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Objective: Endothelial dysfunction has been associated with increased cardiovascular events and overall mortality. Microvascular damage is prevalent both in diabetes mellitus (DM) and chronic kidney disease (CKD). Our aim was to compare microcirculatory function parameters in diabetic and non‐diabetic CKD patients via nailfold video‐capillaroscopy. Methods: We included 48 diabetic and 48 non‐diabetic adult CKD patients. All participants underwent nailfold video‐capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4‐minute arterial occlusion (postocclusive reactive hyperemia), and at the end of a 2‐minute venous occlusion (congestion phase). Results: Diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3 ± 3.8 vs 38.3 ± 4.3 capillaries/mm2, P =.022) and at venous congestion (37.8 ± 4.0 vs 39.8 ± 4.2 capillaries/mm2, P =.015). When stratified according to CKD stages, only in stage 3b capillary density was significantly lower in diabetic compared to non‐diabetic subjects at baseline, during postocclusive hyperemia (36.8 ± 2.7 vs 40.0 ± 4.3 capillaries/mm2, P =.037) and venous congestion (38.3 ± 2.8 vs 41.5 ± 3.5 capillaries/mm2, P =.022). Conclusions: Capillary density during postocclusive hyperemia and after venous congestion is lower in diabetic compared to non‐diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory structural and functional impairment in CKD. These differences are more prominent in CKD stage 3b. [ABSTRACT FROM AUTHOR]

Objectives Evidence on comorbidity prevalence in antiphospholipid syndrome (APS) and its difference from high comorbidity burden rheumatic diseases is limited. Herein, we compare multiple comorbidities between APS and RA. Methods A total of 326 patients from the Greek APS registry [237 women, mean age 48.7 (13.4) years, 161 primary APS (PAPS), 165 SLE-APS] were age/sex matched (1:2 ratio) with 652 patients from a Greek multicentre RA cohort of 3115 patients. Prevalence of cardiovascular (CV) risk factors, stroke, coronary artery disease (CAD), osteoporosis, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), depression and neoplasms were compared between APS and RA patients using multivariate regression analysis. Results Ηyperlipidemia and obesity (ΒΜΙ ≥ 30 kg/m2) were comparable while hypertension, smoking, stroke and CAD were more prevalent in APS compared with RA patients. Osteoporosis and depression were more frequent in APS, while DM, COPD and neoplasms did not differ between the two groups. Comparison of APS subgroups to 1:2 matched RA patients revealed that smoking and stroke were more prevalent in both PAPS and SLE-APS vs RA. Hypertension, CAD and osteoporosis were more frequent only in SLE-APS vs RA, whereas DM was less prevalent in PAPS vs RA. Hyperlipidaemia was independently associated with CV events (combined stroke and CAD) in PAPS and SLE-APS, while CS duration was associated with osteoporosis in SLE-APS. Conclusion Comorbidity burden in APS (PAPS and SLE-APS) is comparable or higher than that in RA, entailing a high level of diligence for CV risk prevention, awareness for depression and CS exposure minimization. [ABSTRACT FROM AUTHOR]

COVID-19 vaccination can occasionally trigger autoimmune phenomena, probably via inducing age-associated B cells Keywords: age-associated B cells; autoimmune rheumatic diseases; coronavirus disease 2019; vaccination EN age-associated B cells autoimmune rheumatic diseases coronavirus disease 2019 vaccination 83 85 3 01/05/22 20220101 NES 220101 AGE-ASSOCIATED B CELLS Age-associated B cells (ABCs) constitute a CD11c SP + sp T-bet SP + sp B-cell population that expands continuously with age in healthy individuals,1 but also displays a premature accumulation in cases of autoimmune and/or infectious diseases.2-5 In autoimmune settings, ABCs are implicated in the production of autoreactive immunoglobulin G,2 the enhanced antigen presentation to T cells, and the formation of spontaneous germinal centers.6,7 T-bet, which is a transcription factor highly expressed in ABCs, is considered to be the master regulator of all these processes,8 although new data suggest that its expression may not be required for the generation of functional ABCs.9 In humans, the ABC subset is also known as double-negative (DN) B cells because of the lack of immunoglobulin D and CD27 memory marker expression.10-12 DN B cells have been further divided into two subgroups, based on the expression of the follicular homing marker CXCR5.13 More specifically, the CXCR5 SP + sp cells (DN1) are expanded in elderly healthy individuals and lack T-bet expression, whereas the CXCR5 SP - sp cells (DN2) express T-bet and are more marked in autoimmune diseases (mostly systemic lupus erythematosus).10,11,13 The DN2 cells are hyper-responsive to Toll-like receptor 7 (TLR7) signaling, so are poised to generate autoreactive antibody-secreting plasmablasts.13 In general though, their role in the development of autoimmunity remains elusive. Age-associated B cells, autoimmune rheumatic diseases, coronavirus disease 2019, vaccination. [Extracted from the article]

