Autoantibodies to Perilipin-1 define a subset of acquired generalized lipodystrophy
Year: 2022
Type: other
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 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.
Authors: 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, Abhinmanyu Garg, Joseph L. DeRisi
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4282980799