80cda33c70d0cbe5c098e18d9289f65d  pmc_34205507.pdf
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22802a3fe972d06e27a43945e84bb886a565bc2806ccbd2ce4d52a50073c6046  pmc_34205507.pdf

Title:           Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome)
Subject:         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.
Keywords:        adipsin; complement factor D; acquired partial lipodystrophy; Barraquer–Simons syndrome; complement system
Author:          Fernando Corvillo, Laura González-Sánchez, Alberto López-Lera, Emilia Arjona, Giovanni Ceccarini, Ferruccio Santini, David Araújo-Vilar, Rebecca J Brown, Joan Villarroya, Francesc Villarroya, Santiago Rodríguez de Córdoba, Teresa Caballero, Pilar Nozal and Margarita López-Trascasa
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 Date: 2024-10-02 03:12:12 CEST
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     Item: 
      Title: Introduction 
      Destination: section.1
     Item: 
      Title: Results 
      Destination: section.2
      Children: 
       Item: 
        Title: Circulating FD Levels Are Increased in Patients with BSS 
        Destination: subsection.2.1
       Item: 
        Title: FD Levels Are a Potentially Reliable Biomarker for the Diagnosis of BSS 
        Destination: subsection.2.2
       Item: 
        Title: Age- and Sex-Related Differences in FD Levels 
        Destination: subsection.2.3
       Item: 
        Title: Effects of Complement System Activation on Plasma FD Levels 
        Destination: subsection.2.4
       Item: 
        Title: Increased FD Labelling at Lipoatrophic Areas 
        Destination: subsection.2.5
     Item: 
      Title: Discussion 
      Destination: section.3
     Item: 
      Title: Materials and Methods 
      Destination: section.4
      Children: 
       Item: 
        Title: Study Cohorts 
        Destination: subsection.4.1
       Item: 
        Title: Biological Samples 
        Destination: subsection.4.2
       Item: 
        Title: Complement System Determinations 
        Destination: subsection.4.3
       Item: 
        Title: Measurement of FD in Plasma by ELISA 
        Destination: subsection.4.4
       Item: 
        Title: Western Blot Analysis 
        Destination: subsection.4.5
       Item: 
        Title: RNA Extraction and qRT-PCR 
        Destination: subsection.4.6
       Item: 
        Title: Immunohistochemical Staining 
        Destination: subsection.4.7
       Item: 
        Title: Statistical Analysis 
        Destination: subsection.4.8
     Item: 
      Title: References
      Destination: subsection.4.8
   Info: 
    Title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer Simons syndrome)
    Author: Fernando Corvillo, Laura González-Sánchez, Alberto López-Lera, Emilia Arjona, Giovanni Ceccarini, Ferruccio Santini, David Araújo-Vilar, Rebecca J Brown, Joan Villarroya, Francesc Villarroya, Santiago Rodríguez de Córdoba, Teresa Caballero, Pilar Nozal and Margarita López-Trascasa
    Subject: 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.
    Keywords: adipsin; complement factor D; acquired partial lipodystrophy; Barraquer Simons syndrome; complement system
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  Checksum: 64b1e1b1
   Type: CRC32
  Checksum: 80cda33c70d0cbe5c098e18d9289f65d
   Type: MD5
  Checksum: 9e1d06d38d81c4229e3435eaad4cd3a92459145a
   Type: SHA-1
  Checksum: 22802a3fe972d06e27a43945e84bb886a565bc2806ccbd2ce4d52a50073c6046
   Type: SHA-256