Navid Zohoury1,2,3, Maria Laura Bertolaccini4,5,6, Jose Luis Rodriguez-Garcia4,5,6, Zakera Shums4,5,6, Oier Ateka-Barrutia4,5,6, Maurizio Sorice4,5,6, Gary L Norman4,5,6, Munther Khamashta4,5,6. 1. From Inova Diagnostics Inc., San Diego, California, USA; Academic Department of Vascular Surgery, King's College London; Graham Hughes Lupus Research Laboratory, Lupus Research Unit, The Rayne Institute, Division of Women's Health, King's College London, St. Thomas' Hospital, London, UK; Department of Internal Medicine, University of Castilla-La Mancha, Albacete, Spain; Department of Experimental Medicine, La Sapienza University, Rome, Italy. nzohoury@inovadx.com. 2. Navid Zohoury, Zakera Shums, and Gary L. Norman are employees of Inova Diagnostics. nzohoury@inovadx.com. 3. N. Zohoury, BS, Inova Diagnostics Inc.; M.L. Bertolaccini, PhD, Academic Department of Vascular Surgery, King's College London; J.L. Rodriguez-Garcia, PhD, Department of Internal Medicine, University of Castilla-La Mancha; Z. Shums, MSc, Inova Diagnostics Inc.; O. Ateka-Barrutia, MD, Graham Hughes Lupus Research Laboratory, Lupus Research Unit, The Rayne Institute, Division of Women's Health, King's College London, St. Thomas' Hospital; M. Sorice, MD, Department of Experimental Medicine, La Sapienza University; G.L. Norman, PhD (AGAF, FAASLD), Inova Diagnostics Inc.; M. Khamashta, MD, PhD (FRCP), Graham Hughes Lupus Research Laboratory, Lupus Research Unit, The Rayne Institute, Division of Women's Health, King's College London, St. Thomas' Hospital. nzohoury@inovadx.com. 4. From Inova Diagnostics Inc., San Diego, California, USA; Academic Department of Vascular Surgery, King's College London; Graham Hughes Lupus Research Laboratory, Lupus Research Unit, The Rayne Institute, Division of Women's Health, King's College London, St. Thomas' Hospital, London, UK; Department of Internal Medicine, University of Castilla-La Mancha, Albacete, Spain; Department of Experimental Medicine, La Sapienza University, Rome, Italy. 5. Navid Zohoury, Zakera Shums, and Gary L. Norman are employees of Inova Diagnostics. 6. N. Zohoury, BS, Inova Diagnostics Inc.; M.L. Bertolaccini, PhD, Academic Department of Vascular Surgery, King's College London; J.L. Rodriguez-Garcia, PhD, Department of Internal Medicine, University of Castilla-La Mancha; Z. Shums, MSc, Inova Diagnostics Inc.; O. Ateka-Barrutia, MD, Graham Hughes Lupus Research Laboratory, Lupus Research Unit, The Rayne Institute, Division of Women's Health, King's College London, St. Thomas' Hospital; M. Sorice, MD, Department of Experimental Medicine, La Sapienza University; G.L. Norman, PhD (AGAF, FAASLD), Inova Diagnostics Inc.; M. Khamashta, MD, PhD (FRCP), Graham Hughes Lupus Research Laboratory, Lupus Research Unit, The Rayne Institute, Division of Women's Health, King's College London, St. Thomas' Hospital.
