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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.

49 p.-2 fig.-2 tab., Genetic variability in the complement system and its association with disease has been known for more than 50 years, but only during the last decade have we begun to understand how this complement genetic variability contributes to the development of diseases. A number of reports have described important genotype-phenotype correlations that associate particular diseases with genetic variants altering specific aspects of the activation and regulation of the complement system. The detailed functional characterization of some of these genetic variants provided key insights into the pathogenic mechanisms underlying these pathologies, which is facilitating the design of specific anti-complement therapies. Importantly, these analyses have sometimes revealed unknown features of the complement proteins. As a whole, these advances have delineated the functional implications of genetic variability in the complement system, which supports the implementation of a precision medicine approach based on the complement genetic makeup of the patients. Here we provide an overview of rare complement variants and common polymorphisms associated with disease and discuss what we have learned from them., SRdeC is supported by the Spanish “Ministerio de Economía y Competitividad/FEDER” [SAF2015-66287-R] and the Autonomous Region of Madrid [S2017/BMD-3673]. SRdeC is member of the "CIB Intramural Program “Molecular Machines for Better Life” (MACBET)". MLT is supported by the Spanish “Ministerio de Economía y Competitividad/FEDER” [PI15-00255]. EGdeJ is supported by the Spanish “Ministerio de Economía y Competitividad/FEDER” [SAF2014-52339-P]. SRdeC and EGdeJ are also supported by the “Fundación Inocente Inocente” (Madrid, Spain).