Serine protease HTRA1 is a common autoantigen in membranous nephropathy in patients of 80 years and older.
| Title: | Serine protease HTRA1 is a common autoantigen in membranous nephropathy in patients of 80 years and older. |
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| Authors: | Al-Rabadi LF; Division of Nephrology, University of Utah Health, Salt Lake City, Utah, USA. Electronic address: laith.al-rabadi@hsc.utah.edu.; Storey AJ; Arkana Laboratories, Little Rock, Arkansas, USA.; Abuelsamen T; Division of Nephrology, University of Utah Health, Salt Lake City, Utah, USA.; Takayama S; Division of Nephrology, University of Utah Health, Salt Lake City, Utah, USA.; Walker PD; Arkana Laboratories, Little Rock, Arkansas, USA.; Nwaduru CE; Division of Nephrology, University of Utah Health, Salt Lake City, Utah, USA.; Kawalit I; International Renal Care Association, Amman, Jordan.; Zimmerman M; Division of Nephrology, University of Utah Health, Salt Lake City, Utah, USA.; Hoxha E; Department of Medicine, University Hospital Würzburg, Würzburg, Germany.; Borza DB; Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA.; Beck L Jr; Division of Nephrology, Boston Medical Center, Boston, Massachusetts, USA.; Larsen CP; Arkana Laboratories, Little Rock, Arkansas, USA.; Caza TN; Arkana Laboratories, Little Rock, Arkansas, USA. Electronic address: tiffany.caza@arkanalabs.com. |
| Source: | Kidney international [Kidney Int] 2026 Jun; Vol. 109 (6), pp. 1318-1323. Date of Electronic Publication: 2026 Mar 27. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 0323470 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-1755 (Electronic) Linking ISSN: 00852538 NLM ISO Abbreviation: Kidney Int Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2016- : New York : Elsevier; Original Publication: New York, Springer-Verlag. |
| MeSH Terms: | Glomerulonephritis, Membranous*/immunology ; Glomerulonephritis, Membranous*/pathology ; Glomerulonephritis, Membranous*/diagnosis ; Glomerulonephritis, Membranous*/blood ; High-Temperature Requirement A Serine Peptidase 1*/immunology ; High-Temperature Requirement A Serine Peptidase 1*/analysis ; Autoantigens*/immunology ; Autoantigens*/analysis; Receptors, Phospholipase A2/immunology ; Receptors, Phospholipase A2/analysis ; Autoantibodies/blood ; Humans ; Male ; Aged, 80 and over ; Female ; Age Factors |
| Abstract: | Introduction: Membranous nephropathy (MN) in very elderly patients frequently remains antigen-negative after routine testing, limiting diagnostic precision. Recently, serine protease high temperature requirement protein A1 (HTRA1) has been identified as a novel MN autoantigen. Here, we focused on patients 80 years and older with MN and sought to systematically evaluate this association.; Methods: Three cohorts of patients with MN were examined under institutional approval, including 157 consecutive all-age series of PLA2R/THSD7A/NELL1/EXT1-negative patients with MN typed by mass spectrometry; 54 PLA2R-negative MN in patients aged 80 years and older assessed by paraffin immunofluorescence; and 45 PLA2R-negative malignancy-associated patients with MN. HTRA1 positivity was determined by paraffin immunofluorescence and/or mass spectrometry. Clinical and histopathologic features were reviewed where available. Proportions were compared using Fisher's exact test.; Results: HTRA1 positivity was identified in 1.9% of patients with PLA2R/THSD7A/NELL1/EXT-negative MN, 22.2% of patients 80 years and older, and 6.7% of patients with PLA2R-negative malignancy-associated MN. Compared with the all-age antigen-negative cohort, HTRA1 positivity was significantly enriched in patients aged 80 years (relative risk 11.6; 95% confidence interval 3.4- 39.7). Across all 18 HTRA1-positive cases, mean age was 81.5, 66.7% were male, and 83.3% had nephrotic-range proteinuria.; Conclusions: HTRA1 is a common autoantigen in PLA2R-negative MN among very elderly patients, occurring in approximately one in five cases aged 80 years or more. These findings support inclusion of HTRA1 testing in diagnostic evaluation of antigen-negative MN in patients 80 years and older and suggest the existence of an age-linked MN subtype.; (Copyright © 2026 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.) |
| Contributed Indexing: | Keywords: HTRA1; antigen; case series; kidney biopsy; membranous nephropathy |
| Substance Nomenclature: | EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HTRA1 protein, human); 0 (Autoantigens); 0 (Receptors, Phospholipase A2); 0 (PLA2R1 protein, human); 0 (Autoantibodies) |
| Entry Date(s): | Date Created: 20260329 Date Completed: 20260521 Latest Revision: 20260521 |
| Update Code: | 20260522 |
| DOI: | 10.1016/j.kint.2026.02.036 |
| PMID: | 41905594 |
| Database: | MEDLINE |
Journal Article