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Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome)
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 s...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234012/ https://www.ncbi.nlm.nih.gov/pubmed/34205507 http://dx.doi.org/10.3390/ijms22126608 |
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author | Corvillo, Fernando González-Sánchez, Laura López-Lera, Alberto Arjona, Emilia Ceccarini, Giovanni Santini, Ferruccio Araújo-Vilar, David Brown, Rebecca J Villarroya, Joan Villarroya, Francesc Rodríguez de Córdoba, Santiago Caballero, Teresa Nozal, Pilar López-Trascasa, Margarita |
author_facet | Corvillo, Fernando González-Sánchez, Laura López-Lera, Alberto Arjona, Emilia Ceccarini, Giovanni Santini, Ferruccio Araújo-Vilar, David Brown, Rebecca J Villarroya, Joan Villarroya, Francesc Rodríguez de Córdoba, Santiago Caballero, Teresa Nozal, Pilar López-Trascasa, Margarita |
author_sort | Corvillo, Fernando |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8234012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82340122021-06-27 Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome) Corvillo, Fernando González-Sánchez, Laura López-Lera, Alberto Arjona, Emilia Ceccarini, Giovanni Santini, Ferruccio Araújo-Vilar, David Brown, Rebecca J Villarroya, Joan Villarroya, Francesc Rodríguez de Córdoba, Santiago Caballero, Teresa Nozal, Pilar López-Trascasa, Margarita Int J Mol Sci Article 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. MDPI 2021-06-21 /pmc/articles/PMC8234012/ /pubmed/34205507 http://dx.doi.org/10.3390/ijms22126608 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Corvillo, Fernando González-Sánchez, Laura López-Lera, Alberto Arjona, Emilia Ceccarini, Giovanni Santini, Ferruccio Araújo-Vilar, David Brown, Rebecca J Villarroya, Joan Villarroya, Francesc Rodríguez de Córdoba, Santiago Caballero, Teresa Nozal, Pilar López-Trascasa, Margarita Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome) |
title | Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome) |
title_full | Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome) |
title_fullStr | Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome) |
title_full_unstemmed | Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome) |
title_short | Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome) |
title_sort | complement factor d (adipsin) levels are elevated in acquired partial lipodystrophy (barraquer–simons syndrome) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234012/ https://www.ncbi.nlm.nih.gov/pubmed/34205507 http://dx.doi.org/10.3390/ijms22126608 |
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