Ana Suarez

University of Oviedo | UNIOVI · Department of Functional Biology

Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of these alterations seems to be associated with misbalanced immunological parameter levels. However, it is still unclear as to which immunological parameter...

Background Type I Interferon (IFN) pathway activation plays a central role in the pathogenesis of several autoimmune conditions. However, limited evidence is available on the IFN pathway activation in antiphospholipid antibody (aPL) positive subjects, including aPL carriers and antiphospholipid syndrome (APS) patients. In addition, recent evidences...

Background cardiovascular (CV) risk excess in rheumatoid arthritis (RA) cannot be solely attributed to traditional CV risk factors. Chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis development in RA. Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL) and its componen...

Dear Editor, We would like to thank our colleagues Drs Pagano and Vuilleumier for their insightful commentary [1] on our article [2]. In this reply, we address the points raised by the authors in order to promote and expand scientific discussion, and guide the readers on these topics. Pagano and Vuilleumier made a point regarding the need to includ...

Objective Chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis in rheumatoid arthritis (RA). Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL). This study aimed to characterize the specificity, clinical relevance and emergence of humoral responses against HDL along dise...

Objective chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis in rheumatoid arthritis (RA). Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL). However, their specificity, clinical relevance and emergence along disease course are unknown, especially during the earliest...

Background vascular insult accounts for the cardiovascular (CV) risk excess in rheumatoid arthritis (RA). Angiogenic T cells (Tang), which are responsible of vascular repair, have been described to be reduced in established RA with overt CV disease. However, whether Tang are altered during the earliest stage of the disease and related to subclinica...

Background Type I Interferons (IFN) are central players in the pathogenesis, disease activity and evolution of several autoimmune conditions. To date, a limited number of evidences is available on the specific role of IFN activation in antiphospholipid antibodies (aPL) positive patients, including aPL carriers, primary antiphospholipid syndrome (PA...

High Density Lipoprotein (HDL) plays a protective role in abdominal aortic aneurysm (AAA); however, recent findings suggest that oxidative modifications could lead to dysfunctional HDL in AAA. This study aimed at testing the effect of oxidized HDL on aortic lesions and humoral immune responses in a mouse model of AAA induced by elastase, and evalua...

Background and Aims: Alterations in novel immune cell subsets, such as angiogenic T cells (Tang), senescent T cells (CD4 ⁺ CD28 null ), and monocyte subsets are associated with impaired vascular homeostasis in several inflammatory conditions. However, mediators underlying vascular deterioration in chronic kidney disease (CKD) are poorly characteriz...

During the last decades the gut microbiota has been identified as a key mediator in the diet-health interaction. However, our understanding on the impact of general diet upon microbiota is still limited. Dietary indices represent an essential approach for addressing the link between diet and health from a holistic point of view. Our aim was to test...

Objective: To quantify the levels of circulating exosomes derived from T-cells and monocytes and their possible associations with leukocyte subpopulations and cytokine milieu in Systemic Lupus Erythematosus (SLE). Methods: Total circulating exosomes (CD9 ⁺ -Ex) and those derived from T-cells (CD3 ⁺ -Ex) and monocytes (CD14 ⁺ -Ex) were quantified by...

Objective: eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting an enhanced metabolization, the role of oxylipins in disease stratification remains unexplored. This study aims to characteriz...

This study aimed at evaluating the clinical relevance of glycoprotein profiles during the earliest phases of rheumatoid arthritis (RA) as biomarkers of cardiovascular (CV) risk and treatment response. Then, GlycA and GlycB serum levels were measured using 1H-nuclear magnetic resonance in 82 early RA patients, 14 clinically-suspect arthralgia (CSA),...

Background Type I Interferons (IFN) play a key role in the pathogenesis and development of various autoimmune conditions. Among them, a solid amount of data demonstrates that the expression of various IFN regulated genes (IRGs), the so-called “IFN signature”, has been linked to disease activity and disease progression in systemic lupus erythematosu...

Background and Aims The stratification of early cardiovascular (CV) risk is a major unmet need in chronic kidney disease (CKD). Since angiogenic T-cells are emerging mediators of vascular homeostasis and have been linked to CV disease (CVD), this study evaluated the frequency of circulating angiogenic T-cells in CKD patients undergoing peritoneal d...

Background traditional approaches and lipidomics support the relevance of eicosanoids in rheumatic conditions, such as rheumatoid arthritis (RA). Previous studies from our group and others have revealed altered levels of arachidonic acid in RA, pointing to a possible consumption or enhanced metabolisation. However, the potential alterations of its...

