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J Clin Med. 2019 Nov 18;8(11). pii: E2013. doi: 10.3390/jcm8112013.

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course.

Cavagna L1, Trallero-Araguás E2, Meloni F3, Cavazzana I4, Rojas-Serrano J5, Feist E6, Zanframundo G1, Morandi V1, Meyer A7,8, Pereira da Silva JA9, Matos Costa CJ9, Molberg O10, Andersson H10, Codullo V11, Mosca M12, Barsotti S12, Neri R12, Scirè C13, Govoni M13, Furini F13, Lopez-Longo FJ14, Martinez-Barrio J14, Schneider U6, Lorenz HM15, Doria A16, Ghirardello A16, Ortego-Centeno N17, Confalonieri M18, Tomietto P19, Pipitone N20, Rodriguez Cambron AB21, Blázquez Cañamero MÁ21, Voll RE22, Wendel S22, Scarpato S23, Maurier F24, Limonta M25, Colombelli P26, Giannini M8, Geny B8, Arrigoni E27, Bravi E27, Migliorini P28, Mathieu A29, Piga M29, Drott U30, Delbrueck C30, Bauhammer J31, Cagnotto G32, Vancheri C33, Sambataro G33, De Langhe E34, Sainaghi PP35, Monti C36, Gigli Berzolari F36, Romano M37, Bonella F38, Specker C39, Schwarting A40, Villa Blanco I41, Selmi C42, Ceribelli A42, Nuno L43, Mera-Varela A44, Perez Gomez N44, Fusaro E45, Parisi S45, Sinigaglia L46, Del Papa N46, Benucci M47, Cimmino MA48, Riccieri V49, Conti F49, Sebastiani GD50, Iuliano A50, Emmi G51, Cammelli D52, Sebastiani M53, Manfredi A53, Bachiller-Corral J54, Sifuentes Giraldo WA54, Paolazzi G55, Saketkoo LA56, Giorgi R57, Salaffi F58, Cifrian J59, Caporali R60, Locatelli F1, Marchioni E61, Pesci A62, Dei G62, Pozzi MR62, Claudia L63, Distler J64, Knitza J64, Schett G64, Iannone F65, Fornaro M65, Franceschini F4, Quartuccio L66, Gerli R67, Bartoloni E67, Bellando Randone S68, Zampogna G69, Gonzalez Perez MI5, Mejia M5, Vicente E70, Triantafyllias K71, Lopez-Mejias R72, Matucci-Cerinic M68, Selva-O'Callaghan A2, Castañeda S70,73, Montecucco C1, Gonzalez-Gay MA72.

