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Large-vessel vasculitides (LVV) comprise a group of chronic inflammatory diseases of the aorta and its major branches. The most common forms of LVV are giant cell arteritis (GCA) and Takayasu arteritis (TAK). Both GCA and TAK are characterized by granulomatous inflammation of the vessel wall accompanied by a maladaptive immune and vascular response that promotes vascular damage and remodeling. The inflammatory process in LVV starts in the adventitia where fibroblasts constitute the dominant cell population. Fibroblasts are traditionally recognized for synthesizing and renewing the extracellular matrix thereby being major players in maintenance of normal tissue architecture and in tissue repair. More recently, fibroblasts have emerged as a highly plastic cell population exerting various functions, including the regulation of local immune processes and organization of immune cells at the site of inflammation through production of cytokines, chemokines and growth factors as well as cell-cell interaction. In this review, we summarize and discuss the current knowledge on fibroblasts in LVV. Furthermore, we identify key questions that need to be addressed to fully understand the role of fibroblasts in the pathogenesis of LVV., Competing Interests: Declaration of competing interest Kornelis S.M. van der Geest received speaking fee from Roche, and research support from AbbVie and Siemens Healthineers. Other authors had no conflicts of interest to declare. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Kornelis S.M. van der Geest reports a relationship with Roche that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Giant cell arteritis (GCA) is a granulomatous vasculitis affecting large arteries, especially the aorta and the extracranial branches of the external carotid artery. Its exact pathogenesis is not fully understood but major progress has been made in recent years, leading to new therapeutic targets like inhibition of the interleukin-6 pathway or the modulation of immune checkpoints. The cause of GCA has not been clearly identified but it is thought that GCA occurs on a genetic background and is triggered by unknown environmental factors that could activate and lead to the maturation of dendritic cells localized in the adventitia of normal arteries. These activated dendritic cells then produce chemokines which trigger the recruitment of CD4 + T cells, which in turn become activated, proliferate and polarize into Th1 and Th17 cells, which produce IFN-γ and IL-17, respectively. Exposed to IFN-γ, endothelial cells and vascular smooth muscle cells produce chemokines leading to the recruitment of further Th1 cells, CD8 + T cells and monocytes. The latter differentiate into macrophages, which, when persistently exposed to IFN-γ, form giant cells, the histological hallmark of GCA. With the contribution of vascular smooth muscle cells, immune cells then trigger the destruction and remodeling of the arterial wall, thus leading to the formation of a neo-intima resulting in progressive occlusion of the arterial lumen, which is responsible for the ischemic symptoms of GCA. In this paper, we review recent progress in our understanding of GCA pathogenesis in the fields of genetics, epigenetics, infections, immunology and vascular remodeling., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The effect of the number of copies in the SMN1 and SMN2 genes - the most extensively studied susceptibility and modifying genetic factors in adult onset motor neuron diseases - as a genetic risk factor for Hirayama's disease (HirD) has never been studied. The purpose of this study was to investigate the influence of the number of copies of the SMN1/SMN2 genes on the resulting phenotype in 13 HirD Spanish patients., Patients and Methods: We performed a qualitative and quantitative SMN1/SMN2 gene analysis in 13 unrelated HirD patients. The phenotype-genotype correlation was investigated, paying particular attention to the effect of the SMN1/SMN2 copy number on the disease's phenotype., Results: No patient had a homozygous deletion of the SMN1 or SMN2. No differences were found when comparing the SMN1 and SMN2 copy number distributions of the healthy population and HirD patients, and they do not therefore appear to be a susceptibility factor. There was also no correlation found between the number of copies of the SMN1 and SMN2 and the severity of the resulting phenotype., Conclusion: Our results suggest that SMN1 and SMN2 are not predisposing factors for HirD and therefore support a lack of association between these genes and the resulting phenotype.

Background: SOD1 gene mutations are the most common identified cause of ALS, accounting for approximately 20% of familial ALS cases and around 4% of sporadic ALS cases. However, the prevalence of SOD1 varies in different ethnic groups. No previous epidemiological studies have been carried out in Catalonia., Objective: To determine the prevalence of SOD1 gene mutations in a Catalan ALS population, and to analyze the genotype-phenotype relationship., Materials and Methods: 30 different FALS pedigrees and 94 sporadic ALS patients were screened for SOD1 mutations using direct sequence analysis., Results: Five of the 30 FALS pedigrees (16.6%) carried a SOD1 mutant. The mutations identified in this group were G37R, D76V, S105L, I112M and N139H. Four SOD1 mutants (4.25%) were found in the sporadic ALS group (SALS). The overall frequency (FALS plus SALS) of SOD1 mutations in our series was 6.45%. In the SALS group, D90A was identified in a patient presenting the typical Scandinavian phenotype. A 53-year-old woman with no family history of ALS carried the N139H mutation. Two unrelated sporadic ALS cases carried the A140A SOD1 mutant., Conclusions: The prevalence of the SOD1 mutation in FALS in Catalonia is similar to levels in other Mediterranean countries, but lower than those in reports studying the Belgian, Japanese, and Scottish populations. The prevalence of the SOD1 mutation was 4.25% in patients with no family history of ALS. These results may have significant repercussions on genetic counseling, and screening for the SOD1 mutation in sporadic ALS cases must therefore be considered.