Autoantibodies to Perilipin-1 Define a Subset of Acquired Generalized Lipodystrophy
2 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
3 Institut de Cancérologie [Hospices civils de Lyon]
4 Département Endocrinologie-Diabétologie-Maladies Nutritionnelles [Lyon-Sud]
5 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
6 EASO / ERCM - Endocrinology Research Centre [Moscow, Russia] - Научно-исследовательский центр Институт эндокринологии
7 NMR2CH - National Medical Research Center of Children's Health [Moscow, Russia]
8 University of Colorado Anschutz Medical Campus [Aurora]
9 UiB - University of Bergen
10 Haukeland University Hospital
11 NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda]
12 University of Texas Southwestern Medical Center
13 UMich - Université du Michigan = University of Michigan [Ann Arbor]
14 National Institute of Child Health and Human Development [Bethesda]
15 Chan Zuckerberg BioHub [San Francisco, CA]
- Fonction : Auteur
- PersonId : 937229
- IdHAL : stephanedalle
- ORCID : 0000-0002-3423-4548
- IdRef : 075987279
Résumé
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.