Clinical aspects
Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank
A. Loganathan1, G. Zanframundo2, A. Yoshida3, S. Faghihi-Kashani4, I. Bauer Ventura5, E. Dourado6, F. Bozan7, G. Sambataro8, Y. Yamano9, S.S. Bae10, D. Lim11, A. Ceribelli12, N. Isailovic13, C. Selmi14, N. Fertig15, E. Bravi16, Y. Kaneko17, A.P. Saraiva18, V. Jovani19, J. Bachiller-Corral20, J. Cifrian21, A. Mera-Varela22, S. Moghadam-Kia23, V. Wolff24, J. Campagne25, A. Meyer26, M. Giannini27, K. Triantafyllias28, J. Knitza29, L. Gupta30, Y. Molad31, F. Iannone32, I. Cavazzana33, M. Piga34, G. De Luca35, S. Tansley36, E. Bozzalla-Cassione37, F. Bonella38, T.J. Corte39, T.J. Doyle40, D. Fiorentino41, M.A. Gonzalez-Gay42, M. Hudson43, M. Kuwana44, I.E. Lundberg45, A.L. Mammen46, N.J. Mchugh47, F.W. Miller48, C. Montecucco49, C.V. Oddis50, J. Rojas-Serrano51, J. Schmidt52, C.A. Scirè53, A. Selva-O'callaghan54, V.P. Werth55, C. Alpini56, S. Bozzini57, L. Cavagna58, R. Aggarwal59
Collaborator/s: V. Agarwal1, M. Fornaro2, M.L. Alberti3, M. Needham4, F. Houssiau5, S. Shinjo6, P. Basharat7, Q. Wang8, G. Quintana9, L. Gallay10, E. Ebstein11, C. Fiehn12, E. Feist13, M. Schneider14, U. Drott15, R.E. Voll16, K. Danko17, V. Shobha18, L. Rajasekhar19, M.G. Danieli20, M. Limonta21, M. Matucci-Cerinic22, G. Emmi23, P. Parronchi24, E. Bargagli25, L. Maggi26, M. Sebastiani27, F. Luppi28, P.P. Sainaghi29, E. Bartoloni30, S. Barsotti31, R. Nakashima32, N. Pipitone33, V. Riccieri34, G. Sebastiani35, S. Scarpato36, L. Cantarini37, A. Berti38, P.L. Colombelli39, P. Tomietto40, C. Lomater41, L. Quartuccio42, G. Orsolini43, Y. Kondo44, N. Kimura45, M. Vazquez-Del mercado46, H. Andersson47, J.E. Cabral De Fonseca48, S. Prieto-González49, M.G. Greco Merino50, S. Castaneda51, J.M. Barrio52, L. Nuno53, I.R. Pintó54, J.C. Alén55, L. Sáez-Comet56, G. Cagnotto57, E. Alpsoy58, H. Chinoy59, E. Schiopu60, P. Gandiga61, M.M. Dimachkie62, C. Charles-Schoeman63, E. Wilfong64, G. Marder65, H. Gunawardena66, D. Ghetie67
- Royal National Hospital for Rheumatic Diseases, Bath; Department of Life Sciences, University of Bath, UK; and Arthritis Australia, Broadway, Glebe, NSW, Australia.
- Department of Internal Medicine and Therapeutics, Università di Pavia; and Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
- Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA.
- Department of Medicine, Section of Rheumatology, University of Chicago, IL, USA.
- Rheumatology Department, Centro Hospitalar do Baixo Vouga, Aveiro; Aveiro Rheumatology Research Centre, Egas Moniz Health Alliance, Aveiro; and Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Portugal.
- Hospital Clínico Universidad de Chile, Department of Medicine, Section of Rheumatology, Chile.
- Regional Referral Center for Rare Lung Disease, Policlinico G. Rodolico-San Marco, University of Catania, Italy.
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, Japan.
- Department of Medicine, Division of Rheumatology, David Geffen School of Medicine, University of California Los Angeles, CA, USA.
- Department of Dermatology, Perelman School of Medicine & Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, PA, USA.
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele; and Rheumatology and Clinical Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Italy.
- Rheumatology and Clinical Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Italy.
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele; and Rheumatology and Clinical Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Italy.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- Ospedale Guglielmo da Saliceto, Piacenza, Italy.
- Keio University School of Medicine, Tokyo, Japan.
- Centro Hospitalar e Universitário de Coimbra, Portugal.
- Department of Rheumatology, Hospital General Universitario Dr. Balmis Alicante, ISABIAL, Alicante, Spain.
- Hospital Universitario Ramon y Cajal, Madrid, Spain.
- Hospital Universitario Marques de Valdecilla, IDIVAL, University of Cantabria, Santander, Spain.
- Hospital Clínico Universitario de Santiago de Compostela, Spain.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- Instituto Nacional del Torax, Santiago, Chile.
- HP Metz, Hopital Belle-Ile, Metz, France.
- Exploration Fonctionnelle Musculaire, Service de Physiologie, Service de Rhumatologie, Centre de Référence des Maladies Auto-Immunes Systémiques Rares RESO Hôpitaux Universitaires de Strasbourg, France.
- Exploration Fonctionnelle Musculaire, Service de Physiologie, Service de Rhumatologie, Centre de Référence des Maladies Auto-Immunes Systémiques Rares RESO Hôpitaux Universitaires de Strasbourg, France.
- ACURA Center for Rheumatic Diseases, Bad Kreuznach, Germany.
- University of Erlangen, Germany.
- Department of Clinical Immunology and Rheumatology, SGPGIMS, Lucknow, India.
- Rabin Medical Center, Beilinson Hospital, and Sackler Faculty of Medicine, Tel Aviv University, Israel.
