Published on Tue Sep 28 2021

Perilipin-1 autoantibodies linked to idiopathic lipodystrophy in the setting of two distinct breaks in immune tolerance

Mandel-Brehm, C., Vazquez, S. E., Liverman, C., Cheng, M., Quandt, Z., Kung, A. F., Miao, B., Disse, E., Cugnet-Anceau, C., Dalle, S., Orlova, E., Frolova, E., Lionakis, M. S., Oftedal, B. E., Husebye, E. S., Anderson, M., DeRisi, J.

Background: 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. Methods: Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte specific lipid droplet protein Perilipin-1 in a murine model of Autoimmune Polyendocrine Syndrome 1 (APS1). We then tested for PLIN1 autoantibodies in human subjects with 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. Results: We identified autoantibodies to the lipid-droplet protein Perilipin-1 (PLIN1) in two human case reports including the first reported case of human APS1 with acquired lipodystrophy. Further, we extend PLIN1 autoantibodies to a second non-APS1 patient who acquired lipodystrophy as an immune-related adverse event following cancer immunotherapy. Conclusion: These data suggest that PLIN1 autoantibodies may represent a unifying marker of autoimmune lipodystrophy.