Anti-Phospholipase A2 Receptor in Nonlupus Patients with Membranous Nephropathy and Crescents

Yiqin Zuo; Livia Barreira Cavalcante; James Monroe Smelser; Neil Sanghani; Jamie P Dwyer; Julia Breyer Lewis; Agnes B Fogo

doi:10.1159/000520641

Anti-Phospholipase A2 Receptor in Nonlupus Patients with Membranous Nephropathy and Crescents

Glomerular Dis. 2021 Nov 2;2(2):75-82. doi: 10.1159/000520641. eCollection 2022 Apr.

Authors

Yiqin Zuo^{1

2}, Livia Barreira Cavalcante³, James Monroe Smelser⁴, Neil Sanghani⁵, Jamie P Dwyer⁵, Julia Breyer Lewis⁵, Agnes B Fogo^{1

6

7}

Affiliations

¹ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
² Department of Pathology and Laboratory Medicine, University of Miami, Miami, Florida, USA.
³ Pathology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
⁴ Huntsville Renal Clinic PC, Huntsville, Alabama, USA.
⁵ Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁶ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷ Division of Pediatric Nephrology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Abstract

Introduction: Anti-phospholipase A2 receptor (PLA2R) is detected in approximately 70% of biopsies of "primary" membranous nephropathy (MN). Crescents in MN in nonlupus patients suggest additional injury, such as antineutrophil cytoplasmic antibody (ANCA) or anti-glomerular basement membrane (anti-GBM)-associated glomerulonephritis and are postulated to reflect injury by a mechanism that unmasks cryptic epitopes leading to the second autoantibody.

Methods: We studied PLA2R staining in nonlupus patients with MN and crescents. Native renal biopsies in 16 nonlupus patients with MN and crescents were stained for PLA2R.

Results: The patients included 5 women and 11 men, with mean age 61 years and elevated serum creatinine (mean 4.68 mg/dL). Hematuria and proteinuria (mean 4.97 g/day) were documented in 13 patients. Two patients had positive serum anti-GBM antibody. Nine of 11 patients tested for ANCA were positive, with p-ANCA (n = 4), c-ANCA (n = 2), or both (n = 1), with 2 not specified. On average, 27% of glomeruli had crescents. One patient had an initial biopsy with MN, 4 years later had MN with crescent, and 7 years later had rebiopsy with persistent MN with crescents. One patient had ANCA-associated vasculitis, and 5 years later had MN and crescent. The remaining 14 patients had concurrent diagnoses of MN and crescents. PLA2R was positive in 5 cases, 3 with ANCA positivity, 2 with unknown ANCA status, and none with anti-GBM disease. The patient with initial MN preceding crescent was PLA2R positive; the patient with initial ANCA-associated vasculitis preceding MN was PLA2R negative.

Conclusions: Most patients (64%) presented with concomitant MN and crescents, with rare occurrence of an initial disease process followed later by the second injury. PLA2R was positive in 31% of patients, suggesting most are secondary MN. Further study to determine the cryptic epitopes may shed light on the triggering mechanisms for these rare but unlikely coincidental glomerular injuries.

Keywords: Anti-phospholipase A2 receptor; Crescents; Membranous nephropathy.

Grants and funding

This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.