Conformation-dependent anti-Aβ monoclonal antibody signatures of disease status and severity in urine of women with preeclampsia.
Conformation-dependent anti-Aβ monoclonal antibody signatures of disease status and severity in urine of women with preeclampsia.
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DOI：
10.1016/j.preghy.2022.01.007
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发表时间：
2022-06
影响因子：
2.2
通讯作者：
Buhimschi, Irina A.
中科院分区：
文献类型：
--
作者：
Valtanen, Rosa S.;Buhimschi, Catalin S.;Bahtiyar, Mert O.;Zhao, Guomao;Jing, Hongwu;Ackerman, William E.;Glabe, Charles G.;Buhimschi, Irina A.
先前的研究已经表明，患有先兆子痫（PE）的女性的尿液含有淀粉样蛋白样聚集体，其是亲脂性的（表现出对淀粉样蛋白染料刚果红的亲和力）并且与A11免疫反应，A11是针对前原纤维β-淀粉样蛋白寡聚体的多克隆血清，从而支持PE与蛋白质构象障碍（例如阿尔茨海默病和朊病毒病）之间的致病相似性。本研究的目的是使用具有先前表征的A11样表位的单克隆抗体询问PE尿液。筛选了超过100个构象依赖性单克隆抗体，并选择了3个（mA11 - 09、mA11 - 89和mA11 - 205）在196个尿液样本中进行进一步确认，分组如下：严重特征PE（sPE，n = 114）、无严重特征的PE（mPE，n = 30）、慢性高血压（crHTN，n = 14）和血压正常的妊娠对照（P-CRL，n = 38）。我们发现，所选的构象特异性单克隆抗体在不同严重程度的PE患者与P-CRL和crHTN患者之间进行了区分。通过使用潜在类别分析（LCA），我们确定了三类受试者：第1类（n = 94）包括尿液嗜酸性和单克隆抗体反应性的患者。这些女性更可能被诊断为早发性sPE，并有严重的高血压和蛋白尿; 2类患者（n = 55）的嗜中性粒细胞和抗体阴性。这些主要是P-CRL和crHTN患者。最后，第3类患者（n = 48）尿嗜中性粒细胞阳性，尽管强度较低，但单克隆免疫反应性阴性。这些女性主要被诊断为mPE或迟发性sPE。总的来说，我们的研究验证了PE尿液的构象依赖性A β免疫反应性，其与尿液嗜中性粒细胞增多症一起可能代表疾病严重程度的额外指标。
Prior research has shown that urine of women with preeclampsia (PE) contains amyloid-like aggregates that are congophilic (exhibit affinity for the amyloidophilic dye Congo red) and immunoreactive with A11, a polyclonal serum against prefibrillar β-amyloid oligomers, thereby supporting pathogenic similarity between PE and protein conformational disorders such as Alzheimer’s and prion disease. The objective of this study was to interrogate PE urine using monoclonal antibodies with previously characterized A11-like epitopes. Over 100 conformation-dependent monoclonals were screened and three (mA11–09, mA11–89, and mA11–205) selected for further confirmation in 196 urine samples grouped as follows: severe features PE (sPE, n=114), PE without severe features (mPE, n=30), chronic hypertension (crHTN, n=14) and normotensive pregnant control (P-CRL, n=38). We showed that the selected conformation-specific monoclonals distinguished among patients with varying severities of PE from P-CRL and patients with crHTN. By use of latent class analysis (LCA) we identified three classes of subjects: Class 1 (n=94) comprised patients whose urine was both congophilic and reactive with the monoclonals. These women were more likely diagnosed with early-onset sPE and had severe hypertension and proteinuria; Class 2 patients (n=55) were negative for congophilia and against the antibodies. These were predominantly P-CRL and crHTN patients. Lastly, Class 3 patients (n=48) were positive for urine congophilia, albeit at lower intensity, but negative for monoclonal immunoreactivities. These women were diagnosed primarily as mPE or late-onset sPE. Collectively, our study validates conformation-dependent Aβ imunoreactivity of PE urine which in conjunction to urine congophilia may represent an additional indicator of disease severity.
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影响因子：
15.1
作者：
Kayed R;Canto I;Breydo L;Rasool S;Lukacsovich T;Wu J;Albay R 3rd;Pensalfini A;Yeung S;Head E;Marsh JL;Glabe C
通讯作者：
Glabe C
DOI：
10.1016/j.bbagen.2012.08.016
发表时间：
2012-12-01
影响因子：
3
作者：
Arai, Hiromi;Glabe, Charles;Luecke, Hartmut
通讯作者：
Luecke, Hartmut
影响因子：
3.1
作者：
Allanson, Emma R.;Muller, Mari;Pattinson, Robert C.
通讯作者：
Pattinson, Robert C.
影响因子：
7.2
作者：
通讯作者：
--
DOI：
10.1073/pnas.95.11.6448
发表时间：
1998-05-26
影响因子：
11.1
作者：
Lambert, MP;Barlow, AK;Klein, WL
通讯作者：
Klein, WL