Abstract: TH-PO0751
HTRA1 Is a Common Autoantigen in Membranous Nephropathy in Very Elderly Patients
Session Information
- Glomerular Histopathology: Evolving Insights
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Al-Rabadi, Laith, University of Utah Health, Salt Lake City, Utah, United States
- Storey, Aaron J., Arkana Laboratories, Little Rock, Arkansas, United States
- Ibrahim, Abdelrahman, University of Utah Health, Salt Lake City, Utah, United States
- Nwaduru, Chinedu Elvis, University of Utah Health, Salt Lake City, Utah, United States
- Beck, Laurence H., Boston University, Boston, Massachusetts, United States
- Caza, Tiffany, Arkana Laboratories, Little Rock, Arkansas, United States
Background
We recently identified the serine protease HTRA1 as an antigen in membranous nephropathy (MN), an autoimmune disease with immune complexes limited to glomeruli. In patients with MN, age-appropriate cancer screening is mandated, especially in elderly patients, given the association between cancer and MN. HTRA1 has been known to be a tumor suppressor protein in several types of cancer. We have observed an increased frequency of HTRA1 MN in older individuals and examined disease associations.
Methods
We performed paraffin immunofluorescence staining for HTRA1 in a cohort of very elderly patients (≥80 years old) with PLA2R-negative MN to determine the frequency of HTRA1-positive MN in an elderly population. In a comparison cohort, we examined the overall frequency of HTRA1-positive MN in a consecutive series of 157 cases of PLA2R/THSD7A/NELL1/EXT-negative MN of all ages assessed by mass spectrometry.
Results
HTRA1 positivity was found in 12 of 54 (22.2%) consecutive patients with MN ≥ 80 years of age, compared to 4 of 157 (2.5%) in a consecutive series of PLA2R/THSD7A/EXT1/NELL1-negative MN of a general population. Among HTRA1 patients (in both cohorts), the mean age was 81.4 ± 6.8 years and there was a male predominance (75%). The mean serum creatinine was 1.7 ± 0.7 mg/dL and 14 had nephrotic range proteinuria (87.5%). Two had active malignancy (12.5%), including one with prostate cancer and one with metastatic lung cancer. Concurrent pathology was identified in seven patients, including four with concurrent acute tubular injury, two with diabetic nephropathy, and one with ALECT2 amyloidosis.
Among the remaining (n=42) patients in this cohort who HTRA1- (and PLA2R-) negative, there was also male predominance (66.7%), mean creatinine was 1.9 ± 1.2 mg/dL and the majority had nephrotic range proteinuria (88.9% with available data). Two patients had malignancy, one with lymphoma and one with breast cancer. Concurrent diabetic nephropathy was seen in 9 patients.
While HTRA1 had a higher prevalence in the very elderly, we found that PLA2R was somewhat underrepresented in patients ≥ 80 years of age (44.4% of all MN cases).
Conclusion
HTRA1-positive MN is highly enriched in the very elderly population (8.9-fold increase compared to a general population of MN patients). It is unclear whether it is enriched in patients with malignancy.