Objective: The aim was to evaluate the most relevant cell populations involved in vascular homeostasis as potential biomarkers of SLE-related cardiovascular disease (CVD). Methods: Low-density granulocytes (LDGs), monocyte subsets, endothelial progenitor cells, angiogenic T (Tang) cells, CD4+CD28null and Th1/Th17 lymphocytes and serum cytokine l...

Objectives: TLR3 mediates skin solar injury by binding nuclear material released from apoptotic keratinocytes, resulting in the production of pro-inflammatory cytokines. Because the TLR3 gene is located in 4q35, a known systemic lupus erythematosus (SLE) susceptibility locus, we wondered whether TLR3 single nucleotide polymorphisms (SNPs) were ass...

Background Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. Dye-based chromoendoscopy (CE) is the currently recommended method for the detection of dysplasia in IBD surveillance colonoscopy; the role of virtual chromoendoscopy (VCE) is not yet well defined. To compare CE with VCE using iSCAN1 digital image...

High-density lipoproteins cholesterol (HDLc) levels are decreased in abdominal aortic aneurysm (AAA), which is hallmarked by autoimmunity and lipid aortic deposits. To investigate whether IgG anti-HDL antibodies were present in AAA and their potential association with clinical features, IgG anti-HDL and total IgG along with HDLc plasma levels were...

Inflammation is central to chronic kidney disease (CKD) pathogenesis and vascular outcomes, but the exact players remain unidentified. Since low density granulocytes (LDGs) are emerging mediators in inflammatory conditions, we aimed to evaluate whether LDGs may be altered in CKD and related to clinical outcomes as biomarkers. To his end, LDGs subse...

Introduction: Recurrent thrombotic events are a hallmark of Antiphospholipid Syndrome (APS). However, biomarkers to identify if a patient with antiphospholipid antibodies (aPL) is at higher risk to develop an arterial or a venous event are lacking. Recently, the pathogenic role of anti-high-density lipoproteins antibodies (anti-HDL) in the occurren...

Objective: The aim was to evaluate whether T cell subsets and the lipid profile could be linked to the cardioprotective effect of IgM anti-phosphorylcholine (PC) antibodies in SLE. Methods: Anti-PC antibodies were quantified by ELISA in 197 patients and 99 controls and analysed in relationship to clinical features, treatments and serum lipids. C...

Background monocytes are largely recognized as drivers of the atherosclerosis development, the leading determinant of cardiovascular (CV) morbidity in rheumatoid arthritis (RA). Far from being a unique population, functionally and phenotypically subpopulations can be distinguished, although their relevance to CV disease is uncertain. Recently, the...

Background Angiogenic T cells (Tang) are responsible of vascular repair and homeostasis. Decreased Tang frequencies have been reported in rheumatoid arthritis (RA), in association with disease activity and previous history of cardiovascular (CV) disease. However, excess of CV risk is already present during the early stage of RA. Whether Tang cells...

Emerging evidence suggests a role for 7-dehydrocholesterol reductase (DHCR7) in the crosstalk between cholesterol and vitamin D. Our aim was to evaluate the impact of vitamin D-related polymorphisms and DHCR7 levels in the association between vitamin D deficiency and altered lipid profile in rheumatoid arthritis (RA). Serum 25(OH)-vitamin D, DHCR7...

Background Despite vaccination against measles virus, outbreaks of this infection have been reported in western European countries. Little is known about measles virus serological status in adult patients with inflammatory bowel disease (IBD). On the other hand, few studies have analysed factors related to measles virus immune status. Our aim was t...

Background Screening and treatment of latent tuberculosis infection (LTBI) before starting biological therapy in patients with inflammatory bowel disease (IBD) has decreased the risk of active tuberculosis. However, among patients with a negative baseline screening there is still a risk of developing tuberculosis. Positive conversion of tuberculin...

Introduction: Overactivation of the type I interferon (IFN) signature has been observed in several systemic autoimmune conditions, such as Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA). Impaired control of Interferon-Responding Genes (IRGs) expression by their regulatory mechanisms, including Interferon Regulatory Factors (IRFs),...

Serum free fatty acids (FFA) are generally elevated in obesity. The gut microbiota is involved in the host energy metabolism through the regulation of body fat storage, and a link between diet, FFA and the intestinal microbiota seems to exist. Our aim was to explore the interaction among serum FFA levels, gut microbiota, diet and obesity through a...

Introduction: B-cell activation is pivotal in rheumatoid arthritis (RA) pathogenesis and represents a relevant therapeutic target. The main aim of this study was to characterize the profiles of B-cell factors and their decoy receptors in RA and evaluate their clinical relevance. Methods: sBLyS, sAPRIL, sBCMA, sTACI, sBLyS-R, and several cytokines'...

