1. Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome)
- Author
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Margarita López-Trascasa, Giovanni Ceccarini, Teresa Caballero, Santiago Rodríguez de Córdoba, David Araújo-Vilar, Ferruccio Santini, Fernando Corvillo, Rebecca J. Brown, Laura González-Sánchez, Alberto López-Lera, Pilar Nozal, Joan Villarroya, Emilia Arjona, Francesc Villarroya, Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Instituto de Salud Carlos III, European Commission, Comunidad de Madrid, Asociación Española de Familiares y Afectados de Lipodistrofias, Xunta de Galicia, National Institute of Diabetes and Digestive and Kidney Diseases (US), Corvillo, Fernando, González-Sánchez, Laura, López-Lera, Alberto, Arjona, Emilia, Ceccarini, Giovanni, Santini, Ferruccio, Araújo-Vilar, David, Brown, Rebecca J., Villarroya, Francesc, Rodríguez de Córdoba, Santiago, Caballero, Teresa, Nozal, Pilar, López-Trascasa, Margarita, UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ), Corvillo, Fernando [0000-0001-6418-5647], González-Sánchez, Laura [0000-0002-4749-2423], López-Lera, Alberto [0000-0002-9596-6910], Arjona, Emilia [0000-0002-0753-3657], Ceccarini, Giovanni [0000-0003-0701-642X], Santini, Ferruccio [0000-0002-1706-0822], Araújo-Vilar, David [0000-0003-2852-7851], Brown, Rebecca J. [0000-0002-2589-7382], Villarroya, Francesc [0000-0003-1266-9142], Rodríguez de Córdoba, Santiago [0000-0001-6401-1874], Caballero, Teresa [0000-0003-3005-9858], Nozal, Pilar [0000-0002-8981-4312], and López-Trascasa, Margarita [0000-0001-8594-282X]
- Subjects
0301 basic medicine ,Male ,Lipodystrophy ,Adipose tissue ,Barraquer–Simons syndrome ,Acquired Partial Lipodystrophy ,Pathogenesis ,Cohort Studies ,0302 clinical medicine ,Complement Factor D ,Medicine ,Biology (General) ,Child ,Spectroscopy ,Acquired partial lipodystrophy ,General Medicine ,Ophthalmopathies ,Middle Aged ,Computer Science Applications ,Chemistry ,030220 oncology & carcinogenesis ,Adispin ,Female ,Oftalmopaties ,Adult ,medicine.medical_specialty ,Complement system ,Adolescent ,QH301-705.5 ,Medicina ,Complement factor D ,Acquired generalized lipodystrophy ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Young Adult ,Internal medicine ,Adipsin ,Aged ,Biomarkers ,Case-Control Studies ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,QD1-999 ,business.industry ,Organic Chemistry ,Adipose tissues ,medicine.disease ,Teixit adipós ,030104 developmental biology ,Endocrinology ,Alternative complement pathway ,sense organs ,business - Abstract
14 p.-7 fig.-2 tab., Complement overactivation has been reported in most patients with Barraquer–Simons 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 < 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’s 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., This study was funded by the Spanish Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund from the European Union (grant PI15-00255), by the Spanish Autonomous Region of Madrid (Complement II-CM network; S2017/BMD-3673), by the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP), by an intramural grant from the Xunta de Galicia (grant number ED431B 2020/37), and by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases.
- Published
- 2021