmed using the dot-immunoblotting assay. The association between anti-MAGE-A1 autoantibody and clinical characteristics was analyzed in IIM patients. T test, Mann-Whitney U test, double-sided Pearson's Chi-square, Fisher exact test, Spearman correlation analysis as well as the generalized estimating equation were applied in the statistical analyses. Results Anti-MAGE-A1 autoantibodies were detected in 5.03% (29/576) of all IIM patients, 4.60% (18/390) of dermatomyositis, 7.20% (5/69) of amyopathic dermatomyositis, and 5.10% (6/117) of polymyositis/immune-mediated necrotizing myopathy patients. The frequency of interstitial lung disease (ILD) was higher in anti-MAGE-A1-positive patients than those in anti-MAGE-A1-negative ones (82.8% vs 55%, p = 0.003). Anti-MAGE-A1-positive patients with IIM associated ILD had less dyspnea, more commonly asymptomatic ILD, and higher percentage of force vital capacity and diffusing lung capacity of carbon monoxcide of predicted values when compared to negative ones. The anti-aminoacyl-tRNA synthetase (ARS) coexisting anti-MAGE-A1-positive patients had common monocyclic disease course, while only anti-ARS-positive and anti-ARS coexisting anti-Ro52-positive patients had a more polycyclic disease course. None of anti-ARS-positive patients coexisting anti-MAGE-A1 antibody died during 10-year follow-up evaluation. Conclusion Anti-MAGE-A1 is a novel autoantibody associated with ILD in IIM patients. Anti-MAGE-A1-positive IIM patients with ILD appear to have good prognosis. Detection of anti-MAGE-A1 autoantibody may be useful in predicting the outcome of IIM patients with ILD.

scholarly journals Biomarkers and Autoantibodies of Interstitial Lung Disease with Idiopathic Inflammatory Myopathies

2015 ◽  
Vol 9s1 ◽  
pp. CCRPM.S36748 ◽  
Author(s):  
Hajime Yoshifuji
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Trna Synthetase ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Aminoacyl Trna Synthetase ◽  
High Resolution Computed Tomography ◽  
Ground Glass Attenuation

Various autoantibodies are seen in idiopathic inflammatory myopathies. Among myositis-specific antibodies, anti-aminoacyl-tRNA synthetase and anti-melanoma differentiation-associated protein 5 (MDA5) antibodies are associated with interstitial lung disease (ILD). Anti-MDA5 antibodies are associated with dermatomyositis (DM) or clinically amyopathic DM complicated with rapidly progressive ILD. In anti-MDA5-positive patients, a random ground-glass attenuation pattern is a characteristic finding of ILD in chest high-resolution computed tomography. Conversely, anti-aminoacyl-tRNA synthetase antibodies are not associated with rapidly progressive ILD but with chronic ILD. DM or clinically amyopathic DM patients with anti-MDA5, and characteristic high-resolution computed tomography findings are highly likely to have devastating ILD and need aggressive treatment.

scholarly journals AB0614 METHOTREXATE DOESN’T LOWER THE RISK OF DEVELOPING INTERSTITIAL LUNG DISEASE IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES WITH JO-1 ANTIBODIES.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1603.1-1603
Author(s):  
P. Szczęsny ◽  
K. Swierkocka ◽  
A. Felis-Giemza ◽  
M. Olesińska
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Immunosuppressive Drugs ◽  
Trna Synthetase ◽  
Classification Criteria ◽  
Capital City ◽  
Mortality Factor ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
American College Of Rheumatology

Background:In patients with idiopathic inflammatory myopathies (IIM) most commonly found autoantibody against histidyl-tRNA synthetase (anti-Jo-1) is associated with development of interstitial lung disease (ILD), which has been recognized as a serious mortality factor.Objectives:To assess if methotrexate as an initial steroid sparing agent lowers the risk of developing ILD in anti-Jo-1 positive patients diagnosed with IIM.Methods:Medical records of IIM patients treated in a referral clinic in capital city of Poland between 2008 and 2018 were reviewed. Inclusion criteria were: fulfillment of ACR/EULAR 2017 classification criteria for IIM, positivity of anti-Jo-1 antibodies in the EUROLINE test, introduction of corticosteroids equivalent to ≥0,5mg of prednisone. Exclusion criteria: insufficient data on disease course, history of IIM <18 months.Results:29 patients were included for this analysis. ILD was present at the onset in 52% (n:15) patients. Other 14 patients were treated initially with corticosteroids ≥0,5mg/kg along with methotrexate up to 25mg/week. In all 14 patients methotrexate was well tolerated and led to successful reduction of steroid dose. However, ILD attributed to the primary disease appeared in follow up in 50%(n:7) of these patients (medium 36 months), which resulted in alteration of treatment. In 7 patients ILD didn’t develop.Conclusion:Our study shows that methotrexate in dose up to 25mg/week doesn’t lower the risk of developing ILD in Jo-1 positive IIM patients in the long term suggesting that other medication should be used as a first line treatment for this group.References:[1]Factors affecting survivorship in polymyositis: a life-table study of 124 patients. Medsger TA, Robinson H, Masi AT. Arthritis Rheum 1971;14:249–58[2](2018). Treatment of adult idiopathic inflammatory myopathies with conventional immunosuppressive drugs. Keyßer, G., Zierz, S., & Kornhuber, M. Z Rheumatol. 2019;78(2):183–189.[3]2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups Lundberg IE, Tjärnlund A, Bottai M, et al. Ann Rheum Dis. 2017;76(12):1955–1964.Disclosure of Interests:None declared

