Increasing the accuracy of proteomic typing by decellularisation of amyloid tissue biopsies
Increasing the accuracy of proteomic typing by decellularisation of amyloid tissue biopsies
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DOI：
10.1016/j.jprot.2017.06.016
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发表时间：
2017-08-08
影响因子：
3.3
通讯作者：
Bellotti, Vittorio
中科院分区：
文献类型：
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作者：
Mangione, P. Patrizia;Mazza, Giuseppe;Bellotti, Vittorio
系统性淀粉样变性的诊断和治疗取决于对形成组织沉积物的特定淀粉样原纤维蛋白的准确鉴定。确认单克隆免疫球蛋白轻链淀粉样变性 (AL)，需要细胞毒性化疗，并避免在非 AL 淀粉样变性中进行此类治疗，这一点尤为重要。蛋白质组分析直接表征淀粉样蛋白。它补充了淀粉样蛋白的免疫组织化学染色以鉴定原纤维蛋白和基因测序以鉴定原纤维前体中的突变。然而，蛋白质组学有时会检测到不止一种潜在的淀粉样蛋白，尤其是免疫球蛋白和运甲状腺素蛋白，它们是丰富的血浆蛋白。模糊的结果在老年人中最具挑战性，因为该群体通常同时存在 AL 和运甲状腺素蛋白 (ATTR) 淀粉样变性。我们最近描述了一种组织脱细胞程序，该程序保留了淀粉样蛋白的结构、完整性和组成，但去除了未整合到沉积物中的蛋白质。在这里，我们表明在蛋白质组分析之前使用此程序可以消除歧义并提高诊断准确性。意义：明确鉴定引起淀粉样变性疾病的蛋白质对于正确诊断和治疗至关重要。作为原理证明，我们从患有不同类型淀粉样变性的患者中选择了一些心脏和脂肪组织活检，结果表明经典的去细胞化程序增强了罪魁祸首蛋白识别的特异性，减少了模糊性和误诊的风险。 (C) 2017 年作者。由 Elsevier B.V. 出版
Diagnosis and treatment of systemic amyloidosis depend on accurate identification of the specific amyloid fibril protein forming the tissue deposits. Confirmation of monoclonal immunoglobulin light chain amyloidosis (AL), requiring cytotoxic chemotherapy, and avoidance of such treatment in non-AL amyloidosis, are particularly important. Proteomic analysis characterises amyloid proteins directly. It complements immunohistochemical staining of amyloid to identify fibril proteins and gene sequencing to identify mutations in the fibril precursors. However, proteomics sometimes detects more than one potentially amyloidogenic protein, especially immunoglobulins and transthyretin which are abundant plasma proteins. Ambiguous results are most challenging in the elderly as both AL and transthyretin (ATTR) amyloidosis are usually present in this group. We have lately described a procedure for tissue decellularisation which retains the structure, integrity and composition of amyloid but removes proteins that are not integrated within the deposits. Here we show that use of this procedure before proteomic analysis eliminates ambiguity and improves diagnostic accuracy. Significance: Unequivocal identification of the protein causing amyloidosis disease is crucial for correct diagnosis and treatment. As a proof of principle, we selected a number of cardiac and fat tissue biopsies from patients with various types of amyloidosis and show that a classical procedure of decellularisation enhances the specificity of the identification of the culprit protein reducing ambiguity and the risk of misdiagnosis. (C) 2017 The Authors. Published by Elsevier B.V.