Abstract
OBJECTIVE: Most clinicians use the 2006 Sydney classification criteria to evaluate patients suspected of having antiphospholipid syndrome (APS). Although sensitive and specific for APS, many patients fulfilling clinical criteria for the syndrome are persistently negative for the specific serological tests ("laboratory criteria"). These "seronegative APS" (SN-APS) patients can go undiagnosed and untreated until they experience serious clinical events. This study's objective was to describe antibody profiles of SN-APS patients using non-criteria markers, assess the clinical utility of these markers separately and in combination, and suggest incorporation into guidelines for patients suspected of APS. METHODS: We categorized 175 consecutive patients suspected of APS into 2 subgroups: 107 fulfilling Sydney APS classification for seropositive APS (SP-APS) and 68 with clinical manifestations suggestive of APS but having negative serology, on 2 occasions, for criteria markers (SN-APS). On study inclusion, samples were retested for criteria and 11 non-criteria markers, including antiphosphatidylserine/prothrombin antibodies. RESULTS: Using 4 of 11 non-criteria tests, a cumulative 30.9% of SN-APS patients were detected. Combining results of all 11 non-criteria tests, 25 SN-APS (36.8%) and 89 SP-APS (83.2%) were positive for 1 or more non-criteria antibodies. CONCLUSION: Failure to diagnose APS can result in severe clinical consequences. Patients displaying clinical features of APS, but negative for conventional criteria markers, should undergo additional testing for non-criteria biomarkers. In our cohort, around one-third of SN-APS patients showed reactivity to 1 or more non-criteria markers. An update to the current classification criteria incorporating new serological markers should be considered to identify and stratify patients with APS for more effective treatment and management.
OBJECTIVE: Most clinicians use the 2006 Sydney classification criteria to evaluate patients suspected of having antiphospholipid syndrome (APS). Although sensitive and specific for APS, many patients fulfilling clinical criteria for the syndrome are persistently negative for the specific serological tests ("laboratory criteria"). These "seronegative APS" (SN-APS) patients can go undiagnosed and untreated until they experience serious clinical events. This study's objective was to describe antibody profiles of SN-APSpatients using non-criteria markers, assess the clinical utility of these markers separately and in combination, and suggest incorporation into guidelines for patients suspected of APS. METHODS: We categorized 175 consecutive patients suspected of APS into 2 subgroups: 107 fulfilling Sydney APS classification for seropositive APS (SP-APS) and 68 with clinical manifestations suggestive of APS but having negative serology, on 2 occasions, for criteria markers (SN-APS). On study inclusion, samples were retested for criteria and 11 non-criteria markers, including antiphosphatidylserine/prothrombin antibodies. RESULTS: Using 4 of 11 non-criteria tests, a cumulative 30.9% of SN-APSpatients were detected. Combining results of all 11 non-criteria tests, 25 SN-APS (36.8%) and 89 SP-APS (83.2%) were positive for 1 or more non-criteria antibodies. CONCLUSION: Failure to diagnose APS can result in severe clinical consequences. Patients displaying clinical features of APS, but negative for conventional criteria markers, should undergo additional testing for non-criteria biomarkers. In our cohort, around one-third of SN-APSpatients showed reactivity to 1 or more non-criteria markers. An update to the current classification criteria incorporating new serological markers should be considered to identify and stratify patients with APS for more effective treatment and management.
Authors: Marteen Limper; Carlo Alberto Scirè; Rosaria Talarico; Zahir Amoura; Tadej Avcin; Martina Basile; Gerd Burmester; Linda Carli; Ricard Cervera; Nathalie Costedoat-Chalumeau; Andrea Doria; Thomas Dörner; João Eurico Fonseca; Ilaria Galetti; Eric Hachulla; David Launay; Filipa Lourenco; Carla Macieira; Pierluigi Meroni; Carlo Maurizio Montecucco; Maria Francisca Moraes-Fontes; Luc Mouthon; Cecilia Nalli; Veronique Ramoni; Maria Tektonidou; Jacob M van Laar; Stefano Bombardieri; Matthias Schneider; Vanessa Smith; Ana Vieira; Maurizio Cutolo; Marta Mosca; Angela Tincani Journal: RMD Open Date: 2018-10-18
Authors: Manuel Serrano; Laura Morán; Jose Angel Martinez-Flores; Esther Mancebo; Daniel Pleguezuelo; Oscar Cabrera-Marante; Juan Delgado; Antonio Serrano Journal: Front Immunol Date: 2019-12-23 Impact factor: 7.561
Authors: Oscar Cabrera-Marante; Edgard Rodríguez de Frías; Manuel Serrano; Fernando Lozano Morillo; Laura Naranjo; Francisco J Gil-Etayo; Estela Paz-Artal; Daniel E Pleguezuelo; Antonio Serrano Journal: Int J Mol Sci Date: 2020-11-26 Impact factor: 5.923