Discrimination of MSA-P and MSA-C by RT-QuIC analysis of olfactory mucosa: the first assessment of assay reproducibility between two specialized laboratories.
Discrimination of MSA-P and MSA-C by RT-QuIC analysis of olfactory mucosa: the first assessment of assay reproducibility between two specialized laboratories.
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DOI：
10.1186/s13024-021-00491-y
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发表时间：
2021-12-11
影响因子：
15.1
通讯作者：
Moda F
中科院分区：
文献类型：
--
作者：
Bargar C;De Luca CMG;Devigili G;Elia AE;Cilia R;Portaleone SM;Wang W;Tramacere I;Bistaffa E;Cazzaniga FA;Felisati G;Legname G;Di Fonzo A;Xu R;Gunzler SA;Giaccone G;Eleopra R;Chen SG;Moda F
检测脑中病理和疾病相关的α-突触核蛋白（αSynD）是制定多系统萎缩（MSA）和帕金森病（PD）的明确诊断所必需的。我们最近发现αSynD可以在MSA和PD患者的嗅粘膜（OM）中检测到。因此，我们对从帕金森病（MSA-P）和小脑（MSA-C）表型的PD和MSA患者中采集的OM样本进行了基于α-突触核蛋白实时震颤诱导转换（αSyn_RT-QuIC）分析的首次实验室间研究。从可能诊断为MSA-P（n = 20，平均病程4.4年）、MSA-C（n = 10，平均病程4年）、PD（n = 13，平均病程8年）和健康对照受试者（HS）（n = 11）的患者中前瞻性采集OM样本。在两个独立的专业实验室（一个位于意大利（ITA-lab），另一个位于美国（USA-lab）），采用αSyn_RT-QuIC分析每份样本。两个实验室均已开发并使用了协调的αSyn_RT-QuIC分析方法。结果与人口统计学和临床数据相关。实验室间αSyn_RT-QuIC分析结果的评价者间一致性（IAR）为96%（Kappa = 0.93，95% CI 0.83-1.00）。特别是，在9/13例PD患者（灵敏度69%，IAR 100%）和18/20例MSA-P患者（灵敏度90%，IAR 100%）的OM中发现了αSyn_RT-QuIC接种活性。有趣的是，从MSA-C患者中采集的样本未诱导αSyn_RT-QuIC接种活性，但USA-lab中的1例受试者除外。因此，我们发现MSA-P和MSA-C诱导相反的效应。无论疾病诊断如何，αSyn_RT-QuIC接种活性与一些临床参数相关，包括僵硬和姿势不稳定。我们的研究提供了证据，OM-αSynD可能作为一种新的生物标志物，用于PD、MSA-P和MSA-C的准确临床诊断。此外，αSyn_RT-QuIC代表了一种可靠的检测方法，可以区分MSA-P患者和MSA-C患者，并可能导致患者分层和新兴药物治疗和临床试验选择的显著进步。在线版本包含补充材料，可通过10.1186/s13024-021-00491-y获取。
Detection of the pathological and disease-associated alpha-synuclein (αSynD) in the brain is required to formulate the definitive diagnosis of multiple system atrophy (MSA) and Parkinson’s disease (PD). We recently showed that αSynD can be detected in the olfactory mucosa (OM) of MSA and PD patients. For this reason, we have performed the first interlaboratory study based on α-synuclein Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC) analysis of OM samples collected from PD and MSA patients with the parkinsonian (MSA-P) and cerebellar (MSA-C) phenotypes. OM samples were prospectively collected from patients with a probable diagnosis of MSA-P (n = 20, mean disease duration 4.4 years), MSA-C (n = 10, mean disease duration 4 years), PD (n = 13, mean disease duration 8 years), and healthy control subjects (HS) (n = 11). Each sample was analyzed by αSyn_RT-QuIC in two independent specialized laboratories, one located in Italy (ITA-lab) and one located in the USA (USA-lab). Both laboratories have developed and used harmonized αSyn_RT-QuIC analytical procedures. Results were correlated with demographic and clinical data. The αSyn_RT-QuIC analysis reached a 96% interrater agreement of results (IAR) between laboratories (Kappa = 0.93, 95% CI 0.83–1.00). In particular, αSyn_RT-QuIC seeding activity was found in the OM of 9/13 patients with PD (sensitivity 69%, IAR 100%) and 18/20 patients with MSA-P (sensitivity 90%, IAR 100%). Interestingly, samples collected from patients with MSA-C did not induce αSyn_RT-QuIC seeding activity, except for one subject in USA-lab. Therefore, we found that MSA-P and MSA-C induced opposite effects. Regardless of disease diagnosis, the αSyn_RT-QuIC seeding activity correlated with some clinical parameters, including the rigidity and postural instability. Our study provides evidence that OM-αSynD may serve as a novel biomarker for accurate clinical diagnoses of PD, MSA-P, and MSA-C. Moreover, αSyn_RT-QuIC represents a reliable assay that can distinguish patients with MSA-P from those with MSA-C, and may lead to significant advancements in patients stratification and selection for emerging pharmacological treatments and clinical trials. The online version contains supplementary material available at 10.1186/s13024-021-00491-y.
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影响因子：
8.6
作者：
Kang, Un Jung;Boehme, Amelia K.;Soto, Claudio
通讯作者：
Soto, Claudio
影响因子：
7.1
作者：
Groveman BR;Orrù CD;Hughson AG;Raymond LD;Zanusso G;Ghetti B;Campbell KJ;Safar J;Galasko D;Caughey B
通讯作者：
Caughey B
DOI：
10.1002/mds.28242
发表时间：
2020-12
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Manne S;Kondru N;Jin H;Serrano GE;Anantharam V;Kanthasamy A;Adler CH;Beach TG;Kanthasamy AG
通讯作者：
Kanthasamy AG
影响因子：
6.2
作者：
Manne, Sireesha;Kondru, Naveen;Kanthasamy, Anumantha G.
通讯作者：
Kanthasamy, Anumantha G.
影响因子：
14.5
作者：
Miki, Yasuo;Foti, Sandrine C.;Holton, Janice L.
通讯作者：
Holton, Janice L.