Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as autoantibodies are generally lacking. Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte-specific lipid droplet protein Perilipin-1 (PLIN1) in a murine model of Autoimmune Polyendocrine Syndrome 1 (APS1). We then tested for PLIN1 autoantibodies in human subjects with acquired lipodystrophy with two independent severe breaks in immune tolerance (including APS1) along with controls using a specific Radioligand Binding Assay and indirect immunofluorescence on fat tissue. We identified autoantibodies to PLIN1 in these two cases, including the first reported case of APS1 with acquired lipodystrophy and a second patient who acquired lipodystrophy as an immune-related adverse event following cancer immunotherapy. Lastly, we also found PLIN1 autoantibodies to be specifically enriched in a subset of patients with acquired generalized lipodystrophy (17/46; 37%) particularly those with panniculitis and other features of autoimmunity. These data lend additional support to new literature that suggests that PLIN1 autoantibodies represent a marker of acquired autoimmune lipodystrophies and further link them to a break in immune tolerance.

中文翻译：

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Perilipin-1 的自身抗体定义了获得性全身性脂肪代谢障碍的一个子集

获得性脂肪营养不良通常被表征为脂肪营养不良的特发性亚型。尽管怀疑是免疫介导的病理学，但通常缺乏诸如自身抗体之类的生物标志物。在这里，我们使用无偏见的蛋白质组范围筛选方法来鉴定自身免疫性多内分泌综合征 1 (APS1) 小鼠模型中针对脂肪细胞特异性脂滴蛋白 Perilipin-1 (PLIN1) 的自身抗体。然后，我们在患有获得性脂肪营养不良的人类受试者中测试了 PLIN1 自身抗体，免疫耐受性有两个独立的严重中断（包括 APS1）以及使用特定放射性配体结合试验和脂肪组织间接免疫荧光的对照。我们在这两种情况下鉴定了 PLIN1 的自身抗体，包括第一例报告的 APS1 患有获得性脂肪营养不良的病例和第二例获得性脂肪营养不良作为癌症免疫治疗后免疫相关不良事件的患者。最后，我们还发现 PLIN1 自身抗体在获得性全身性脂肪营养不良患者（17/46；37%）中特别富集，特别是那些患有脂膜炎和其他自身免疫特征的患者。这些数据为新文献提供了额外的支持，这些文献表明 PLIN1 自身抗体代表获得性自身免疫性脂肪营养不良的标志物，并进一步将它们与免疫耐受的中断联系起来。37%）尤其是那些患有脂膜炎和其他自身免疫特征的人。这些数据为新文献提供了额外的支持，这些文献表明 PLIN1 自身抗体代表获得性自身免疫性脂肪营养不良的标志物，并进一步将它们与免疫耐受的中断联系起来。37%）尤其是那些患有脂膜炎和其他自身免疫特征的人。这些数据为新文献提供了额外的支持，这些文献表明 PLIN1 自身抗体代表获得性自身免疫性脂肪营养不良的标志物，并进一步将它们与免疫耐受的中断联系起来。