Abstract：
Systemic amyloid light-chain (AL) amyloidosis is an infrequent disease in which amyloid fibrils derived from the immunoglobulin light chain are deposited in systemic organs, resulting in functional impairment. This disease has been notably uncommon in animals, and nonhuman primates have not been reported to develop it. In this study, we identified the systemic AL kappa chain amyloidosis in a captive Bornean orangutan (Pongo pygmaeus) and analyzed its pathogenesis. Amyloid deposits were found severely in the submucosa of the large intestine, lung, mandibular lymph nodes, and mediastinal lymph nodes, with milder lesions in the liver and kidney. Mass spectrometry-based proteomic analysis revealed an abundant constant domain of the immunoglobulin kappa chain in the amyloid deposits. Immunohistochemistry further confirmed that the amyloid deposits were positive for immunoglobulin kappa chains. In this animal, AL amyloidosis resulted in severe involvement of the gastrointestinal submucosa and lymph nodes, which is consistent with the characteristics of AL amyloidosis in humans, suggesting that AL amyloid may have a similar deposition mechanism across species. This report enhances the pathological understanding of systemic AL amyloidosis in animals by providing a detailed characterization of this disease based on proteomic analysis.
摘要：
系统性淀粉样蛋白轻链（AL）淀粉样变性是一种罕见的疾病，其中源自免疫球蛋白轻链的淀粉样原纤维沉积在全身器官中，导致功能损害。这种疾病在动物中非常罕见，和非人类灵长类动物没有报道发展它。在这项研究中,我们在圈养的婆罗洲猩猩（Pongopygmaeus）中鉴定了系统性ALκ链淀粉样变性，并分析了其发病机制。在大肠粘膜下层发现了严重的淀粉样沉积物，肺，下颌淋巴结，纵隔淋巴结,肝脏和肾脏的病变较轻。基于质谱的蛋白质组分析揭示了淀粉样蛋白沉积物中免疫球蛋白κ链的丰富恒定结构域。免疫组织化学进一步证实淀粉样蛋白沉积物对免疫球蛋白κ链呈阳性。在这种动物中，AL淀粉样变性导致胃肠道粘膜下层和淋巴结严重受累，这与人类AL淀粉样变性的特征一致，这表明AL淀粉样蛋白可能在不同物种之间具有相似的沉积机制。该报告通过基于蛋白质组学分析提供该疾病的详细表征，增强了对动物系统性AL淀粉样变性的病理学理解。
