Peptide GAM immunoadsorption in anti-PLA2 R positive autoimmune membranous nephropathy. The PRISM trial

Patrick Hamilton, Durga Kanigicherla, Prasanna Hanumapura, Kieran Blaikie, James Ritchie, Smeeta Sinha, Paul Brenchley, Sandip Mitra

Research output: Contribution to journalArticlepeer-review

Abstract

Membranous nephropathy associated with anti-PLA 2R autoantibody is a significant cause of nephrotic syndrome worldwide. Treatment remains empiric with a significant side-effect burden despite an increase in our understanding of the disease. We studied the effect of selectively removing this pathogenic autoantibody using immunoadsorption in adult patients with biopsy proven anti-PLA 2R membranous nephropathy. This was a multicenter, single-arm prospective clinical trial carried out in the United Kingdom. Twelve patients underwent five consecutive sessions of peptide GAM immunoadsorption with 12 months follow-up. Primary outcome was anti-PLA 2R titer at week 2. Secondary outcomes were safety and tolerability of therapy, antibody profile, and change in proteinuria, renal excretory function, serum albumin, total immunoglobulin, and quality of life at weeks 12, 24, and 52. Patients were also stratified by the presence or absence of the high-risk allele (heterozygous or homozygous for HLA-DQA1*05). Median pretreatment anti-PLA 2R was 702.50 U/mL, 1045.00 U/mL at week 2 (P-value.023) and 165.00 U/mL at week 52 (P-value.017). The treatment was well tolerated and safe. Two patients required rescue immunosuppression during the follow-up period. There was a significant improvement in serum albumin with a median at baseline of 20.50 g/L rising to 25.00 g/L at week 52 (P-value <.001). There was no statistical difference over the follow-up period in proteinuria or renal function. Patients in possession of a high-risk allele saw improvement in anti-PLA 2R titers, possibly representing a cohort more likely to benefit from immunoadsorption. Immunoadsorption therapy is a safe treatment and well-tolerated treatment in anti-PLA 2R positive autoimmune membranous nephropathy.

Original languageEnglish
Pages (from-to)40-53
Number of pages14
JournalJournal of Clinical Apheresis
Volume37
Issue number1
Early online date2 Feb 2022
DOIs
Publication statusPublished - 2 Feb 2022

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies/blood
  • Autoimmune Diseases/therapy
  • Female
  • Glomerulonephritis, Membranous/blood
  • Humans
  • Male
  • Middle Aged
  • Peptides
  • Plasmapheresis/methods
  • Prospective Studies
  • Receptors, Phospholipase A2/immunology

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