학술논문
Autoantibodies to Perilipin-1 Define a Subset of Acquired Generalized Lipodystrophy.
Document Type
article
Author
Mandel-Brehm, Caleigh; Vazquez, Sara E; Liverman, Christopher; Cheng, Mickie; Quandt, Zoe; Kung, Andrew F; Parent, Audrey; Miao, Brenda; Disse, Emmanuel; Cugnet-Anceau, Christine; Dalle, Stéphane; Orlova, Elizaveta; Frolova, Elena; Alba, Diana; Michels, Aaron; Oftedal, Bergithe E; Lionakis, Michail S; Husebye, Eystein S; Agarwal, Anil K; Li, Xilong; Zhu, Chengsong; Li, Quan; Oral, Elif; Brown, Rebecca; Anderson, Mark S; Garg, Abhimanyu; DeRisi, Joseph L
Source
Diabetes. 72(1)
Subject
Language
Abstract
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 type 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 control subjects 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 of 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.