Aims Phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as pathogenic antigens in patients with membranous nephropathy (MN). Notably, PLA2R is detected in few patients with malignancy-associated MN, and a high incidence of cancer is reported in patients with THSD7A-associated MN. Therefore, the roles of PLA2R and THSD7A in malignancy-associated MN must be clarified.
Methods Serum anti-PLA2R antibodies and glomerular PLA2R staining were assessed in 36 patients with malignancy-associated MN, followed by examination of serum anti-THSD7A antibodies and glomerular THSD7A. THSD7A staining in cancer tissues was also assessed in 9 of the 36 patients.
Results Twelve (33%) of 36 patients were positive for both glomerular PLA2R and serum anti-PLA2R antibodies, one of whom had enhanced glomerular THSD7A staining. Two patients were positive for either glomerular PLA2R or serum anti-PLA2R antibody. All these patients had IgG4-dominant deposits in glomeruli. Among the 22 (61%) patients who were double negative for glomerular PLA2R and serum anti-PLA2R antibodies, 17 of 20 (85%) had IgG1-dominant deposits in glomeruli, and 2 (9.1%) were positive for glomerular THSD7A staining. Serum anti-THSD7A antibody was not detected in any of the 36 patients. Among the nine patients with available cancer tissues, positive staining of THSD7A in the cancer tissues was observed in five (56%) patients, and one showed enhanced glomerular staining of THSD7A.
Conclusions Screening of glomerular PLA2R antigen and serum anti-PLA2R antibodies is necessary in patients with malignancy-associated MN, whereas the incidence of glomerular THSD7A antigen or circulating anti-THSD7A antibodies is uncommon.
- membranous nephropathy
- igg subclasses
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Handling editor Dhirendra Govender.
Contributors Research conception and study design: ZL and CZh. Research and data analysis: CZh, MZ, DC and QR. Manuscript preparation: CZh and ZL. Clinical data collection: CZh, WX and WQ. Pathological scoring: CZ and MZ. Research sample preparation: CZh and MZ. All authors have read the journal’s authorship agreement and agree with the statements. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Disclaimer The funders of this study were not involved in the study design, in the collection, analysis and interpretation of the data, in the writing of the report and in the decision to submit the article for publication.
Competing interests None declared.
Patient consent for publication Obtained.
Ethics approval This study was approved by the Ethics Committee of Jinling Hospital in accordance with the Declaration of Helsinki.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information.