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Role of anti-phospholipase A2 receptor antibody in membranous nephropathy patients in Latin population

Grant number: 16/01761-3
Support type:Regular Research Grants
Duration: March 01, 2017 - February 28, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Luis Yu
Grantee:Luis Yu
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Denise Maria Avancini Costa Malheiros ; Leila Antonangelo

Abstract

Membranous nephropathy (MN) is a commom cause of nephrotic syndrome, with an estimated incidence of 5-10 cases/million inhabitants/year in north Europe. In Brasil, MN is the second most frequent glomerulopathy according to Registro Paulista de Glomerulopatias and also, it was the second most prevalent glomerulopathy in another brazilian series of biopsies. Pathogenesis of MN since the initial description by Jones in 1957, has been an epic journey. For many years, experimental studies have been utilizing the Heymann nephritis model, where renal tubules antigens are actively or passively injected to rodents, causing the development of a glomerulonephritis similar to membranous nephropathy. Many years later, in 2009, Beck et al have performed a seminal discovery, i.e, the presence of antibodies against the PLA2 receptor in 70-80% of idiopathic MN patients. In this study, it was demonstrated the presence of a 185 kD glycoprotein, identified as phospholipase A2 type M receptor. It was also detected auto antibodies against this protein. In addition, eluted IgG from glomerular deposits from MN patients have recognized that glycoprotein, which is ordinarily present in the podocytes and in the immunecomplexes present in the MN glomeruli. Therefore, they have demonstrated the important role of PLA2R in the pathogenesis of idiopathic MN through the relationship between PLA2R gene polymorphisms and disease development. Some studies have demonstrated the presence of PLA2R auto antibodies (PLA2R Ac) in 60-80% of idiopathic MN patients. Other studies have correlated the PLA2R Ac serum levels with proteinuria, time for remission or disease flare. However, no definite conclusions have been drawn because most of these studies were based on transversal cohorts with small samples and specific populations, such as caucasian or chinese. Hosfstra et al in 2012, have demonstrated that PLA2R Ac elisa test presented good correlation with the classic indirect immunefluorescence test (IIFF). Additionally, they have demonstrated that PLA2R Ac serum levels correlated with basal proteinuria and disease remission in a caucasian population. Furthermore, PLA2R Ac may be detected in renal tissue samples by immunefluorescence or immunehistochemistry. Debiec and Ronco in 2011, have demonstrated greater positivity in the renal tissue compared to serum levels in MN patients.Identification of the PLA2R antibodies in the serum and renal tissue of MN patients have never been performed in a brazilian population. Therefore, this study aims to detect these antibodies in MN patients with confirmed histologic diagnosis in order to refine and better establish the diagnosis of idiopathic MN. This study will compare the PLA2R Ac diagnosis in patients with lupus MN (class V) and focal segmental glomeruloesclerosis patients. In addition, this study will correlate PLA2R Ac serum levels in MN patients with the degree of proteinuria and disease activity.Therefore, this study aims to develop and establish the serum and tissue diagnosis with the PLA2R Ac tests in idiopathic MN patients, allowing an earlier diagnosis which may prevent further investigation and additional costs in the search for secondary causes of membranous nephropathy. Furthermore, there is no study performed with latin population, most studies were done using caucasian or asian population. (AU)