{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:18:22Z","timestamp":1789431502250,"version":"build-2803163510"},"reference-count":28,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:p>Acquired generalized lipodystrophy (AGL) is a rare condition characterized by massive loss of adipose tissue through the body, causing severe metabolic complications. Autoimmune destruction of adipocytes is strongly suspected based on the frequent association of AGL with autoimmune disorders. In 2018, autoantibodies against perilipin 1 (PLIN1) were identified in three patients with autoimmune-associated AGL. However, the pathogenic mechanism and clinical impact of anti-PLIN1 remain unsolved. The prevalence of anti-PLIN1 autoantibodies in an AGL cohort of 40 patients was 50% (20 of 40). Among positive patients, 10 had the autoimmune variety and 10 had panniculitis-associated AGL. The IgG isotype was predominant, although some IgM antibodies were detected. Epitope-mapping studies did not identify a single, major epitope. Instead, autoantibodies typically bound to several different peptides, among which the central (233\u2013405) domain was detected in all antibody-positive patients, for both IgG and IgM autoantibodies. In-depth epitope mapping indicated that anti-PLIN1 autoantibodies predominantly recognize the \u03b1\u03b2-hydrolase domain containing 5 (ABHD5) binding site (383\u2013405). Autoantibodies dose-dependently blocked the binding of PLIN1 to ABHD5 and caused a dislocation of ABHD5 toward the cytosol, leading to an increase in lipolysis and lipase activities. Finally, anti-PLIN1 titers significantly correlated with the amount of fat loss, metabolic control impairment, and severity of liver injury. Our data strongly support that anti-PLIN1 autoantibodies are a diagnostic biomarker and a cause of lipodystrophy in patients with AGL.<\/jats:p>","DOI":"10.2337\/db21-1086","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T18:32:42Z","timestamp":1656613962000},"page":"71-84","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":33,"title":["Characterization and Clinical Association of Autoantibodies Against Perilipin 1 in Patients With Acquired Generalized Lipodystrophy"],"prefix":"10.2337","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6418-5647","authenticated-orcid":false,"given":"Fernando","family":"Corvillo","sequence":"first","affiliation":[{"name":"1Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain"},{"name":"2Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Magno","sequence":"additional","affiliation":[{"name":"4Obesity and Lipodystrophy Center, Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruccio","family":"Santini","sequence":"additional","affiliation":[{"name":"4Obesity and Lipodystrophy Center, Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2852-7851","authenticated-orcid":false,"given":"David","family":"Ara\u00fajo-Vilar","sequence":"additional","affiliation":[{"name":"5UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine (Medicine Area), Center for Research in Molecular Medicine and Chronic Diseases 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"L\u00f3pez-Trascasa","sequence":"additional","affiliation":[{"name":"1Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain"},{"name":"7Departamento de Medicina, Universidad Aut\u00f3noma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"2022122018592436700_B1","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1210\/jc.2016-2466","article-title":"The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline","volume":"101","author":"Brown","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"2022122018592436700_B2","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1210\/jcem.87.5.8624","article-title":"Serum adiponectin and leptin levels in patients 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