Bortezomib Treatment for Refractory PLA2R-Positive Membranous Nephropathy.

Area of Science:

• Nephrology
• Immunology
• Internal Medicine

Background:

• Membranous nephropathy (MN) is a leading cause of nephrotic syndrome.
• Anti-phospholipase A2 receptor (PLA2R) antibodies are implicated in PLA2R-positive MN.
• B-cell depletion therapies are standard but not universally effective.

Observation:

• A patient with PLA2R-positive MN showed resistance to B-cell depletion, plasmapheresis, and cyclophosphamide.
• This patient achieved rapid immunologic remission after treatment with bortezomib, a proteasome inhibitor.

Findings:

• The patient's refractory disease suggests B-cell depletion alone may be insufficient.
• The success of bortezomib points to plasma cells as a potential source of pathogenic anti-PLA2R antibodies.

Implications:

• This case underscores the need to consider alternative antibody-producing cells in MN.
• Targeting plasma cells may offer a novel therapeutic strategy for refractory MN.
• Individualized treatment approaches based on antibody production source are crucial for improving patient outcomes.