Criteria and non-criteria anti-phospholipid antibodies in the different clinical forms of antiphospholipid syndrome

Oscar Cabrera-Marante¹Daniel Pleguezuelo¹Sara Garcinuño¹Laura Naranjo¹Raquel Diaz-Simon²Francisco Javier Gil Etayo³Denis Zafra⁴Fernando Lozano Morillo⁵Luis Morillas⁵Magdalena Abad⁶Olga Villar⁶Antonio Martínez-Salio⁷Tito Leoncio Lizarraga- Hurtado⁸Estela Paz Artal¹Antonio Serrano^1*Manuel Serrano¹

• ¹Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain
• ²Hospital 12 de Octubre Servicio de Medicina Interna, Madrid, Spain
• ³Hospital Universitario de Salamanca, Salamanca, Spain
• ⁴Hospital Universitario 12 de Octubre servicio de Hematologia y Hemoterapia, Madrid, Spain
• ⁵Hospital Universitario 12 de Octubre servicio de Reumatologia, Madrid, Spain
• ⁶Hospital Universitario 12 de Octubre Servicio de Obstetricia y Ginecologia, Madrid, Spain
• ⁷Hospital Universitario 12 de Octubre Servicio de Neurologia, Madrid, Spain
• ⁸Hospital Universitario 12 de Octubre Servicio de Medicina Ocupacional, Madrid, Spain

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombotic symptoms (venous, arterial or small vessels) and/or gestational morbidity in patients carrying antiphospholipid antibodies (aPL). Criteria aPL are anti cardiolipin, anti Beta 2 glycoprotein I (aB2GPI) of IgG or IgM isotypes and lupus anticoagulant (LA). However, there are aPL associated with APS events but not included in the criteria (extra-criteria). The aim of this study is to evaluate the prevalence and association of criteria and extra-criteria aPL with APS clinical events. Methods: 838 patients with clinical manifestations of APS were studied. 715 presented vascular manifestations and 130 obstetric morbidity. We measured levels of criteria aPL and the extra-criteria aPL determined were anti-phosphatidylserine/prothrombin (aPS/PT) of IgG and IgM isotypes and aB2GPI IgA.Classic-aPL, aPS/PT and aB2GPI IgA positivity showed a significant and independent association with thrombosis (OR: 2.40, 2.36, and 2.53 respectively). IgA aB2GP1 was the only aPL significantly associated to the 5 types of thrombotic events (venous thrombosis, pulmonary embolism, stroke, acute myocardial infarction and arterial thrombosis). Regarding obstetric APS, the most relevant antibodies were classic-aPL of IgM isotype (OR:36.04) and aPS/PT of both isotypes (OR:4.4). The other aPL studied did not show association in multivariate analysis.The degree of clinical association for each group of aPL was different depending on the form of presentation (vascular or obstetric) and the presence or absence of autoimmune diseases. Moreover, a fair level of agreement between LA and aPS/PT positivity was found, therefore, aPS/PT should not be referred as a surrogate marker of LA.