A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients.
A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients.
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DOI：
10.1016/j.ekir.2020.07.028
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发表时间：
2020-10
影响因子：
6
通讯作者：
Cravedi P
中科院分区：
文献类型：
--
作者：
Cantarelli C;Jarque M;Angeletti A;Manrique J;Hartzell S;O'Donnell T;Merritt E;Laserson U;Perin L;Donadei C;Anderson L;Fischman C;Chan E;Draibe J;Fulladosa X;Torras J;Riella LV;La Manna G;Fiaccadori E;Maggiore U;Bestard O;Cravedi P
原发性膜性肾病（MN）以存在抗足细胞抗体为特征，但描述循环淋巴细胞表型和功能异常的研究有限。我们使用流式细胞术分析了30名MN患者（开始免疫抑制之前）与31名非免疫介导的慢性肾脏疾病（CKD）患者和12名健康个体的68种不同的B细胞和t细胞亚群。我们还测量了MN患者和健康对照者的19种血清细胞因子。最后，我们通过质母细胞（测量培养上清液中的抗体和新开发的FluoroSpot法[AutoImmun diagnostics， Strasberg，德国]）定量了磷脂酶A2受体（PLA2R）特异性IgG的体外产生，并通过噬菌体免疫沉淀测序（PhIP-Seq）评估了循环抗体库。经多次检测调整后，MN患者浆细胞和调节性B细胞（BREG）较对照组显著升高（P < 0.05）。循环浆细胞百分比与血清抗pla2r抗体水平相关（P = 0.042），并与疾病活动性相关。MN患者循环pla2r特异性记忆B细胞（mBCs）产生的体外扩增pla2r特异性IgG产质母细胞与血清抗pla2r IgG抗体相关（P < 0.001）。肿瘤坏死因子-α (TNF-α)是MN患者中唯一显著升高的细胞因子（P < 0.05），而自身抗体和抗病毒抗体库在各研究组之间无显著差异。这种广泛的表型和功能免疫表征表明，自身反应性浆细胞存在于MN患者的循环中，提供了新的治疗靶点和疾病活性的候选生物标志物。
Primary membranous nephropathy (MN) is characterized by the presence of antipodocyte antibodies, but studies describing phenotypic and functional abnormalities in circulating lymphocytes are limited. We analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN patients (before initiating immunosuppression) compared with 31 patients with non–immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We also measured 19 serum cytokines in MN patients and in healthy controls. Lastly, we quantified the ex vivo production of phospholipase A2 receptor (PLA2R)-specific IgG by plasmablasts (measuring antibodies in culture supernatants and by the newly developed FluoroSpot assay [AutoImmun Diagnostika, Strasberg, Germany]) and assessed the circulating antibody repertoire by phage immunoprecipitation sequencing (PhIP-Seq). After adjusting for multiple testing, plasma cells and regulatory B cells (BREG) were significantly higher (P < 0.05) in MN patients compared with both control groups. The percentages of circulating plasma cells correlated with serum anti-PLA2R antibody levels (P = 0.042) and were associated with disease activity. Ex vivo–expanded PLA2R-specific IgG-producing plasmablasts generated from circulating PLA2R-specific memory B cells (mBCs) correlated with serum anti-PLA2R IgG antibodies (P < 0.001) in MN patients. Tumor necrosis factor-α (TNF-α) was the only significantly increased cytokine in MN patients (P < 0.05), whereas there was no significant difference across study groups in the autoantibody and antiviral antibody repertoire. This extensive phenotypic and functional immune characterization shows that autoreactive plasma cells are present in the circulation of MN patients, providing a new therapeutic target and a candidate biomarker of disease activity.
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影响因子：
13.2
作者：
Glassock, Richard J.
通讯作者：
Glassock, Richard J.
影响因子：
5.4
作者：
Haas, J;Hug, A;Wildemann, B
通讯作者：
Wildemann, B
第7章：特发性膜肾病。
影响因子：
5.5
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1003224
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Long SA;Buckner JH
通讯作者：
Buckner JH
影响因子：
4.1
作者：
Lateb, Mael;Ouahmi, Hajar;Seitz-Polski, Barbara
通讯作者：
Seitz-Polski, Barbara