Autoantibodies to Perilipin-1 Define a Subset of Acquired Generalized LipodystrophyCaleigh Mandel-Brehm, Sara E. Vazquez,, Christopher Liverman, Mickie Cheng, Zoe Quandt,, Andrew F. Kung, Audrey Parent, Brenda Miao,, Emmanuel Disse,, Christine Cugnet-Anceau,, Stephane 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, and Joseph L. DeRisi
Diabetes, Jan 2023Abstract: Acquired lipodystrophy is often characterized as an idio- pathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as auto- antibodies are generally lacking. Here, we used an unbi- ased proteome-wide screening approach to identify autoantibodies to the adipocyte-specific lipid droplet protein perilipin 1 (PLIN1) in a murine model of autoim- mune 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 as- say and indirect immunofluorescence on fat tissue. We identified autoantibodies to PLIN1 in these two cases, in- cluding the first reported case of APS1 with acquired lipodystrophy and a second patient who acquired lipo- dystrophy 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), particularly those with panniculitis and other features of autoimmunity. These data lend additional support to new literature that suggests that PLIN1 auto- antibodies represent a marker of acquired autoimmune lipodystrophies and further link them to a break in im- mune tolerance.
