Autoantibodies to Perilipin-1 Define a Subset of Acquired Generalized Lipodystrophy.
Caleigh Mandel-Brehm, Sara E Vazquez, Christopher Liverman, Mickie Cheng, Zoe Quandt, Andrew F Kung, Audrey Parent, Brenda Miao, Emmanuel Disse, Christine Cugnet-Anceau, Stéphane Dalle, Elizaveta Orlova, Elena Frolova, Diana Alba, Aaron Michels, Bergithe E Oftedal, Michail S Lionakis, Eystein S Husebye, Anil K Agarwal, Xilong Li, Chengsong Zhu, Quan Li, Elif Oral, Rebecca Brown, Mark S Anderson, Abhimanyu Garg, Joseph L DeRisi
Diabetes 2023 Jan 01Acquired 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. © 2022 by the American Diabetes Association.
Citation
Caleigh Mandel-Brehm, Sara E Vazquez, Christopher Liverman, Mickie Cheng, Zoe Quandt, Andrew F Kung, Audrey Parent, Brenda Miao, Emmanuel Disse, Christine Cugnet-Anceau, Stéphane Dalle, Elizaveta Orlova, Elena Frolova, Diana Alba, Aaron Michels, Bergithe E Oftedal, Michail S Lionakis, Eystein S Husebye, Anil K Agarwal, Xilong Li, Chengsong Zhu, Quan Li, Elif Oral, Rebecca Brown, Mark S Anderson, Abhimanyu Garg, Joseph L DeRisi. Autoantibodies to Perilipin-1 Define a Subset of Acquired Generalized Lipodystrophy. Diabetes. 2023 Jan 01;72(1):59-70
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PMID: 35709010
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