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Original

Development of autoimmune antibodies against human phospholipase A2 receptor and the application as diagnostic criteria for primary membranous nephropathy 

Shukun Wu, Yixing Zhai, Na Yang, Zhou Zhou, Yingchun Huang, Li Yang, Bing Lai, and Guisen Li

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Volume 104 (2025) p. 390 - 400

Abstract

Clinical Nephrology, Vol. 104 – No. 6/2025 (390-400)

Development of autoimmune antibodies against human phospholipase A2 receptor and the application as diagnostic criteria for primary membranous nephropathy 

Shukun Wu¹*, Yixing Zhai²*, Na Yang², Zhou Zhou³, Yingchun Huang², Li Yang², Bing Lai², and Guisen Li¹

¹Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, ²Department of Biological Products, Institute of Drug Development, Chengdu Di’ao Pharmaceutical Group Co., Ltd., and ³Department of Gastroenterology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Introduction: Membranous nephropathy (MN) is a severe chronic kidney disease (CKD) with ~ 30% of patients progressing to end-stage renal disease within 10 years. Phospholipase A2 receptor (PLA2R) is one of the major target antigens of MN. Despite the importance of PLA2R antibodies in the pathogenesis, diagnosis, and prognosis of MN, anti-human PLA2R monoclonal antibodies have not been obtained. This lack hinders the measurement of chemical PLA2R antibody titers, which are critical for drug development.
Purpose: The purpose of this study is to obtain standard anti-human PLA2R monoclonal antibodies by creating a phage antibody library to screen for antibodies.
Materials and methods: Our study used CHO cells expressing the human PLA2R CysR-FnII-CTLD1 structural domain (CC1h) and obtained candidate antibodies by screening a human phage display library. These candidate antibodies were expressed in CHO cells, and their binding affinity for CC1h was determined by enzyme-linked immunosorbent assay (ELISA) and biological layer interferometry (BLI). In addition, we calibrated the representative antibody names of A13 and A13SP to obtain transforming factors using a commercial PLA2R antibody ELISA kit.
Results: 43 high-affinity candidate antibodies were obtained by screening human phage display libraries, and 9 groups of IgG antibodies and their IgG4SP subtype antibodies showed high affinity by CHO cell expression, ELISA, and BLI experiments, and we screened 1 group of antibodies with high protein expression levels and high affinity names of A13 and A13SP subtypes from these 9 antibodies. A few of the remaining 8 groups of antibodies and subtypes also showed high protein expression levels and high affinity, and these antibodies can also be used as alternative antibodies. In addition, we calibrated the representative antibody A13 using a commercial PLA2R antibody ELISA kit and obtained an average conversion factor of 1 RU = 70 ng, and we found that the standard curves of the A13 and A13SP subtype antibody groups exhibited a high concordance with that of the commercial PLA2R antibody ELISA kit, which was higher than that of the other alternative antibodies, and therefore this also indicates that the A13 and A13SP subtype antibodies are the most preferred antibody groups in our antibody library.
Conclusion: The A13 and A13SP subtype antibodies showed high protein expression levels and high antibody affinity, and the standard curves showed high concordance with the commercial kits, and this conclusion suggests that the A13 and A13SP subtype antibodies can be used as standard antibodies in the ELISA kits for the quantitative detection of human PLA2R antibodies.

*These authors contributed equally to this work and share first authorship.Correspondence to:
Guisen Li, MD
Department of Nephrology
Sichuan Provincial People’s Hospital
University of Electronic Science and Technology of China
Chengdu, China
or
Bing Lai, PhD
Department of Biological Products
Institute of Drug Development
Chengdu Di’ao Pharmaceutical Group Co., Ltd.
Chengdu, China
Email: [email protected]; [email protected]

Review

The MRGPRX2 paradigm shift: Redefining mast cell activation pathways in chronic urticaria

Kun Wu and Junlin Liu

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Volume 10 (2026) p. 52 - 62

Case  Report

Fondaparinux to treat cerebral venous sinus thrombosis complicated by heparin-induced thrombocytopenia during puerperium: A case report and literature review 

Meng Qi, Xuebing Feng, Lidan Jiang, Caikun Wu, Xiaoxia Zhang, Ping Guo, Ning Wang, and Yueqiao Xu

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Volume 64 (2026) p. 448 - 454

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 64 – No. 8/2026 (448-454)

Fondaparinux to treat cerebral venous sinus thrombosis complicated by heparin-induced thrombocytopenia during puerperium: A case report and literature review 

Meng Qi¹#²#³, Xuebing Feng¹#²#³, Lidan Jiang¹#²#³, Caikun Wu⁴, Xiaoxia Zhang⁵, Ping Guo⁶, Ning Wang¹#²#³, and Yueqiao Xu¹#²#³

¹Critical Care Unit, Department of Neurosurgery, Capital Medical University Xuanwu Hospital, ²National Center for Neurological Disorders, ³China International Neuroscience Institute, Beijing, ⁴Department of Neurosurgery, Xingguo People’s Hospital, Xingguo Hospital Affiliated to Gannan Medical University, Ganzhou, Jiangxi, ⁵Department of Critical Care Medicine, Wuhan Fourth Hospital, Puai Hospital Affiliated to Jianghan University, Wuhan, Hubei, and ⁶Stroke Ward, Xuchang Central Hospital Affiliated to Henan University of Science and Technology, Xuchang, Henan, China
Background: Cerebral venous sinus thrombosis (CVST) occurring during the puerperium is a rare yet life-threatening condition. The management of CVST becomes more complex when complicated by heparin-induced thrombocytopenia (HIT), a prothrombotic adverse effect of heparin therapy.
Case presentation: A case of puerperium-associated CVST with HIT is presented, in which fondaparinux was utilized as an alternative anticoagulant during the acute phase, followed by rivaroxaban. A multidisciplinary approach was employed, which included hematoma drainage, decompressive craniectomy, and endovascular recanalization. The patient achieved a favorable outcome, with a modified Rankin scale score of 2 at the 3-month follow-up.
Conclusion: This case highlights the potential safety and efficacy of fondaparinux in the management of CVST with HIT, emphasizing the critical role of a multidisciplinary approach in optimizing patient recovery.Correspondence to:
Yueqiao Xu, MD, PhD
Critical Care Unit, Department of Neurosurgery
Capital Medical University Xuanwu Hospital
45 Changchun Street, Xicheng District,
Beijing 100053, China
Email: [email protected]

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