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Kidney Week

Abstract: SA-PO865

FSGS in an Adult Transplant Recipient Possibly Linked to a New Antibody against WT1

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Wei, Khaing San, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Herzog, Christian, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Bhusal, Sushma, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Arthur, John M., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
Introduction

Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of glomerular injury primarily affecting the glomerular podocytes, characterized by segmental scarring of select glomeruli. Primary FSGS involves circulating factors and can recur after transplant.

Case Description

A 66-year-old female with PMH of hypertension, microscopic hematuria, CKD diagnosed at the age of 30 progressed to ESKD at age 58 requiring HD. She had minimal proteinuria prior to ESKD. Her native biopsy contained only a single glomerulus but revealed thin basement membranes with podocyte effacement. She underwent DDKT at age 61. She had immediate graft function with UPCR of 0.67 mg/mg. Proteinuria resolved (UPCR undetectable) after one year but she again developed proteinuria of 2.1 g at 16 months and 11 g at 18 months. Her eGFR was 19-22 ml/min and serum albumin 3.2g/dl. An allograft biopsy showed FSGS with some collapsing features. Genetic analysis revealed a WT1 gene mutation (Ser466Phe). She underwent regular therapeutic plasma exchange (TPE) with stable Cr levels at 1.8 -2.2 mg/dl and UPCR at 2.0mg/mg. Plasma was collected prior to the first TPE.
We performed western blot analysis using her plasma as the source of the primary antibody to determine if she could have an antibody against WT1. Normal human glomerular lysates were separated, transferred to PVDF and incubated with sera of the FSGS patient and two controls. Western blots were probed with secondary Ab against human IgA, IgG/M, IgM and developed with ECL reagent. A strong band at about 50kDa detected in the patient serum probed with anti IgM but not with IgG or IgA, suggested the presence of an antibody against WT1. The band was not present in two control plasma samples.

Discussion

The presence of an antibody that recognizes a glomerular protein at about 50 kDa suggests that this patient could have developed an autoantibody against WT1 after transplantation. Since the patient’s kidney expressed a different sequence of WT1, this would be a novel antigen to her immune system. Since WT1 is expressed on podocytes, this antibody could interfere with the glomerular permeability barrier. Disease causing antibodies against nephrin have been described in children with nephrin mutations after kidney transplantation.