Background and aims: Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the asso...

Although most of the health effects attributed to polyphenols may be linked to their phenolic-derived metabolites, the role of the intestinal derived-phenolics in human health is still far from being well understood. We determined the profile of fecal phenolic-derived metabolites, microbiota, biomarkers of oxidative stress and inflammation, and dai...

Introduction: The role of the human intestinal microbiota in the maintenance of a healthy physiological condition, as well as its relation to the development of disease, remains to be clarified. Current evidence suggests that intestinal microbes could be involved in the initiation and amplification of autoimmune diseases, including rheumatoid arthr...

Background rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) risk. Although vitamin D deficiency has been linked to CV disease in other conditions, studies in RA have yielded contradictory results and pointed to the involvement of additional factors. On the one hand, several genetic polymorphisms have been linked to vitamin...

Background cardiovascular (CV) disease morbidity is increased in inflammatory joint diseases (IJD), as rheumatoid (RA) and psoriatic arthritis (PsA). Whereas accelerated subclinical atherosclerosis and endothelial dysfunction have been widely studied, less attention has been paid to myocardial function. RA patients with established disease who deve...

Background increased cardiovascular (CV) risk in inflammatory joint diseases (IJD) such as rheumatoid (RA) or psoriatic arthritis (PsA) is linked to an impaired vascular homeostasis. Chronic inflammation and immune dysregulation prompt endothelial damage and impair reparative mechanisms. Among them, circulating CD34 +bone marrow-derived progenitors...

Background increased expression of interferon-responding genes (IRGs), the so-called IFN signature, has been reported in rheumatoid arthritis (RA) in peripheral blood and synovial tissue. However, some controversy exists concerning its clinical relevance, since longitudinal changes of the IFN signature have been reported upon different treatments a...

IntroductionImpaired high-density lipoprotein (HDL) levels and antioxidant functionality of HDL, mainly attributed to a decreased paraoxonase-1 (PON1) functionality, have been described in autoimmune conditions. In this setting, a role for humoral response in cardiovascular disease is emerging. This study evaluates the role of immunoglobulin G (IgG...

Introduction: Impaired high-density lipoprotein (HDL) levels and antioxidant functionality of HDL, mainly attributed to a decreased paraoxonase-1 (PON1) functionality, have been described in autoimmune conditions. In this setting, a role for humoral response in cardiovascular disease is emerging. This study evaluates the role of immunoglobulin G (I...

Background and aims: Cardiovascular (CV) morbidity is increased in inflammatory joint diseases (IJD), as rheumatoid (RA) and psoriatic arthritis (PsA). Whereas increased prevalence of subclinical atherosclerosis has been reported in these conditions, whether an early myocardial functionality is also impaired remains unknown. The aim of this study...

Introduction An increased expression of interferon (IFN)-responding genes (IRGs), the so-called IFN signature, has been reported in rheumatoid arthritis (RA). However, some controversy exists concerning its clinical relevance. The main aim of this study is to evaluate whether quantitative and qualitative differences in the activation of the IFN pat...

Background Retrospective studies performed with databases have shown that herpes zoster infection (HZ) is more frequent in patients with inflammatory bowel disease (IBD) than in the general population. To know the risk of this infection and its complications is important, especially before the introduction of JAK inhibitors into the therapeutic ars...

Background The presence of anti-Saccharomyces Cerevisiae antibodies (ASCA) in patients with Crohn’s disease (CD) has been related to having presented stricturing or penetrating complications. Little is known about its utility in predicting the development of complicated behaviour in the future. Our aim is to evaluate the possible value of ASCA dete...

The present study aimed to evaluate the possible role of immunoglobulin G (IgG) antibodies against high-density lipoproteins (HDL) and paraoxonase 1 (PON1) as possible biomarkers of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). To this end, levels of these autoantibodies, PON1 activity and total antioxidant capacity were quant...

Background: Systemic lupus erythematosus (SLE) is a chronic infl ammatory disease of autoimmune nature, in which oxidative stress is implicated. Aim: Compare the concentrations of dietary and blood antioxidants, as well as gut microbiota, with serum malondialdehyde (MDA) and C reactive protein (CRP) in 21 subjects suffering from non-active syste...

A growing body of evidence highlights the relevance of free fatty acids (FFA) for human health, and their role in the cross talk between the metabolic status and immune system. Altered serum FFA profiles are related to several metabolic conditions, although the underlying mechanisms remain unclear. Recent studies have highlighted the link between g...

