Immune-Monitoring Disease Activity in Primary Membranous Nephropathy

Frontiers in Medicine

article

Paolo Cravedi¹  Marta Jarque²  Andrea Angeletti³  Àlex Favಠ Chiara Cantarelli⁴  Oriol Bestard² 

[1] Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, United States;Experimental Nephrology Laboratory, Biomedical Research Institute of Bellvitge (IDIBELL);Dialysis and Renal Transplant Unit, Department of Experimental Diagnostic and Specialty Medicine (DIMES), St. Orsola Hospital, University of Bologna;Dipartimento di Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Parma;Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona University, Biomedical Research Institute of Bellvitge (IDIBELL)

关键词: membranous nephropathy;    glomerulonephritis recurrence;    PLA 2 R;    THSD7A;    autoreactive B cells;   

DOI  :  10.3389/fmed.2019.00241

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Primary membranous nephropathy (MN) is a glomerular disease mediated by autoreactive antibodies, being the main cause of nephrotic syndrome among adult patients. While the pathogenesis of MN is still controversial, the detection of autoantibodies against two specific glomerular antigens, phospholipase A2 receptor (PLA 2 R) and thrombospondin type 1 domain containing 7A (THSD7A), together with the beneficial effect of therapies targeting B cells, have highlighted the main role of autoreactive B cells driving this renal disease. In fact, the detection of PLA 2 R-specific IgG4 antibodies has resulted in a paradigm shift regarding the diagnosis as well as a better prediction of the progression and recurrence of primary MN. Nevertheless, some patients do not show remission of the nephrotic syndrome or do rapidly recur after immunosuppression withdrawal, regardless the absence of detectable anti-PLA 2 R antibodies, thus highlighting the need of other immune biomarkers for MN risk-stratification. Notably, the exclusive evaluation of circulating antibodies may significantly underestimate the magnitude of the global humoral memory immune response since it may exclude the role of antigen-specific memory B cells. Therefore, the assessment of PLA 2 R-specific B-cell immune responses using novel technologies in a functional manner may provide novel insight on the pathogenic mechanisms of B cells triggering MN as well as refine current immune-risk stratification solely based on circulating autoantibodies.

【 授权许可】

CC BY