All ultrasound scanning was performed by a single experienced vascular sonographer on the carotid arteries, using carotid duplex equipment (LOGIC E9)

All ultrasound scanning was performed by a single experienced vascular sonographer on the carotid arteries, using carotid duplex equipment (LOGIC E9). profile were associated with disease activity, the presence of anti-citrullinated proteins anti-bodies (ACPAs), and worse response to therapy in RA. AT Herbacetin in the context of arthritis is characterized by an inflammatory state alongside the infiltration of macrophages and B/plasmatic cells, where ACPAs can have a direct impact, inducing inflammation and insulin resistance in macrophages and promoting a defective adipocyte differentiation, partially restored by biologicals. Subject areas: Health sciences, Rheumatology, Immunology Graphical abstract Open in a separate window Highlights ? IR is related to disease activity, inflammation, and autoimmunity in RA patients ? IR state and adipocytokines might be associated with a worse response to biologics ? Visfatin could be used as a potential biomarker of subclinical atherosclerosis ? ACPAs might directly impact adipose tissue Health sciences; Rheumatology; Immunology. Introduction Rheumatoid arthritis (RA) is closely related to the development of cardiovascular and other metabolic comorbidities, such as insulin resistance (IR), type 2 diabetes mellitus, or obesity (Avi?a-Zubieta et?al., 2008; Chung et?al., 2008). In fact, RA patients might display an altered body composition since the early stages of the disease are often characterized by increased fat mass, pointing out to the adipose tissue (AT) as an important key organ regulator of outcomes in RA (Longo et?al., 2019). Our group has recently demonstrated that IR can be significantly higher in RA patients with a normal weight, suggesting that the chronic inflammatory state induced by RA mediates alterations in glucose and lipid metabolism associated with this disease (Arias-de la Rosa et?al., 2018). The dysregulation of the AT in RA has been manifested by the abnormal circulating levels of adipokines, which are molecules mainly produced by this organ. These molecules not only are involved in metabolic processes but also have been associated with the pathogenesis of RA, acting in effector cells and perpetuating inflammation (Del Prete et?al., 2014). However, to date, the relationship between adipokines and disease activity or autoimmunity is not completely understood yet. AT is mainly composed of adipocytes but also can contain other immune cells that influence the regulation of metabolic, Herbacetin endocrine, inflammatory, and immune activities (Del Prete et?al., 2014). The most abundant immune cells in AT are macrophages that, under inflammatory or metabolic alterations, can be polarized to an inflammatory phenotype recognized as the M1 state that has a profound effect on the inflammatory burden in this organ (Caslin et?al., 2020). In the subcutaneous AT of RA patients, the proportion of AT macrophages and their crown-like structures is increased and is related to the positivity of auto-antibodies, the systemic inflammatory markers, and the IR state (Giles et?al., 2018). More studies are necessary to completely understand the role of macrophages in the AT function in RA and to know the effects of auto-antibodies in the polarization state of macrophages. B cells can be accumulated in distinct fat depots such as visceral, subcutaneous, and brown AT (Srikakulapu et?al., 2020). Interestingly, B cells are one of the first immune cells infiltrated in the AT of obese mice and their key role in the obese-induced AT expansion has been suggested (DeFuria et?al., 2013; Winer et?al., 2011). Moreover, AT inflammation induced by B cells might lead to the release of pro-inflammatory immunoglobulins G (IgG) and cytokines into the circulatory system (Camell et?al., 2019; Hao et?al., 2011). In humans, it has recently been shown that the secretion Rabbit Polyclonal to Glucokinase Regulator of IgGs derived from B cells residents in subcutaneous AT led to the isotype class switching and the differentiation into plasma cells. Finally, the identification of elevated germinal B cells in human subcutaneous Herbacetin AT compared with peripheral blood cells in obesity could indicate that anti-bodies can be produced locally in this tissue (Frasca et?al., 2018). Taking into account the presence of auto-antibodies in RA and the evidence of the possible infiltration of B cells in the AT and the generation of anti-bodies on this tissue, it is feasible to think that autoimmunity can have a profound effect on the AT of RA patients, however, no study has evaluated the presence of B cells in the AT in the context Herbacetin of arthritis and the direct effect of the specific auto-antibodies for RA (anti-citrullinated proteins anti-bodies, ACPAs) on this organ and specifically in the cells that are Herbacetin composing it. There is a big gap in the knowledge.