Liling Wu, Zhihang Su, Bo Tang, Yuna Chen, Haofei Hu, Yuan Cheng, Jianyu Chen, Qijun Wan
{"title":"PLA2R1表位扩散的膜性肾病不良预后:一项前瞻性研究。","authors":"Liling Wu, Zhihang Su, Bo Tang, Yuna Chen, Haofei Hu, Yuan Cheng, Jianyu Chen, Qijun Wan","doi":"10.1159/000545133","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In primary membranous nephropathy (MN), 80% of patients harbor antibodies against phospholipase A2 receptor 1 (PLA2R1), closely linked to disease prognosis. Prior research has validated the correlation between antibodies directed towards the cysteine-rich(CysR) and C-type lectin 1, 7, and 8(CTLD1, CTLD7, and CTLD8) domains of PLA2R1 and outcomes in MN.</p><p><strong>Methods: </strong>In a prospective cohort of 52 patients with newly diagnosed PLA2R1-MN, with urine protein ≥ 3.5 g/24 hours and estimated glomerular filtration rate ≥30 mL/min/1.73 m², we studied epitope-spreading patterns and domain-specific PLA2R1-Ab clinically using western blot and ELISA. The primary outcome was a combination of remission at 12 months. Kaplan-Meier curves and Multivariable Cox regression were employed to compare the single and multiple epitope patients.</p><p><strong>Results: </strong>All patients had anti-CysR antibodies. 26(50.0%) exhibited multi-domain recognition, with one patient specifically recognizing the CTLD8 domain. A significant association was observed between PLA2R1-Ab and CysR-Ab(r = 0.869, P <0.001), as well as with anti-CTLD1 antibody(r = 0.803, P <0.001). During a median follow-up of 11 months(IQR, 6.0-17.0), 27 patients(65.9%) experienced complete or partial nephrotic syndrome remission. Notably, the multi-domain recognition exhibited a reduced remission rate compared to the single-domain(44.44% vs 82.61%, P = 0.011, alongside higher concentrations of anti-PLA2R1 antibodies. A higher baseline level of anti-CTLD1 was notably linked to a lower likelihood of remission. In a univariate analysis, multi-domain recognition decreases the probability of remission[HR, 0.38 (95% CI, 0.16-0.87), P = 0.022]. After the Kaplan-Meier analysis, the multi-domain group showed lower remission rates than the single-domain group at various time points.</p><p><strong>Conclusion: </strong>The PLA2R1 epitope spreading is a potent tool for monitoring disease severity and stratifying patients based on renal outcomes for prognostic purposes. Hence, we advocate evaluating epitope spreading at the baseline stage when determining early therapeutic interventions for individuals diagnosed with MN.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-20"},"PeriodicalIF":4.3000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Adverse Prognosis in Membranous Nephropathy with PLA2R1 Epitope Spreading: A Prospective Study.\",\"authors\":\"Liling Wu, Zhihang Su, Bo Tang, Yuna Chen, Haofei Hu, Yuan Cheng, Jianyu Chen, Qijun Wan\",\"doi\":\"10.1159/000545133\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In primary membranous nephropathy (MN), 80% of patients harbor antibodies against phospholipase A2 receptor 1 (PLA2R1), closely linked to disease prognosis. Prior research has validated the correlation between antibodies directed towards the cysteine-rich(CysR) and C-type lectin 1, 7, and 8(CTLD1, CTLD7, and CTLD8) domains of PLA2R1 and outcomes in MN.</p><p><strong>Methods: </strong>In a prospective cohort of 52 patients with newly diagnosed PLA2R1-MN, with urine protein ≥ 3.5 g/24 hours and estimated glomerular filtration rate ≥30 mL/min/1.73 m², we studied epitope-spreading patterns and domain-specific PLA2R1-Ab clinically using western blot and ELISA. The primary outcome was a combination of remission at 12 months. Kaplan-Meier curves and Multivariable Cox regression were employed to compare the single and multiple epitope patients.</p><p><strong>Results: </strong>All patients had anti-CysR antibodies. 26(50.0%) exhibited multi-domain recognition, with one patient specifically recognizing the CTLD8 domain. A significant association was observed between PLA2R1-Ab and CysR-Ab(r = 0.869, P <0.001), as well as with anti-CTLD1 antibody(r = 0.803, P <0.001). During a median follow-up of 11 months(IQR, 6.0-17.0), 27 patients(65.9%) experienced complete or partial nephrotic syndrome remission. Notably, the multi-domain recognition exhibited a reduced remission rate compared to the single-domain(44.44% vs 82.61%, P = 0.011, alongside higher concentrations of anti-PLA2R1 antibodies. A higher baseline level of anti-CTLD1 was notably linked to a lower likelihood of remission. In a univariate analysis, multi-domain recognition decreases the probability of remission[HR, 0.38 (95% CI, 0.16-0.87), P = 0.022]. After the Kaplan-Meier analysis, the multi-domain group showed lower remission rates than the single-domain group at various time points.