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Autoantibodies to Perilipin-1 define a subset of acquired generalized lipodystrophy

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posted on 16.06.2022, 16:51 authored by 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


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.


Z.Q. was supported by the American Diabetes Association grant 1- 19-PDF-131. JDR is funded by a grant from Chan Zuckerberg Biohub. JDR and CMB are funded by the National Institute of Mental Health (NIMH) of the NIH (award 1R01MH122471-01). CMB is funded by The Emiko Terasaki Foundation (Project 7027742 / Fund B73335) and by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (award 1K99NS117800-01). SEV is funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH (award 1F30DK123915-01). MSL is funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (ZIA AI001175). MA is funded by the National Institute of Allergy and Infectious Diseases (5P01AI118688),the Helmsley Charitable Trust, and the Chan Zuckerberg Biohub. EH is funded by Stiftelsen Kristian Gerhard Jebsen, The Novo Nordisk Foundation, The Research Council of Norway and the Regional Health Authorities of Western Norway. AKA and AG are funded by the National Institutes of Health grant, R01-DK105448 and the Southwestern Medical Foundation, RB is funded by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases.