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

Area of Science:

• Nephrology
• Immunology
• Clinical Trials

Background:

• Membranous nephropathy (MN) linked to anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies is a primary cause of nephrotic syndrome globally.
• Current treatments for anti-PLA2R MN are often empirical and associated with significant side effects.
• Understanding the disease has advanced, but effective targeted therapies are still needed.

Purpose of the Study:

• To evaluate the efficacy and safety of selective immunoadsorption for removing pathogenic anti-PLA2R autoantibodies in adult patients with biopsy-proven anti-PLA2R MN.
• To assess the impact of immunoadsorption on anti-PLA2R antibody titers, proteinuria, renal function, serum albumin, and quality of life.

Main Methods:

• A multicenter, single-arm prospective clinical trial involving 12 adult patients with anti-PLA2R MN.
• Patients underwent five sessions of peptide GAM immunoadsorption.
• Follow-up assessments for primary and secondary outcomes were conducted over 12 months, including stratification by the HLA-DQA1*05 high-risk allele.

Main Results:

• Immunoadsorption significantly reduced anti-PLA2R autoantibody titers at week 2 (P=.023) and week 52 (P=.017).
• The therapy was safe and well-tolerated, with significant improvement in serum albumin levels (P<.001).
• No significant changes were observed in proteinuria or renal function; however, patients with the high-risk allele showed promising anti-PLA2R titer reduction.

Conclusions:

• Immunoadsorption therapy is a safe and well-tolerated treatment option for anti-PLA2R positive autoimmune membranous nephropathy.
• The procedure effectively lowers pathogenic autoantibody levels and improves serum albumin.
• Further research may explore its potential benefits in specific patient cohorts, such as those with the high-risk HLA-DQA1*05 allele.