</p><p><strong>Conclusion: </strong>The PLA2R1 epitope spreading is a potent tool for monitoring disease severity and stratifying patients based on renal outcomes for prognostic purposes. Hence, we advocate evaluating epitope spreading at the baseline stage when determining early therapeutic interventions for individuals diagnosed with MN.</p>\",\"PeriodicalId\":7570,\"journal\":{\"name\":\"American Journal of Nephrology\",\"volume\":\" \",\"pages\":\"1-20\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-03-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Nephrology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000545133\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000545133","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:在原发性膜性肾病(MN)中,80%的患者携带针对磷脂酶A2受体1 (PLA2R1)的抗体,该抗体与疾病预后密切相关。先前的研究已经证实了针对PLA2R1富含半胱氨酸(CysR)和c型凝集素1,7和8(CTLD1, CTLD7和CTLD8)结构域的抗体与MN预后之间的相关性。方法:在52例新诊断的PLA2R1-MN患者中,尿蛋白≥3.5 g/24小时,肾小球滤过率≥30 mL/min/1.73 m²,我们使用western blot和ELISA技术研究PLA2R1-Ab的表位扩散模式和结构域特异性。主要结果是12个月时的缓解组合。采用Kaplan-Meier曲线和多变量Cox回归对单表位患者和多表位患者进行比较。结果:所有患者均有抗cysr抗体。26例(50.0%)表现出多域识别,1例患者特异性识别CTLD8域。PLA2R1-Ab与CysR-Ab呈显著相关性(r = 0.869, P <0.001),与抗ctld1抗体呈显著相关性(r = 0.803, P <0.001)。在中位随访11个月(IQR, 6.0-17.0)期间,27例患者(65.9%)完全或部分缓解肾病综合征。值得注意的是,与单结构域相比,多结构域识别表现出更低的缓解率(44.44% vs 82.61%, P = 0.011),同时抗pla2r1抗体浓度更高。较高的抗ctld1基线水平与较低的缓解可能性明显相关。在单变量分析中,多域识别降低了缓解的概率[HR, 0.38 (95% CI, 0.16-0.87), P = 0.022]。Kaplan-Meier分析显示,在不同时间点,多区域组的缓解率低于单区域组。结论:PLA2R1表位扩散是监测疾病严重程度和基于肾脏预后对患者进行分层的有效工具。因此,我们主张在基线阶段评估表位扩散,以确定诊断为MN的个体的早期治疗干预措施。
Adverse Prognosis in Membranous Nephropathy with PLA2R1 Epitope Spreading: A Prospective Study.
Background: In primary membranous nephropathy (MN), 80% of patients harbor antibodies against phospholipase A2 receptor 1 (PLA2R1), closely linked to disease prognosis. Prior research has validated the correlation between antibodies directed towards the cysteine-rich(CysR) and C-type lectin 1, 7, and 8(CTLD1, CTLD7, and CTLD8) domains of PLA2R1 and outcomes in MN.
Methods: In a prospective cohort of 52 patients with newly diagnosed PLA2R1-MN, with urine protein ≥ 3.5 g/24 hours and estimated glomerular filtration rate ≥30 mL/min/1.73 m², we studied epitope-spreading patterns and domain-specific PLA2R1-Ab clinically using western blot and ELISA. The primary outcome was a combination of remission at 12 months. Kaplan-Meier curves and Multivariable Cox regression were employed to compare the single and multiple epitope patients.
Results: All patients had anti-CysR antibodies. 26(50.0%) exhibited multi-domain recognition, with one patient specifically recognizing the CTLD8 domain. A significant association was observed between PLA2R1-Ab and CysR-Ab(r = 0.869, P <0.001), as well as with anti-CTLD1 antibody(r = 0.803, P <0.001). During a median follow-up of 11 months(IQR, 6.0-17.0), 27 patients(65.9%) experienced complete or partial nephrotic syndrome remission. Notably, the multi-domain recognition exhibited a reduced remission rate compared to the single-domain(44.44% vs 82.61%, P = 0.011, alongside higher concentrations of anti-PLA2R1 antibodies. A higher baseline level of anti-CTLD1 was notably linked to a lower likelihood of remission. In a univariate analysis, multi-domain recognition decreases the probability of remission[HR, 0.38 (95% CI, 0.16-0.87), P = 0.022]. After the Kaplan-Meier analysis, the multi-domain group showed lower remission rates than the single-domain group at various time points.
Conclusion: The PLA2R1 epitope spreading is a potent tool for monitoring disease severity and stratifying patients based on renal outcomes for prognostic purposes. Hence, we advocate evaluating epitope spreading at the baseline stage when determining early therapeutic interventions for individuals diagnosed with MN.
期刊介绍:
The ''American Journal of Nephrology'' is a peer-reviewed journal that focuses on timely topics in both basic science and clinical research. Papers are divided into several sections, including: