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      Anti-Aminoacyl Transfer-RNA-Synthetases (Anti-tRNA) Autoantibodies Associated with Interstitial Lung Disease: Pulmonary Disease Progression has a Persistent Elevation of the Th17 Cytokine Profile

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          Abstract

          Anti-tRNA autoantibodies are associated with interstitial lung disease (ILD), in at least two clinical scenarios: the anti-synthetase syndrome (ASSD) and interstitial pneumonia with autoimmune features (IPAF). Under pathological conditions, cytokines indicate the participating elements and the course of inflammatory phenomena. We aimed to quantify serum concentrations of different inflammatory cytokines profiles in patients with anti-tRNA associated ILD (anti-tRNA-ILD) and estimate the association between these and ILD improvement and progression. Serum levels of 18 cytokines from baseline and after six months of treatment of ILD patients’ positives to anti-tRNA were included in the current study. At six months, patients were classified as with or without ILD progression. A total of 39 patients were included (10 anti-Jo1, eight anti-PL7, 11 anti-PL12, and 10 anti-Ej). Three patients (7.6%) had ILD progression (progressors patients, PP) and showed statistically higher levels in IL-4, IL-10, IL-17A, IL-22, GM-CSF, IL-1β, IL-6, IL-12, IL-18, and TNF-α, compared to patients without disease progression (no progressors patients, NPP). IL-17A, IL-1β, and IL-6 (T-helper-lymphocyte (Th)17 inflammatory cytokine profile) were elevated and had a high discriminatory capacity in distinguishing ILD PP of those NPP at follow-up. Overall, there is an association between the cytokines of the Th17 inflammatory profile and the ASSD progression.

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          Most cited references25

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          Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review.

          Autoantibodies are a hallmark in the diagnosis of many systemic autoimmune rheumatic diseases (SARD) including idiopathic inflammatory myopathies (IIM). Based on their specificity, autoantibodies in IIM are grouped into myositis specific (MSA) and myositis associated autoantibodies (MAA). Among the MSA, autoantibodies against aminoacyl-tRNA synthetases (ARS) represent the most common antibodies and can be detected in 25-35% of patients. The presence of ARS and other autoantibodies has become a key feature for classification and diagnosis of IIM and is increasingly used to define clinically distinguishable IIM subsets. For example, anti-ARS autoantibodies are the key features of what has become known as anti-synthetase syndrome (aSS), characterized by multiple organ involvement, primarily interstitial lung disease, often accompanied by myositis, non-erosive arthritis, Raynaud's phenomenon, fever, and "mechanic's hands". Autoantibodies directed to eight different ARS have been described: Jo-1 (histidyl), PL-7 (threonyl), PL-12 (alanyl), OJ (isoleucyl), EJ (glycyl), KS (asparaginyl), Zo (phenylalanyl) and Ha (tyrosyl). Each anti-ARS antibody seems to define a distinctive clinical phenotype. Although several research methods and commercial tests are available, routine testing for anti-ARS autoantibodies (other than anti-Jo-1/histidyl-tRNA synthetase) is not widely available, sometimes leading to delays in diagnosis and poor disease outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.
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            A longitudinal cohort study of the anti-synthetase syndrome: increased severity of interstitial lung disease in black patients and patients with anti-PL7 and anti-PL12 autoantibodies.

            The aim was to study the prevalence, rate of appearance and severity of clinical features in patients with different anti-synthetase syndrome (ASyS) autoantibodies.
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              Interstitial lung disease in anti-Jo-1 patients with antisynthetase syndrome.

              To assess the outcome of interstitial lung disease (ILD) in anti-Jo-1 patients with antisynthetase syndrome, determine predictive variables of ILD deterioration in these patients, and compare features of anti-Jo-1 patients with and without ILD. Ninety-one anti-Jo-1 patients were identified by medical records search in 4 medical centers. All of these patients had undergone pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) scans. Sixty-six patients (72.5%) had ILD. Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n = 12), progressive onset of lung signs (n = 35), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT scans (n = 19). Sixteen patients had resolution of ILD; 39 and 11 patients experienced improvement and deterioration of ILD, respectively. ILD led to decreased functional status, since 29.8% of patients exhibited a marked reduction of activities due to ILD and 13.6% had respiratory insufficiency requiring oxygen therapy; 5 of 6 patients died due to ILD complications. Predictive parameters of ILD deterioration were HRCT scan pattern of usual interstitial pneumonia, respiratory muscle involvement, and age ≥55 years. Furthermore, anti-Jo-1 patients with ILD, compared with those without, more frequently exhibited mechanic's hands and lower creatine kinase levels. Our findings confirm that ILD is a frequent complication in anti-Jo-1 patients, resulting in high morbidity. We suggest that patients with predictive factors of ILD deterioration may require more aggressive therapy. Finally, anti-Jo-1 patients with ILD, compared with those without, may exhibit a particular clinical phenotype. Copyright © 2013 by the American College of Rheumatology.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                06 May 2020
                May 2020
                : 9
                : 5
                : 1356
                Affiliations
                [1 ]Experimental Medicine Research Unit, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 06720, Mexico; espiri77mx@ 123456yahoo.com.mx
                [2 ]HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico; rfalfanv@ 123456iner.gob.mx (R.F.-V.); glofos@ 123456yahoo.com.mx (G.P.-R.)
                [3 ]Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico; medithmejia1965@ 123456gmail.com (M.M.); ixchelglez19@ 123456gmail.com (M.I.G.-P.); dr_heidegger@ 123456msn.com (H.N.M.-T.)
                [4 ]Translational Research Laboratory on Aging and Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico; ivettebu@ 123456yahoo.com.mx
                [5 ]Profesor, Programa de Maestría y Doctorado en Ciencias Médicas, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 14080, Mexico
                Author notes
                [* ]Correspondence: jrojas@ 123456iner.gob.mx
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-6877-8124
                https://orcid.org/0000-0002-6876-1012
                https://orcid.org/0000-0002-2825-506X
                Article
                jcm-09-01356
                10.3390/jcm9051356
                7290669
                32384594
                5cf48f04-2ee1-4dbe-929e-55e0c5191077
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 March 2020
                : 27 April 2020
                Categories
                Article

                anti-synthetase syndrome,interstitial lung disease,inflammatory cytokine profile,il-17a,th17

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