Stéphane Zuily1,2, Isabelle Clerc-Urmès3, Cédric Bauman3, Danieli Andrade4, Savino Sciascia5, Vittorio Pengo6, Maria G Tektonidou7, Amaia Ugarte8, Maria Gerosa9, H Michael Belmont10, Maria Angeles Aguirre Zamorano11, Paul Fortin12, Lanlan Ji13, Maria Efthymiou14, Hannah Cohen14, D Ware Branch15, Guilherme Ramires de Jesus16, Cecilia Nalli17, Michelle Petri18, Esther Rodriguez19, Ricard Cervera20, Jason S Knight21, Tatsuya Atsumi22, Rohan Willis23, Maria Laura Bertolaccini24, Joann Vega25, Denis Wahl1,2, Doruk Erkan25. 1. Vascular Medicine Division and Regional Competence Centre for Systemic And Autoimmune Diseases, Nancy Academic Hospital, Nancy, France. 2. Inserm UMR_S 1116, Lorraine University, Nancy, France. 3. ESPRI-BioBase, Platform of Clinical Research Support PARC (MDS unity), Nancy Academic Hospital, Nancy, France. 4. Department of Rheumatology, Faculty of Medicine, University of Sao Paulo (USP), Sao Paulo, Brazil. 5. Centre of Research of Immunopathology and Rare Diseases, University of Turin, Turin, Italy. 6. Thrombosis Research Laboratory, Department of Cardiac Thoracic and Vascular Sciences, and Public Health, University of Padova; Arianna Foundation on Anticoagulation, Bologna, Italy. 7. First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece. 8. Autoimmune Diseases Research Unit, Department of Internal Medicine, Hospital Universitario Cruces, Barakaldo, Spain. 9. Clinical Rheumatology Unit, Research Center for Adult and Pediatric Diseases, Department of Clinical Sciences and Community Health, ASST Pini-CTO, University of Milan, Milan, Italy. 10. School of Medicine, New York University, New York, USA. 11. Maimonides Institute for Biomedical Research of Cordoba, Cordoba, Spain. 12. CHU de Quebec - Université Laval, Quebec, Canada. 13. Rheumatology and Immunology Department, Peking University First Hospital, Beijing, PR China. 14. Haemostasis Research Unit, Department of Haematology, University College London, London, UK. 15. University of Utah and Intermountain Healthcare, Salt Lake City, USA. 16. Departamento de Obstetrícia, Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. 17. Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia, Brescia, Italy. 18. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. 19. Hospital Universitario 12 de Octubre, Madrid, Spain. 20. Department of Autoimmune Diseases, Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. 21. Division of Rheumatology, University of Michigan, Ann Arbor, USA. 22. Hokkaido University Hospital, Sapporo, Japan. 23. Antiphospholipid Standardization Laboratory, University of Texas Medical Branch, Galveston, USA. 24. Academic Department of Vascular Surgery, King's College London, St Thomas' Hospital, London, UK. 25. Barbara Volcker Centre for Women and Rheumatic Disease, Hospital for Special Surgery, Weill Cornell Medicine, New York, USA.
Abstract
OBJECTIVE: This study aimed to use cluster analysis (CA) to identify different clinical phenotypes among antiphospholipid antibodies (aPL)-positive patients. METHODS: The Alliance for Clinical Trials and International Networking (APS ACTION) Registry includes persistently positive aPL of any isotype based on the Sydney antiphospholipid syndrome (APS) classification criteria. We performed CA on the baseline characteristics collected retrospectively at the time of the registry entry of the first 500 patients included in the registry. A total of 30 clinical data points were included in the primary CA to cover the broad spectrum of aPL-positive patients. RESULTS: A total of 497 patients from international centres were analysed, resulting in three main exclusive clusters: (a) female patients with no other autoimmune diseases but with venous thromboembolism (VTE) and triple-aPL positivity; (b) female patients with systemic lupus erythematosus, VTE, aPL nephropathy, thrombocytopaenia, haemolytic anaemia and a positive lupus anticoagulant test; and (c) older men with arterial thrombosis, heart valve disease, livedo, skin ulcers, neurological manifestations and cardiovascular disease (CVD) risk factors. CONCLUSIONS: Based on our hierarchical cluster analysis, we identified different clinical phenotypes of aPL-positive patients discriminated by aPL profile, lupus or CVD risk factors. Our results, while supporting the heterogeneity of aPL-positive patients, also provide a foundation to understand disease mechanisms, create new approaches for APS classification and ultimately develop new management approaches.