Author information

1
Department of Rheumatology, University and IRCCS Policlinico S. Matteo Foundation of Pavia and ERN ReCONNET, 27100 Pavia, Italy.
2
Department of Internal Medicine, Vall d'Hebron General Hospital, Universitat Autonoma de Barcelona, GEAS group, 08035 Barcelona, Spain.
3
Department of Pneumology, University and IRCCS Policlinico S. Matteo Foundation of Pavia and ERN Lung, 27100 Pavia, Italy.
4
Department of Rheumatology, University and ASST Spedali Civili-Brescia and ERN ReCONNET, 25123 Brescia, Italy.
5
Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, 14080 Mexico City, Mexico.
6
Department of Rheumatology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
7
Department of Rheumatology, Hôpitaux Universitaires de Strasbourg and ERN ReCONNET, 67000 Strasbourg, France.
8
Service de Physiologie des Explorations Fonctionnelles, NHC Strasbourg, Université de Strasbourg, 67000 Strasbourg, France.
9
Department of Rheumatology, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal.
10
Department of Rheumatology, Oslo University Hospital, 0372 Oslo, Norway.
11
Department of Rheumatology, Cochin Hospital, 75014 Paris, France.
12
Department of Rheumatology, Azienda Ospedaliera Universitaria Pisana, Pisa and ERN ReCONNET, 56126 Pisa, Italy.
13
Department of Rheumatology, Azienda Ospedaliero Universitaria S. Anna, 44124 Ferrara, Italy.
14
Department of Rheumatology, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.
15
Department of Rheumatology, University of Heidelberg, 69117 Heidelberg, Germany.
16
Department of Rheumatology, University of Padua and ERN ReCONNET, 35122 Padova, Italy.
17
Department of Rheumatology, Hospital Universitario San Cecilio, 18016 Granada, Spain.
18
Department of Pneumology, University Hospital of Cattinara, 34149 Trieste, Italy.
19
Department of Rheumatology, University Hospital of Cattinara, 34149 Trieste, Italy.
20
Department of Rheumatology, S. Maria Hospital-IRCCS, 42123 Reggio Emilia, Italy.
21
Department of Rheumatology, Severo Ochoa Hospital, 28911 Madrid, Spain.
22
Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.
23
Department of Rheumatology, Ospedale " Scarlato" Scafati, 84018 Scafati, Italy.
24
Department of Rheumatology, HP Metz, Hopital Belle-Ile, 57000 Metz, France.
25
Department of Rheumatology, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy.
26
Department of Rheumatology, Ospedale di Treviglio, 24047 Treviglio, Italy.
27
Department of Rheumatology, Ospedale Guglielmo da Saliceto, 29121 Piacenza, Italy.
28
Department of Immunology, Azienda Ospedaliera Universitaria Pisana, Pisa and ERN ReCONNET, 56126 Pisa, Italy.
29
Department of Rheumatology, University Clinic and AOU of Cagliari, 09100 Cagliari, Italy.
30
Department of Rheumatology, Johann Wolfgang Goethe-Universität, 60590 Frankfurt, Germany.
31
Department of Rheumatology, ACURA Centre for Rheumatic Diseases, 76530 Baden-Baden, Germany.
32
Department of Rheumatology, Skane University Hospital, 22242 Lund, Sweden.
33
Department of Pneumology, AOU Catania, 95100 Catania, Italy.
34
Department of Rheumatology, University Hospitals, 3000 Leuven, Belgium.
35
Department of Rheumatology at CAAD, DiMet, University of Eastern Piedmont (UPO) and AOU "Maggiore della Carità", 28100 Novara, Italy.
36
Department of Public Health, Unit of Biostatistics and Clinical Epidemiology, University of Pavia, 27100 Pavia, Italy.
37
Department of Rheumatology, Niguarda Hospital, 20162 Milan, Italy.
38
Department of Pneumology, Ruhrlandklinik, University of Duisburg-Essen and ERN Lung, 45239 Essen, Germany.
39
Department of Rheumatology, Ruhrlandklinik, University of Duisburg-Essen, 45239 Essen, Germany.
40
Department of Rheumatology, Johannes Gutenberg-University, 55122 Mainz, Germany.
41
Department of Rheumatology, Sierrallana Hospital, 39300 Torrelavega, Spain.
42
Department of Rheumatology, Humanitas Research Hospital, Rozzano, 20089 Milan, Italy.
43
Department of Rheumatology, Hospital Universitario La Paz, 28046 Madrid, Spain.
44
Department of Rheumatology, Hospital Clínico Universitario de Santiago de Compostela, 15702 Santiago de Compostela, Spain.
45
Department of Rheumatology, Città della Salute e della Scienza, 10126 Turin, Italy.
46
Department of Rheumatology, Hospital G. Pini-CTO, 20122 Milan, Italy.
47
Department of Rheumatology, Azienda Ospedaliera San Giovanni di Dio, 50143 Firenze, Italy.
48
Department of Rheumatology, University of Genova 16126 Genova, Italy.
49
Department of Rheumatology, University La Sapienza and Policlinico Umberto I, 00161 Rome, Italy.
50
Department of Rheumatology, Ospedale San Camillo, 00152 Rome, Italy.
51
Department of Internal Medicine, AOU Careggi, 50134 Firenze, Italy.
52
Department of Immunology, AOU Careggi, 50134 Firenze, Italy.
53
Department of Rheumatology, Azienda Ospedaliera Universitaria di Modena, 41125 Modena, Italy.
54
Department of Rheumatology, Hospital Universitario Ramon y Cajal, 28034 Madrid, Spain.
55
Department of Rheumatology, Ospedale Santa Chiara, 38122 Trento, Italy.
56
University Medical Center- Comprehensive Pulmonary Hypertension Center & Interstitial Lung Disease Clinic Programs, Louisiana State University and Tulane University Schools of Medicine, Pulmonary Division New Orleans, New Orleans, LA 1542, USA.
57
Department of Rheumatology, ASL Cuneo 2, 12051 Alba, Italy.
58
Department of Rheumatology, Polytechnic University of Marche, C. Urbani Hospital, 60035 Jesi, Italy.
59
Department of Pneumology, Hospital Universitario Marques de Valdecilla, IDIVAL, University of Cantabria Santander, 39008 Santander, Spain.
60
Department of Clinical Sciences and Community Health, University of Milan and Gaetano Pini Hospital, 20122 Milan, Italy.
61
Department of Neurology, IRCCS Mondino Foundation, 27100 Pavia, Italy.
62
Department of Pneumology, Univerity of Milano Bicocca, San Gerardo Hospital, 20900 Monza, Italy.
63
Department of Rheumatology, Mauriziano Hospital, 10126 Turin, Italy.
64
Department of Internal Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
65
Rheumatology Unit-DETO, University of Bari, 70121 Bari, Italy.
66
Clinic of Rheumatology, Department of Medicine, Santa Maria della Misericordia Hospital and University of Udine, 33100 Udine, Italy.
67
Rheumatology Unit, Department of Medicine, University of Perugia, 06129 Perugia, Italy.
68
Department of Rheumatology, AOU Careggi, 50134 Firenze, Italy.
69
Department of Rheumatology, AO Brunico, 39031 Bruneck, Italy.
70
Department of Rheumatology, Hospital Universitario de la Princesa, IIS-Princesa, 28006 Madrid, Spain.
71
Department of Rheumatology, ACURA Center for Rheumatic Diseases, 55543 Bad Kreuznach, Germany.
72
Department of Rheumatology, Hospital Universitario Marques de Valdecilla, IDIVAL, University of Cantabria Santander, 39008 Santander, Spain.
73
Catedra UAM-Roche, EPID Future, Universitad Autonoma de Madrid, 28006 Madrid, Spain.

Abstract

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.

KEYWORDS:

antisynthetase antibodies; antisynthetase syndrome; arthritis; interstitial lung disease; myositis

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