Abstract: TH-PO1098
Protocadherin 7-Associated Membranous Nephropathy: A Series of 10 Cases
Session Information
- Pathology and Lab Medicine
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1700 Pathology and Lab Medicine
Authors
- Caza, Tiffany, Arkana Laboratories, Little Rock, Arkansas, United States
- Storey, Aaron J., Arkana Laboratories, Little Rock, Arkansas, United States
- Stephens, Owen W., Arkana Laboratories, Little Rock, Arkansas, United States
- Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States
Background
Protocadherin 7 (PCDH7) was recently identified as an autoantigen in membranous nephropathy (MN) with fewer than 20 cases reported to date. Here, we describe clinicopathologic features from a cohort of 10 patients with PCDH7-positive MN.
Methods
Protein A/G immunoprecipitation, followed by mass spectrometry (MS) was performed on 158 PLA2R/THSD7A/NELL1/EXT-quadruple negative MN biopsies, as well as 66 cases of membranous lupus nephritis (MLN) for antigen identification. PCDH7 status was confirmed by immunohistochemistry. Histopathologic and clinical characteristics were examined by review of biopsy reports and medical records.
Results
Ten of 158 (6.3%) of PLA2R/THSD7A/NELL1/EXT-quadruple negative MN and zero MLN biopsies were PCDH7-positive. Two cases were of dual antigen type (20%), with one PLA2R/PCDH7 and one CNTN1/PCDH7-positive. Five had a second biopsy diagnosis, including diabetic glomerulosclerosis (n=3), plasma cell rich interstitial nephritis (n=1), and crescentic glomerulonephritis (n=1).
The mean age of PCDH7-positive patients was 60.0 ± 19.4 years, and there was a male predominance (80%). Clinical co-morbidities were common, including hypertension (n=6), diabetes (n=5) , cirrhosis (n=2), monoclonal gammopathy (n=2), and malignancy (n=1). Mean serum creatinine and proteinuria were 2.3 ± 1.0 mg/dL and 2.3 ± 2.5 g/g, respectively. Serologic studies were notable for anti-nuclear antibodies in 5 patients, anti-neutrophil cytoplasmic antibodies in 1 patient, SSA/B antibodies in 2 patients, and one was positive for Hepatitis B virus.
By light microscopy, seven cases showed mesangial expansion, eight had segmental sclerosis, and two contained crescents. Immunofluorescence showed 1+ or greater positivity for IgA in 2, IgM in 7, and 1 was C1q positive. C3 staining was absent or weak, with 8/10 patients having ≤1+ positivity. Electron microscopy demonstrated severe podocyte foot process effacement in 90%, all with stage III deposits.
Conclusion
PCDH7 was identified as an autoantigen of 6.3% of cases of PLA2R/THSD7A/NELL1/EXT-negative MN and predominantly impacted older males with frequent co-morbidities. Further data is required to identify whether distinct clinical associations exist with this type of MN.
Funding
- NIDDK Support