Importance of antiphospholipid antibodies of the IgA class for the prognosis of antiphospholipid syndrome

• Grant number: 20/06156-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2020
• End date: June 30, 2021
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Fernanda Loureiro de Andrade Orsi
• Grantee: Luísa Reis Figueiredo Pinto
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 16/14172-6 - Investigation of the pathophysiological aspects and novel therapeutic approaches for thromboembolic disorders, AP.TEM

Abstract

Antiphospholipid syndrome (APS) is an autoimmune disease, with recurrent thromboembolic disorders, or pregnancy complications, associated with the presence of antiphospholipid antibodies, anticardiolipin autoantibodies (aCL) IgG or IgM, anti-beta 2 glycoprotein 1 (a²2GPI) IgG or IgM and lupus anticoagulant (LAC). APS can be primary or secondary to another autoimmune disease. In addition to diagnostic markers, aPL are responsible for the initial pathophysiological changes that result in the clinical complications observed in APS. Although the aCL and a²2GP1 IgA isotypes were not included as a diagnostic criterion for APS, the presence of these antibodies is prevalent in the disease. However, the results regarding the association of IgA and complications of APS are conflicting and their role and importance in APS are unclear. Therefore, the objective of this work is to evaluate the role of aCL and a²2GP1 antibodies of the IgA class in the clinical presentation and evolution of patients with primary APS, as well as possible determining factors for the positivity of these IgA isotypes. In a cohort of patients with APS, we will assess the prevalence of IgA aCL and a²2GP1 antibodies; we will compare the demographic, laboratory and clinical profile of the subgroups of positive and negative patients for aCL and a²2GP1 of the IgA class; we will compare the concentration of IgA isotypes between the different positivity profiles (single, double or triple positivity) for the diagnostic aPL (LAC, aCL and a²2GP1 IgM and IgG); we will assess possible determinants of positivity for IgA and the association between positive IgA aCL and a²2GP with the clinical evolution of patients. Comparison analyzes will be performed using Fisher's tests (categorical variables), Kruskal Wallis (continuous variables of non-normal distribution) or ANOVA (continuous variables of non-normal distribution). The evaluation of possible determinants of positivity for IgA (aCL or a²2GP1) and the association between positivity for IgA (aCL or a²2GP1) and clinical outcomes will be made using regression models. With the results of this work, we hope to be able to describe the clinical relevance of IgA aCL and IgA a²2GP1 antibodies in the context of APS and, possibly, suggest new markers for the prognosis of the disease.