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

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.

Adipsin Serum Concentrations and Adipose Tissue Expression in People with Obesity and Type 2 Diabetes

“…On the other hand, human studies found positive correlations between adipsin serum concentrations and BMI [21,26]. Interestingly, increased adipsin serum concentrations seem to be associated with acquired syndromic partial lipodystrophy [27].…”

Concentration of Selected Adipokines and Factors Regulating Carbohydrate Metabolism in Patients with Head and Neck Cancer in Respect to Their Body Mass Index

“…Adipsin, also called complement factor D, is a serine protease secreted mainly by adipocytes. It functions as an activator of the alternative pathway of the complement system [ 52 ]. Increased BMI and a greater volume of adipose tissue are associated with a high level of adipsin [ 53 ].…”

Functional Identification of Complement Factor D and Analysis of Its Expression during GCRV Infection in Grass Carp (Ctenopharyngodon idella)

“…Df, a member of the chymotrypsin family of serine proteases, plays a pivotal role in both initiation and amplification loops of complement system activation by continuously promoting C3 cleavage in the AP [ 60 , 61 ]. It has been reported in many human and mouse disease models that the deficiency or dysfunction of Df weakens the host immune killing ability to foreign pathogens, including viruses and bacteria [ 8 , 27 , 28 , 29 , 62 , 63 ]. There is also substantial evidence that Df mRNA expression is upregulated after pathogen infection in various fish species such as O. fasciatus [ 36 ], M. amblycephala [ 37 ], and C. auratus [ 38 ], suggesting its importance in fish immune defense.…”