Background: Cardiovascular (CV) risk stratification is suboptimal if solely based on traditional CV risk factors, since individuals with similar risk profiles could exhibit diverging CV outcomes. Thus, there is a need for new risk factors to be identified. Recent studies emphasize the relevance of the endothelial homeostasis in the control of CV r...

Background the interactions between inflammation and lipid profile in rheumatoid arthritis (RA) are poorly understood. The lipid profile study in RA has been biased towards lipoprotein levels, whereas those of triglycerides (TG) and lipoprotein functionality have been underestimated. Objetives since recent findings suggest a role for TG and TG-ric...

Background the interactions between inflammation and lipid profile in RA are poorly understood. The study of lipid profiles in RA has been biased towards lipoprotein levels, whereas those of triglycerides (TG) and lipoprotein functionality have been neglected. Objectives since recent findings point to an emerging role for TG and TG-rich lipoprotei...

Background studies on B cell-mediated autoimmune diseases highlight the relevance of the B Lymphocyte Stimulator (BLyS) and A Proliferation-Inducing Ligand (APRIL), but emerging evidence points to an interaction with cell lineages other than B subsets. Although disturbances in the B cell compartment underlie the early stages of rheumatoid arthritis...

From the discovery of Endothelial Progenitor Cells (EPC), these bone marrow-derived precursors have been placed as crucial mediators of the endothelial repair. Accordingly, altered levels and function of EPC have been found in different scenarios of CV risk. Despite the fact that EPC exhibit important characteristics which support a link of this ce...

Background Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the r...

\textbf{BACKGROUND}$: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting...

Background Immune cells under chronic inflammation shed microparticles (MPs) that could fuel the inflammatory responses and atherosclerosis typically presented in systemic lupus erythematosus (SLE). This study analyzes total and subset-specific MPs from SLE patients and their possible influence on clinical features, leukocyte activation and serum c...

Metabolic impairments are a frequent hallmark of systemic lupus erythematosus (SLE). Increased serum levels of free fatty acids (FFA) are commonly found in these patients, although the underlying causes remain elusive. Recently, it has been suggested that factors other than inflammation or clinical features may be involved. The gut microbiota is kn...

Background: Traditional and non-traditional cardiovascular (CV) risk factors underlie CV disease occurrence in rheumatoid arthritis (RA). Recently, a functional impairment of HDL has been observed. Although the actual players are unknown, anti-HDL were associated with altered lipid profile, decreased paraoxonase 1 (PON1) activity and CV disease in...

Objectives: Since lipid compounds are known to modulate the function of CD4+ T-cells and macrophages, we hypothesize that altered levels of serum non-esterified fatty acids (NEFA) may underlie rheumatoid arthritis (RA) pathogenesis. Methods: Serum levels of NEFA (palmitic, stearic, palmitoleic, oleic, linoleic, γ-linoleic, arachidonic -AA-, lino...

Chromatograms of serum MTBE-extracted fractions. Total Ion Current chromatograms (TIC) from a representative healthy control (black line) and a RA patient (red line) are shown. Each peak represents a FA as follows: 1 (EPA), 2 (linolenic), 3 (γ-linolenic), 4 (palmitoleic), 5 (DHA), 6 (AA), 7 (linoleic), 8 (palmitic), 9 (oleic), 10 (heptadecanoic) an...

Individual and total NEFA serum levels in RA patients upon TNFα-blockade. Serum levels of individual NEFA (μg/ml, measured by LC-MS/MS) and total NEFA (mM, measured by an enzymatic colorimetric assay) are summarized as median (interquartile range) and differences were analyzed by paired T test. (DOCX)

NEFA and IFNγ serum levels. Analysis of the correlations between serum levels of IFNγ and NEFA species (stearic, EPA and DHA) in RA patients. Correlations were assessed by Spearman rank’s correlation tests, and coefficient correlations and p-values are indicated for each analysis. IFNγ serum levels were log-transformed to facilitate visualization o...

Individual and total NEFA serum levels in RA patients stratified according to disease stages. Serum levels of individual NEFA (μg/ml, measured by LC-MS/MS) and total NEFA (mM, measured by an enzymatic colorimetric assay) are summarized as median (interquartile range) and differences compared with HC were assessed by Mann Withney U test and indicate...

Individual and total NEFA serum levels in RA patients depending on their NEFA profile. Serum levels of individual NEFA (μg/ml, measured by LC-MS/MS) and total NEFA (mM, measured by an enzymatic colorimetric assay) are summarized as median (interquartile range) and differences were assessed by Mann Withney U test. Size effect was evaluated by Hedges...