Renal expression of PLA2R and NELL-1 autoantigens in a coorte of Membranous Nephropathy patients: Impact in the prognostics and tratment response.

• Grant number: 24/12987-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Irene de Lourdes Noronha
• Grantee: Camila Takahashi Granadi
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Membranous nephropathy (MN) is an insidious glomerular disease caused by the deposition of immune complexes, leading to the impairment of glomerular filtration barrier and to the development of nephrotic syndrome. This condition can both progressively evolve to chronic kidney loss of function or go into spontaneous remission, depending on the case. MN is classified into primary and secondary forms: In primary MN, patients have circulating autoantibodies against PLA2R1 autoantigens, expressed endogenously by their podocytes, causing glomerular autoimmune inflammation. On the other hand, as suggested by the name, the secondary form of MN is secondary to other diseases and usually occurs due to the accumulation of subepithelial immune complexes, formed by circulating antibodies bound to GBM planted antigens. MN can be indirectly suggested by the presence of high proteinuria in urine analysis along with positive serum ELISA tests for the presence of circulating anti-PLA2R1 autoantibody. However, MN diagnostics can only be securely achieved by renal biopsy analysis, which provides precise information on the glomerular damage degree and the renal histological impairment. Moreover, it is possible to directly investigate the presence of podocyte PLA2R1 antigen in renal biopsies, through immunohistochemistry (IHC), applying recently described specific monoclonal antibodies. The main aim of the present study is to investigate the renal expression of PLA2R1 antigen by IHC in renal biopsies from a cohort of 75 patients with both primary or secondary MN forms. We intend to correlate PLA2R1 IHC positivity to clinical and laboratorial features, as well as to the patient response to the employed treatment.