- University of Bari, Italy.
- University and AO Spedali Civili, Brescia, Italy.
- University Clinic and AOU of Cagliari, Italy.
- IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy.
- Royal National Hospital for Rheumatic Diseases, Bath, and Department of Life Sciences, University of Bath, UK.
- Department of Internal Medicine and Therapeutics, Università di Pavia, and Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
- Center for Interstitial and Rare Lung Diseases, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany.
- University of Sydney, NSW, and Royal Prince Alfred Hospital, NSW, Australia.
- Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
- Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA.
- Medicine and Psychiatry Department, University of Cantabria, and Division of Rheumatology, IIS-Fundacion Jiménez Díaz, Madrid, Spain.
- Department of Medicine, McGill University, Montreal, Quebec, Canada.
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
- Karolinska Institute, Stockholm, Sweden.
- National Institute of Arthritis and Musculoskeletal and Skin Disorders, National Institutes of Health, Bethesda, MD, and Departments of Medicine and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Department of Life Sciences, University of Bath, UK.
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, USA.
- Department of Internal Medicine and Therapeutics, Università di Pavia; and Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- Interstitial Lung Disease and Rheumatology Units, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, México City, México.
- University of Gottingen, Germany.
- IRCCS San Gerardo dei Tintori Foundation, Monza, and School of Medicine, University of Milano Bicocca, Milan, Italy.
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Vall d’Hebron General Hospital, Universitat Autonoma de Barcelona, Spain.
- Department of Dermatology, Perelman School of Medicine & Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, PA, USA.
- Laboratory of Biochemical-Chemistry, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
- US Transplant Center, Laboratorio di Biologia Cellulare e Immunologia, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
- Department of Internal Medicine and Therapeutics, Università di Pavia; and Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. lorenzo.cavagna@unipv.it
- Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- Department of Clinical Immunology and Rheumatology, SGPGIMS, Raebareli Road, Lucknow 226014, India
- University of Bari, Italy
- Hospital María Ferrer
- Fiona Stanley Hospital, Murdoch University, Notre Dame University, Perron Institute
- Clinique Universitaire Saint Luc
- Faculdade de Medicina, Universidade de Sao Paulo
- University of Western Ontario
- Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences
- Universidad Nacional de Colombia/Fundacion Santa fe de Bogota
- CHU Lyon
- Bichat-Claude Bernard Hospital
- Medical Center Baden-Baden
- Helios Gesundheit
- University Medical Center Dusseldorf
- Johann Wolfgang Goethe-Universität, Frankfurt
- University Medical Center of Freiburg
- University of Debrecen
- St John's National Academy of Medical Sciences, Bangalore
- Nizam's Institute of Medical Sciences
- Clinical Medicine, University of Ancona
- ASST Papa Giovanni XXIII, Bergamo
- University of Florence
- University of Florence
- University of Florence, Dept. Experimental and Clinical Medicine, Florence
- U.O.C. Malattie Respiratorie Dip. Scienze Mediche, Chirurgiche e Neuroscienze, Università di Siena Policlinico ""Le Scotte"
- Fondazione IRCCS Istituto Neurologico Carlo Besta
- Azienda Ospedaliera Universitaria di Modena
- Univerity of Milano Bicocca, San Gerardo Hospital, Monza
- Università del Piemonte Orientale UPO, Novara
- University of Perugia
- Azienda Ospedaliera Universitaria Pisana, Pisa
- Graduate School of Medicine, Kyoto University, Kioto
- IRCCS ASMN Reggio Emilia
- University La Sapienza and Policlinico Umberto I, Rome
- Ospedale San Camillo, Roma
- Ospedale " Scarlato" Scafati
- Azienda Ospedaliera Universitaria Senese - Ospedale Santa Maria alle Scotte
- Ospedale Sant'Anna, Trento
- ASST Bergamo Ovest - Treviglio Hospital
- University Hospital of Cattinara, Trieste
- Ospedale Mauriziano, Turin
- Santa Maria della Misericordia Hospital and University of Udine
- Verona University
- Tosei General Hospital, Seto
- Tokyo Medical and Dental University, TMDU, Bunkyo-ku
- OPD Hospital Civil Dr. Juan I. Menchaca
- Oslo University Hospital
- Centro Hospitalar Lisboa Norte
- Hospital Clínic of Barcelona/IDIBAPS - University of Barcelona
- Hospital Universitario Dr. Negrín, Las Palmas
- Hospital Universitario de la Princesa, IIS-Princesa, Madrid
- Hospital General Universitario Gregorio Marañón, Madrid
- Hospital Universitario La Paz, Madrid
- Hospital Universitari Mutua Terrassa, Terrassa
- Hospital Universitario Araba
- Hospital Universitario Miguel Servet, Zaragoza
- Lund University and Skåne University Hospital Malmö
- Akdeniz University, School of Medicine
- University of Manchester, UK
- Michigan Medicine, University of Michigan
- Emory University
- University of Kansas Medical Center
- University of California, Los Angeles
- Vanderbilt University Medical Center
- Northwell Health
- North Bristol NHS Trust, UK
- Oregon Health & Science University
CLASS Project
CER17264
2024 Vol.42, N°2
PI 0277, PF 0287
Clinical aspects
Free to view
(click on article PDF icon to read the article)
PMID: 38488094 [PubMed]
Received: 02/11/2023
Accepted : 18/01/2024
In Press: 14/03/2024
Published: 14/03/2024
Abstract
OBJECTIVES:
The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an “ad-interim” study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity.
METHODS:
We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient.
RESULTS:
Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and “other” methods.
CONCLUSIONS:
Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.