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Kidney Week

Abstract: TH-PO0779

THSD7A-Positive Membranous Nephropathy (MN) in a Patient with Neurosarcoidosis: Expanding the Spectrum of Autoimmune-Associated MN

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Patel, Jaymin Bakul, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
  • Smith, Zachary, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
  • Warner, David M., University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
  • Drenkhahn, Jane E., Cincinnati VA Medical Center, Cincinnati, Ohio, United States
  • Gudsoorkar, Prakash Shashikant, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
Introduction

Membranous nephropathy (MN) is increasingly recognized as a heterogeneous disease defined by distinct target antigens. Thrombospondin type-1 domain-containing 7A (THSD7A)-associated MN is classically linked with malignancy (6% to 25%), though emerging evidence suggests autoimmune associations. We present a diagnostically complex case of THSD7A-positive MN in a patient with neurosarcoidosis (NS), underscoring the expanding spectrum of secondary MN etiologies.

Case Description

A 55-year-old African American male with a history of NS presented with nephrotic syndrome. NS was diagnosed in 2021 after he developed transverse myelitis; lymph node biopsy confirmed noncaseating granulomas. Kidney biopsy in October 2024 showed immune complex-mediated MN with mild chronicity and moderate arteriosclerosis. Immunofluorescence revealed granular capillary wall staining, and electron microscopy showed subepithelial deposits.
Serologies were negative for anti-PLA2R (Phospholipase A2 Receptor) antibodies but positive for anti-THSD7A antibody (1:160). Given the known malignancy association with THSD7A, extensive oncologic screening was performed: CT chest/abdomen/pelvis, PET-CT, and colonoscopy were all negative. 385-gene panel was unrevealing.
In the absence of malignancy and with ongoing immune dysregulation, rituximab was selected for dual efficacy in MN and NS and is starting on May 23rd 2025. Clinical and serological monitoring will occur.

Discussion

This case adds to the growing recognition that THSD7A-positive MN arises in the context of autoimmune diseases. Recent literature by Sethi et al., notes similar associations in sarcoidosis. Incorporating clinical context, antigen subtyping, and histopathology when evaluating THSD7A-positive MN is essential. This case also highlights the possible role of rituximab as a targeted therapy bridging glomerular and neurologic autoimmune disease.

Digital Object Identifier (DOI)