Phospholipase A2 Receptor Associated Membranous Nephropathy as the Initial Manifestation of Systemic Lupus Erythematosus

Dear Editor,

Although the M-type phospholipase A2 receptor (PLA2R) associated membranous nephropathy (MN) is typically primary,¹ it can occur secondary to autoimmune diseases. MN in systemic lupus erythematosus (SLE) typically has exostocin-1/exostocin-2 as target antigens followed by NELL1 and NCAM1.¹ Emerging evidence implicates PLA2R with lupus-MN. Garcia-Vives et al. demonstrated circulating anti-PLA2R in 18.9% of lupus-MN.² Another study reported PLA2R-associated primary-MN preceding subsequent SLE development.³

A 43-years-old lady presented with nephrotic syndrome, acute kidney injury, normal serum complements, positive ANA (1:1000), negative dsDNA antibody, and Coombs-negative anemia. She met no other classification criteria for SLE. A kidney biopsy revealed MN, acute tubular injury, and granular IgG (3+), C3 (2+), and C1q (1+) deposits along capillary loops. PLA2R was detectable in the biopsy and serum (26 RU/mL).

The patient fulfilled the 2019 EULAR/ACR⁴ entry criterion for SLE with a positive ANA ≥ 1:80. Lupus-MN in a kidney biopsy conferred a score of 8, short of the minimum score of 10 required for SLE classification. Further, the absence of a full-house repertoire on biopsy and the presence of circulating/tissue PLA2R antibodies were atypical of lupus-MN. Therefore, at the first presentation, this patient met the ANA entry criterion for SLE but did not reach the 10-point threshold.

This patient was risk stratified (2021-KDIGO guidelines)⁵ and initiated on cyclical cyclophosphamide/steroid treatment. She defaulted and presented 6 months later with worsening proteinuria, new-onset leukopenia, and pleuritic chest pain. With these new findings, she fulfilled the 2019-EULAR/ACR classification criteria for SLE, accruing a score of 11. This case suggests that PLA2R associated MN may precede the clinical evolution of SLE. Antigen typing alone cannot distinguish primary from lupus-MN and must be integrated with clinical, serologic, and histologic features.