scholarly journals Idiopathic Inflammatory Myopathies (IIMs)

2021 ◽  
Vol 2 (1) ◽  
pp. 38-41
Author(s):  
Adel Ekladious ◽  
Keyword(s):  
Pulmonary Hypertension ◽  
Respiratory Failure ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Loss Of Weight ◽  
Pet Ct ◽  
Skin Signs

Diagnosis of inflammatory myopathy are usually based on clinical examination and histopathology of the muscles and muscle biopsy, usually guided by PET-CT. This is not uncommonly presented by extramacular signs like interstitial lung disease, dysphagia, few skin signs, loss of weight, arteritis, cardiomyopathy, Pulmonary hypertension, respiratory failure, and cancer.

scholarly journals SAT0306 SEMIQUANTITATIVE AND QUANTITATIVE ANALYSIS OF LUNG CT IN THE ASSESSMENT OF INTERSTITIAL LUNG DISEASE IN IDIOPATHIC INFLAMMATORY MYOPATHIES WITH A FOCUS ON ANTISYNTHETASE.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1098.2-1098
Author(s):  
S. Barsotti ◽  
C. Roncella ◽  
A. Valentini ◽  
L. Cavagna ◽  
R. Castellana ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Special Focus ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Increased Risk ◽  
Group 2 ◽  
Lung Ct ◽  
Group 1

Background:Interstitial lung disease (ILD), is common in patients with idiopathic inflammatory myopathies (IIM) and strongly impact on patients’ morbidity and mortality. Patients with anti-aminoacyl-transfer RNA-synthetases (anti-ARS) antibodies are associated with an increased risk of ILD.Objectives:Defining the radiological characteristics of IIM patients, with special focus on serological groups, through qualitative, semiquantitative and quantitative analysis of lung CT.Methods:This was a prospective study conducted from 2016 to 2019. Ninety-eight IIM patients (35 men, 63 women) were included. Myositis specific autoantibodies (MSA) were assessed with Myositis Prophyle III (Euroimmune, Lubeck).Each patient had a baseline CT; the total score of Warrick (WS) was obtained at semiquantitative analysis. The radiological scores ILD% (interstitial lung disease %) and PVRS% (pulmonary vascular related structure) were the result of quantitative analysis in 61 patients (CALIPER). Pulmonary function tests (PFTs) included TLC%, FVC% and DLCO% (65 patients). The analysis was conducted in the whole group and divided in subgroups based on their MSA pattern: in particular anti-ARS (Group 1) and patients negative to MSA (Group 2) were analysed.Results:Positive correlations between ILD% and PVRS% (Rho=0.916; ρ=0.000), WS and ILD% (Rho=0.663; ρ=0.000) and WS and PVRS% (Rho=0.637; ρ<0.001) were found.The most relevant inverse correlations were found between ILD% and DLCO% (Rho=-0.590; ρ=0.001), PVRS% and DLCO% (Rho=-0.549; ρ<0.001) and WS and DLCO% (Rho=-0.471; ρ<0.001).Statistically significant higher values of WS, ILD% and PVRS% were found in Group 1 (WS=15, ILD%=11 and PVRS%=3.5), compared to Group 2 (WS=2.5, ILD%=0.84 and PVRS%=2.2). NSIP pattern resulted dominant represented in the two groups (80% Group 1, 75% Group 2). No statistically significant differences of DLCO%, FVC% and TLCO% were found.Conclusion:The inverse correlations between the radiological scores and the functional data TLC% and DLCO% (ρ<0.001) confirm the role of lung CT in the clinical management of ILD in IIM patients, and may represent a promising tool for clinical trials. For the first time anti-ARS and serological negative patients were defined through qualitative, semiquantitative and quantitative analysis of lung CT. Further study should be conducted in order to define the prognostic value of the quantitative analysis of lung CT in the follow up of IIM patients.Disclosure of Interests:None declared

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