Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona.
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F Hoffman-La Roche, Ltd, Basel, Switzerland.
J Neuropathol Exp Neurol. 2018 Sep 1;77(9):793-802. doi: 10.1093/jnen/nly056.
Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images.
外周组织活检免疫组化（IHC）α-突触核蛋白（Asyn）病理学可能是帕金森病（PD）的生物标志物。多中心系统性突触核蛋白采样研究（S4）正在评估来自 60 名 PD 和 20 名对照受试者的皮肤、结肠和颌下腺活检组织中的 IHC Asyn 病理学。Asyn 病理学由一组经过专门培训的神经病理学家进行盲法评估。初步工作评估了 2 种候选免疫过氧化物酶方法，使用了来自 3 种组织福尔马林固定、石蜡包埋块的 PD 和对照尸检衍生切片集。这两种方法的特异性均为 100%；一种使用 5C12 单克隆抗体，在皮肤中更敏感（67%比 33%），因此被选择用于 S4 的进一步使用。4 名受训神经病理学家接受了 S4 组织病理学阅读培训；在随后的测试中，他们的评分与培训神经病理学家在玻璃载玻片和数字图像上的评分进行了比较。除了皮肤外，所有读者在所有组织类型的玻璃载玻片和数字图像上的特异性和敏感性均接近 100%，在皮肤中，数字图像的敏感性平均为 75%，玻璃载玻片的敏感性为 83.5%。受训者和培训师之间的半定量（0-3）密度评分平均一致性为玻璃载玻片上的 67%，数字图像上的 62%。