Juvenile idiopathic arthritis (JIA) is an autoimmune disease that is characterized by persistent chronic arthritis and affected by genetic and environmental factors. Different genetic variations have been reported as risk factors for JIA. However, given that many results could not be replicated in individuals of different ancestral origin, it was assumed that heterogeneous genetic factors are involved in this disease. In the present study, we analyzed three single nucleotide polymorphisms (SNPs), namely PTPRC (rs10919563), TYK2 (rs34536443) and PRKCQ (rs4750316), which were found to be associated with JIA in previous studies. We also investigated whether the intron-4 located 27-bp VNTR of endothelial nitric oxide synthase (eNOS), is associated with risk for JIA in Greece. In total, 125 JIA patients and 221 healthy controls from northern Greece were included in the study as a sample set. Samples were then analyzed, and genotyped for the three SNPs with TaqMan primer-probe sets, using a Real-Time PCR platform (ViiA™ 7 Real-Time PCR system), while eNOS VNTR polymorphism was genotyped by PCR. Statistical analysis was performed using a GraphPad Prism statistical program. The χ² test was used to examine differences of genotype and allele frequencies between patients and controls. Statistical significance was defined by using the two-tailed P<0.05 test. Bioinformatics analysis was conducted by using BlastP, Pymol, Maestro and Desmond. In the case-control association study performed, eNOS only was found to be associated with JIA. Genotype a/a and allele 'a' were found in a higher frequency in JIA patients than in controls [p<0.0001, odds ratio (OR)=0.15, 95% confidence intervals (CI): 0.065-0.37; and p<0.0001, OR=0.34, 95% CI: 0.23-0.49, respectively]. No associations with JIA were detected for TYK2, PTPRC or PRKCQ. Aiming to investigate the structural consequences and the structure/function relationships accompanying the Pro1104 to Ala (rs34536443) mutation on TYK2 protein, bioinformatics analysis was performed. Combining three-dimensional (3D)-modeling and molecular dynamics simulations we identified changes in structural flexibility, affecting the functionality of the kinase domain of TYK2. To the best of our knowledge, this is the first time that eNOS VNTR polymorphism is associated with susceptibility to JIA, suggesting a differential role of allele 'a' in various complex diseases. The current data emphasize the importance of comparative studies in populations of a different ancestral background towards the clarification of the role of specific alleles in the development of JIA. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of multiple organs (kidney, heart, lung, gastrointestinal tract, and skin), endothelial damage leading to vascular disease, and autoantibody production. Although the microvascular disease is well-understood, mechanistic insights explaining the presence and extent of macrovascular disease in SSc patients has been a matter of intense debate, especially in the past few years. Patients with systemic sclerosis have an increased risk for atherosclerotic cardiovascular disease (CVD), possibly mediated by inflammatory and fibrotic mechanisms. The excess cardiovascular risk in SSc is suggested by increased arterial stiffness, carotid intima thickening, and reduced flow-mediated dilatation. Given the involvement of the microvasculature, the differentiation between primary and ischemic heart disease is difficult. There is a relative paucity of data regarding clinical and preclinical CVD in SSc. Therefore, large cohort studies are required to clarify whether CVD is predominantly associated with atherosclerosis or microvascular involvement. The aim of this review is to discuss primary and ischemic heart disease and their contribution to CVD in SSc. [ABSTRACT FROM AUTHOR]

Background: Age-associated B cells (ABCs) constitute a B cell subset, defined as CD19 + CD21 - CD11c + , that expands continuously with age and accumulates strongly in individuals with autoimmune and/or infectious diseases. In humans, ABCs are principally IgD - CD27 - double-negative (DN) B cells. Data from murine models of autoimmunity, implicate ABCs/DN in the development of autoimmune disorders. T-bet, a transcription factor which is highly expressed in these cells, is considered to play a major role in various aspects of autoimmunity, such as the production of autoantibodies and the formation of spontaneous germinal centres., Aims of the Study: Despite the available data, the functional features of ABCs/DN and their exact role in the pathogenesis of autoimmunity remain elusive. This project focuses on the investigation of the role of ABCs/DN in the pathogenesis of systemic lupus erythematosus (SLE) in humans, as well as the effects that various pharmacological agents may have on these cells., Methods: Samples from patients with active SLE will be used to enumerate and immunophenotype - via flow cytometry - the ABCs/DN found in the peripheral blood of the patients. Transcriptomic analysis and functional assays for the cells, both before and after in vitro pharmacological treatments, will also be performed., Anticipated Benefits: The results of the study are expected to allow characterization of the pathogenetic role of ABCs/DN in SLE and could probably contribute, following careful association with the clinical state of the patients, towards the discovery and validation of novel prognostic and diagnostic markers of disease., Competing Interests: The authors declare no conflict of interest., (© 2023 The Mediterranean Journal of Rheumatology (MJR).)