Abstract: TH-PO960
Dupilumab and Primary Membranous Nephropathy
Session Information
- Glomerular Trainee Case Reports
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Greco, Jessica M., Ohio State Wexner Medical Center, Columbus, Ohio, United States
- Arora, Swati, Allegheny Health Network, Pittsburgh, Pennsylvania, United States
- Sopkovich, Jennifer, The Ohio State Wexner Medical Center, Gahanna, Ohio, United States
- Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Introduction
Primary membranous nephropathy (MN) is an immune complex-mediated disease. In most cases patients develop autoantibodies to the phospholipase A2 receptor (PLA2R), often of IgG4 subclass. Effective immunosuppressive treatment of MN results in a decline in anti-PLA2R that precedes clinical resolution of the disease. We recently saw a patient who had PLA2R-positive MN that did not have a durable response to multiple therapies. She had severe atopic dermatitis that was treated with dupilumab, an interleukin-4 (IL-4) receptor antagonist. After dupilumab was started the nephrotic syndrome resolved.
Case Description
A 21 year-old female with a history of asthma and severe atopic dermatitis since childhood presented with nephrotic syndrome. A kidney biopsy showed PLA2R-positive MN. The Figure shows treatments, immunologic responses, and clinical responses over time. Despite significant immunosuppression her eczema persisted and worsened so dupilumab was started. Within 2 months of initiating dupilumab the anti-PLA2R levels decreased, albumin normalized, and the nephrotic syndrome resolved.
Discussion
MN, an autoimmune disease that involves activation of T-follicular helper cells and B cells. Several pro-inflammatory cytokines are increased in the urine and serum of patients with MN, including IL-4. IL-4 promotes B cell isotype switching to IgG4, differentiation of naïve T-helper cells to Th2 cells, and inhibits the differentiation of Th1 cells. Th2 cells then release IL-4 leading to a positive feedback loop. MN is characterized histologically by IgG4-dominant subepithelial immune complexes. Dupilumab is a human monoclonal antibody that blocks the IL-4 alpha receptor, inhibiting the effects of IL-4 and IL-13. IL-4 blockade in MN may help attenuate anti-PLA2R IgG4 antibody production, and combined with traditional immunosuppression treat refractory MN. Further prospective studies are warranted to define the role of IL-4 antagonism in the management of MN.