Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).

Fernando Corvillo,Laura González-Sánchez,Margarita López-Trascasa,David Araújo-Vilar,Santiago Rodríguez De Córdoba,Francesc Villarroya,Joan Villarroya,Pilar Nozal,Emilia Arjona,Teresa Caballero,Ferruccio Santini,Giovanni Ceccarini,Rebecca J Brown,Alberto López-Lera

doi:10.3390/ijms22126608

Abstract

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.

Highlights

Lipodystrophies are a heterogeneous group of rare disorders characterized by the loss of adipose tissue [1]
Factor D (FD) levels were significantly elevated in patients with Barraquer–Simons syndrome (BSS) compared with individuals from the control, acquired generalized lipodystrophy (AGL) and C3 glomerulopathy (C3G) cohorts (BSS: median 1.530 μg/mL (IQR—1.425–1.940); controls: 1.185 μg/mL (1.025–1.423); AGL: 0.905 μg/mL (0.753–1.125); C3G: 1.115 μg/mL (0.705–1.570); p < 0.05 for controls and C3G, and p < 0.001 for AGL) (Figure 1)
We found that plasma FD levels are significantly higher in a representative cohort of patients with BSS compared with controls and another two cohorts composed of patients with AGL and C3G

Summary

Introduction

Lipodystrophies are a heterogeneous group of rare disorders characterized by the loss of adipose tissue [1]. There are multiple subtypes of lipodystrophies, which can be congenital or acquired and which in turn vary in the distribution of adipose tissue loss, being partial, generalized, or localized. One of these diseases is Barraquer–Simons syndrome (BSS; ORPHA:79087), an acquired form of partial lipodystrophy characterized by bilateral symmetrical loss of adipose tissue at upper body locations [1]. In most of the published cohorts of patients with BSS, C3NeF is the most frequent antibody (70%) [2,4], our group has described the existence of additional autoantibodies against AP proteins [2]. Mathieson et al evidenced that C3NeF could lyse adipocytes [5]

Methods

Results

Conclusion