Evaluation of the role of isotype IgM antiphospholipid antibodies in the clinical manifestations of thrombotic antiphospholipid syndrome

• Grant number: 25/06564-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Fernanda Loureiro de Andrade Orsi
• Grantee: Júlia Cerchiari de Godói
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/13216-0 - Crosstalk between hemostasis and innate immunity (Immunothrombosis): pathogenic, diagnostic and therapeutic implications in infectious and inflammatory diseases, AP.TEM

Abstract

Antiphospholipid syndrome (APS) is an autoimmune disease defined by arterial, venous, or microcirculation thrombotic manifestations and obstetric complications, which occur in the presence of positivity for one or more antiphospholipid antibodies (aPL): lupus anticoagulant (LA), anticardiolipin antibody (aCL) and/or anti-¿2-glycoprotein-1 antibody (a¿2GP1). These antibodies create a prothrombotic state, which favors the occurrence of clinical manifestations of the disease at times of vascular injury or inflammation. Thus, the pathophysiology involves endothelial, platelet, neutrophilic, and complement system activation. APS has as diagnostic criteria at least 1 clinical manifestation (thrombotic or obstetric) occurring along with at least 1 positive laboratory criterion (detection of LA, aCL IgG/IgM and/or a¿2GP1 IgG/IgM). However, there are doubts about the role of IgM class antibodies in the pathophysiology of thrombotic APS, as they are generally transient isotypes, associated with infectious conditions and have a better established role in obstetric APS. This uncertainty is reflected in the revision of the diagnostic criteria published in the study "2023 ACR/EULAR APS classification criteria".Therefore, the main objective of this study is to assess whether the thrombotic manifestations of APS are different between patients with isolated presence of IgM class antibodies (aCL and a¿2GP1) and patients with other aPL, based on a retrospective cohort of patients diagnosed with primary thrombotic APS, followed up at the Hematology and Hemotherapy Center of the State University of Campinas (Hemocentro-UNICAMP). The demographic and clinical data of these patients will be collected from electronic medical records. Outcomes related to the type of thrombosis, recurrence of thrombosis and other manifestations of APS will be compared between the group with isolated IgM antibodies and the remaining patients. As a result, we expect to identify the clinical relevance of the isolated presence of IgM aCL and IgM a¿2GP1 for the prognosis of APS. (AU)