{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:05:37Z","timestamp":1791925537849,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15-00255"],"award-info":[{"award-number":["PI15-00255"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Autonomous Region of Madrid","award":["Complement II-CM network; S2017\/BMD-3673"],"award-info":[{"award-number":["Complement II-CM network; S2017\/BMD-3673"]}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431B 2020\/37"],"award-info":[{"award-number":["ED431B 2020\/37"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Complement overactivation has been reported in most patients with Barraquer\u2013Simons syndrome (BSS), a rare form of acquired partial lipodystrophy. Complement Factor D (FD) is a serine protease with a crucial role in the activation of the alternative pathway of the complement system, which is mainly synthesized by adipose tissue. However, its role in the pathogenesis of BSS has not been addressed. In this study, plasma FD concentration was measured in 13 patients with BSS, 20 patients with acquired generalized lipodystrophy, 22 patients with C3 glomerulopathy (C3G), and 50 healthy controls. Gene expression and immunohistochemistry studies were assayed using atrophied adipose tissue from a patient with BSS. We found significantly elevated FD levels in BSS cases compared with the remaining cohorts (p &lt; 0.001). There were no significant differences in FD levels between sexes but FD was strongly and directly associated with age in BSS (r = 0.7593, p = 0.0036). A positive correlation between FD and C3 was seen in patients with C3G, characterized by decreased FD levels due to chronic C3 consumption, but no correlation was detected for BSS. Following mRNA quantification in the patient\u2019s adipose tissue, we observed decreased CFD and C3 but elevated C5 transcript levels. In contrast, the increased FD staining detected in the atrophied areas reflects the effects of persistent tissue damage on the adipose tissue, thus providing information on the ongoing pathogenic process. Our results suggest that FD could be a reliable diagnostic biomarker involved in the pathophysiology of BSS by promoting unrestrained local complement system activation in the adipose tissue environment.<\/jats:p>","DOI":"10.3390\/ijms22126608","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T04:21:21Z","timestamp":1624249281000},"page":"6608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer\u2013Simons syndrome)"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6418-5647","authenticated-orcid":false,"given":"Fernando","family":"Corvillo","sequence":"first","affiliation":[{"name":"Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4749-2423","authenticated-orcid":false,"given":"Laura","family":"Gonz\u00e1lez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"L\u00f3pez-Lera","sequence":"additional","affiliation":[{"name":"Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Arjona","sequence":"additional","affiliation":[{"name":"Center for Biomedical Network Research on Rare Diseases, 28029 Madrid, Spain"},{"name":"Department of Molecular Biomedicine, Margarita Salas Center for Biological Research, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0701-642X","authenticated-orcid":false,"given":"Giovanni","family":"Ceccarini","sequence":"additional","affiliation":[{"name":"Obesity and Lipodystrophy Center at the Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruccio","family":"Santini","sequence":"additional","affiliation":[{"name":"Obesity and Lipodystrophy Center at the Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, 56126 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":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15703 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J","family":"Brown","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Villarroya","sequence":"additional","affiliation":[{"name":"Departament de Bioquimica I Biomedicina Molecular, Institut de Biomedicina de la Universitat de Barcelona, 08007 Barcelona, Catalonia, Spain"},{"name":"CIBER Fisiopatolog\u00eda de La Obesidad Y Nutrici\u00f3n, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Villarroya","sequence":"additional","affiliation":[{"name":"Departament de Bioquimica I Biomedicina Molecular, Institut de Biomedicina de la Universitat de Barcelona, 08007 Barcelona, Catalonia, Spain"},{"name":"CIBER Fisiopatolog\u00eda de La Obesidad Y Nutrici\u00f3n, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6401-1874","authenticated-orcid":false,"given":"Santiago","family":"Rodr\u00edguez de C\u00f3rdoba","sequence":"additional","affiliation":[{"name":"Center for Biomedical Network Research on Rare Diseases, 28029 Madrid, Spain"},{"name":"Department of Molecular Biomedicine, Margarita Salas Center for Biological Research, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3005-9858","authenticated-orcid":false,"given":"Teresa","family":"Caballero","sequence":"additional","affiliation":[{"name":"Center for Biomedical Network Research on Rare Diseases, 28029 Madrid, Spain"},{"name":"Department of Allergy, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ), 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8981-4312","authenticated-orcid":false,"given":"Pilar","family":"Nozal","sequence":"additional","affiliation":[{"name":"Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases, 28029 Madrid, Spain"},{"name":"Immunology Unit, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"L\u00f3pez-Trascasa","sequence":"additional","affiliation":[{"name":"Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Department of Medicine, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"ref_1","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. 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