학술논문
Autoantibodies to Perilipin-1 Define a Subset of Acquired Generalized Lipodystrophy.
Document Type
Academic Journal
Author
Mandel-Brehm C; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA.; Vazquez SE; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA.; Diabetes Center, University of California, San Francisco, San Francisco, CA.; Liverman C; Department of Pathology, University of California, San Francisco, San Francisco, CA.; Cheng M; Diabetes Center, University of California, San Francisco, San Francisco, CA.; Quandt Z; Diabetes Center, University of California, San Francisco, San Francisco, CA.; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Kung AF; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA.; Parent A; Diabetes Center, University of California, San Francisco, San Francisco, CA.; Miao B; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA.; Diabetes Center, University of California, San Francisco, San Francisco, CA.; Disse E; Endocrinology Diabetology and Nutrition Department, Lyon Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.; ImmuCare, Cancer Institute of Hospices Civils de Lyon (IC-HCL), Lyon, France.; Cugnet-Anceau C; Endocrinology Diabetology and Nutrition Department, Lyon Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.; ImmuCare, Cancer Institute of Hospices Civils de Lyon (IC-HCL), Lyon, France.; Dalle S; ImmuCare, Cancer Institute of Hospices Civils de Lyon (IC-HCL), Lyon, France.; Dermatology Department, Lyon Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.; Orlova E; Endocrinology Research Centre, Institute of Paediatric Endocrinology, Moscow, Russia.; Frolova E; National Medical Research Center of Children's Health, Moscow, Russia.; Alba D; Diabetes Center, University of California, San Francisco, San Francisco, CA.; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Michels A; Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO.; Oftedal BE; University of Bergen, Bergen, Norway.; Department of Medicine, Haukeland University Hospital, Bergen, Norway.; Lionakis MS; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Husebye ES; Department of Medicine, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science and K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway.; Agarwal AK; Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX.; Li X; Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX.; Zhu C; Department of Immunology, UT Southwestern Medical Center, Dallas, TX.; Li Q; Department of Immunology, UT Southwestern Medical Center, Dallas, TX.; Oral E; Division of Metabolism, Endocrinology & Diabetes and Caswell Diabetes Institute, University of Michigan, Ann Arbor, MI.; Brown R; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.; Anderson MS; Diabetes Center, University of California, San Francisco, San Francisco, CA.; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Garg A; Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX.; DeRisi JL; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA.; Chan Zuckerberg Biohub, San Francisco, CA.
Source
Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE
Subject
Language
English
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.
(© 2022 by the American Diabetes Association.)
(© 2022 by the American Diabetes Association.)