OBJECTIVE: This study aimed to use cluster analysis (CA) to identify different clinical phenotypes among antiphospholipid antibodies (aPL)-positive patients. METHODS: The Alliance for Clinical Trials and International Networking (APS ACTION) Registry includes persistently positive aPL of any isotype based on the Sydney antiphospholipid syndrome (APS) classification criteria. We performed CA on the baseline characteristics collected retrospectively at the time of the registry entry of the first 500 patients included in the registry. A total of 30 clinical data points were included in the primary CA to cover the broad spectrum of aPL-positive patients. RESULTS: A total of 497 patients from international centres were analysed, resulting in three main exclusive clusters: (a) female patients with no other autoimmune diseases but with venous thromboembolism (VTE) and triple-aPL positivity; (b) female patients with systemic lupus erythematosus, VTE, aPL nephropathy, thrombocytopaenia, haemolytic anaemia and a positive lupus anticoagulant test; and (c) older men with arterial thrombosis, heart valve disease, livedo, skin ulcers, neurological manifestations and cardiovascular disease (CVD) risk factors. CONCLUSIONS: Based on our hierarchical cluster analysis, we identified different clinical phenotypes of aPL-positive patients discriminated by aPL profile, lupus or CVD risk factors. Our results, while supporting the heterogeneity of aPL-positive patients, also provide a foundation to understand disease mechanisms, create new approaches for APS classification and ultimately develop new management approaches.
Authors: S Miyakis; M D Lockshin; T Atsumi; D W Branch; R L Brey; R Cervera; R H W M Derksen; P G DE Groot; T Koike; P L Meroni; G Reber; Y Shoenfeld; A Tincani; P G Vlachoyiannopoulos; S A Krilis Journal: J Thromb Haemost Date: 2006-02 Impact factor: 5.824
Authors: Massimo Radin; Savino Sciascia; Doruk Erkan; Vittorio Pengo; Maria G Tektonidou; Amaia Ugarte; Pierluigi Meroni; Lanlan Ji; H Michael Belmont; Hannah Cohen; Guilherme Ramires de Jesús; D Ware Branch; Paul R Fortin; Laura Andreoli; Michelle Petri; Esther Rodriguez; Ignasi Rodriguez-Pinto; Jason S Knight; Tatsuya Atsumi; Rohan Willis; Emilio Gonzalez; Rosario Lopez-Pedrera; Ana Paula Rossi Gandara; Margarete Borges Gualhardo Vendramini; Alessandra Banzato; Ecem Sevim; Medha Barbhaiya; Maria Efthymiou; Ian Mackie; Maria Laura Bertolaccini; Danieli Andrade Journal: Semin Arthritis Rheum Date: 2019-05-02 Impact factor: 5.532
Authors: Angela Tincani; Michael M Ward; Maria G Tektonidou; Laura Andreoli; Marteen Limper; Zahir Amoura; Ricard Cervera; Nathalie Costedoat-Chalumeau; Maria Jose Cuadrado; Thomas Dörner; Raquel Ferrer-Oliveras; Karen Hambly; Munther A Khamashta; Judith King; Francesca Marchiori; Pier Luigi Meroni; Marta Mosca; Vittorio Pengo; Luigi Raio; Guillermo Ruiz-Irastorza; Yehuda Shoenfeld; Ljudmila Stojanovich; Elisabet Svenungsson; Denis Wahl Journal: Ann Rheum Dis Date: 2019-05-15 Impact factor: 19.103
Authors: V Pengo; A Ruffatti; C Legnani; P Gresele; D Barcellona; N Erba; S Testa; F Marongiu; E Bison; G Denas; A Banzato; S Padayattil Jose; S Iliceto Journal: J Thromb Haemost Date: 2009-10-30 Impact factor: 5.824
Authors: Luis Alberto Henríquez-Hernández; Almudena Valenciano; Palmira Foro-Arnalot; María Jesús Alvarez-Cubero; José Manuel Cozar; José Francisco Suárez-Novo; Manel Castells-Esteve; Adriana Ayala-Gil; Pablo Fernández-Gonzalo; Montse Ferrer; Ferrán Guedea; Gemma Sancho-Pardo; Jordi Craven-Bartle; María José Ortiz-Gordillo; Patricia Cabrera-Roldán; Estefanía Herrera-Ramos; Pedro C Lara Journal: PLoS One Date: 2013-07-23 Impact factor: 3.240
Authors: Vera M Ripoll; Francesca Pregnolato; Simona Mazza; Caterina Bodio; Claudia Grossi; Thomas McDonnell; Charis Pericleous; Pier Luigi Meroni; David A Isenberg; Anisur Rahman; Ian P Giles Journal: J Autoimmun Date: 2018-07-19 Impact factor: 7.094