Background And Objectives: Thrombospondin type-I domain-containing 7A (THSD7A) was recently identified as the target antigen in about 10% of patients with M-type phospholipase A2 receptor (PLA2R)-negative membranous nephropathy in European and North American populations. The prevalence of THSD7A in other populations and their clinical associations deserve further clarification.
Design, Setting, Participants, & Measurements: Immunofluorescence assay was performed to investigate anti-THSD7A antibodies in 578 consecutive patients with biopsy-proven idiopathic membranous nephropathy, 114 patients with secondary membranous nephropathy, 64 disease controls, and 20 healthy controls. Glomerular expression of THSD7A antigen was examined by immunohistochemistry. Anti-PLA2R antibodies and glomerular PLA2R expression were also screened.
Results: Among the 578 patients with idiopathic membranous nephropathy, 12 (2%) patients were identified as THSD7A-positive: ten patients were THSD7A-positive alone, which accounted for 16% (ten of 64) of PLA2R-negative patients; two patients were dual-positive for both anti-THSD7A and anti-PLA2R antibodies and showed enhanced expression of both antigens colocalized in glomeruli. Among the 114 patients with secondary membranous nephropathy, one among 44 (2%) patients with cancer had anti-THSD7A antibodies, whereas 18 of 44 (41%) had anti-PLA2R antibodies. No anti-THSD7A antibody was detected in other disease controls or healthy individuals. Clinical features were comparable between the patients with and without THSD7A. During follow-up, two patients who achieved remission had a clearance of circulating antibodies against THSD7A, whereas antibodies increased in parallel with proteinuria in a patient with a relapse.
Conclusions: THSD7A-associated membranous nephropathy has a low prevalence in Chinese patients. The double-positive patients suggest dual autoimmune responses.
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http://dx.doi.org/10.2215/CJN.01460217 | DOI Listing |
J Pak Med Assoc
January 2025
Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan.
Objectives: To analyse the aetiological spectrum, clinical presentation and short-term renal outcomes of patients with acute kidney injury of uncertain aetiology subjected to percutaneous renal biopsy.
Methods: The prospective, cohort study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, from March 1 to October 30, 2024, and comprised hospitalised acute kidney injury patients of either gender aged 18- 75 years who had been subjected to percutaneous renal biopsy. The patients were followed up for at least three months from the time of the biopsy.
Nephrol Dial Transplant
January 2025
Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Manchester, UK.
Background And Hypothesis: The PLA2R antibody test is a valuable first-line diagnostic tool for primary membranous nephropathy (MN), helping to identify PLA2R-related MN and potentially eliminating the need for a kidney biopsy in some individuals. By reducing the reliance on biopsies, the test streamlines diagnosis and improves patient care. However, determining the optimal PLA2R measurement method and cut-off is critical to maximising the benefits of the test and minimising any harms.
View Article and Find Full Text PDFBackground: With the increasing prevalence of membranous nephropathy (MN), the gut microbiome (GM) is increasingly implicated in its cause, yet the intricate mechanisms remain unclear. Whether changes in the diversity and richness of gut microbial populations among MN patients contribute to disease prevalence is still unanswered, necessitating further exploration into the potential causative link between the GM and MN.
Methods: We conducted a comprehensive bidirectional Mendelian randomization (MR) study.
Am J Physiol Renal Physiol
January 2025
Department of Medicine, Boston Medical Center and Department of Medicine, Boston University. Chobanian & Avedisian School of Medicine.
Transcriptomic analysis of microdissected human glomeruli has suggested novel molecular signatures associated with MN by revealing several genes differentially upregulated in MN compared to other glomerular diseases. We focused on a novel protein, Family with sequence similarity 114 member A1 (FAM114A1) that was identified as the top classifier gene in the dataset. To determine the localization of FAM114A1 within glomeruli, we performed immunofluorescence (IF) staining on normal human kidney specimens.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Shanxi Genetic Engineering Center for Experimental Animal Models, The Fifth Hospital (Shanxi Provincial People's Hospital) of Shanxi Medical University, Taiyuan, Shanxi, China.
Phospholipase A2 receptor 1 (PLA2R1) exists in many animals and plays an important role in membranous nephropathy. In this study, we aimed to evaluate a PLA2R1 knock-in rat model with repaired kidney function to study the molecular mechanisms of membranous nephropathy. We constructed the PLA2R1 knockout [PLA2R1(-)] model and PLA2R1 knock in [PLA2R1(+)] model in rats.
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