Erosive Hand Osteoarthritis is Associated with Subclinical Atherosclerosis and Endothelial Dysfunction

Chronic inflammatory disorders have been associated with accelerated atherosclerosis and increased cardiovascular (CV) risk. Recent evidence suggests that erosive hand osteoarthritis (EOA) has considerable inflammation; therefore, we examined the presence of subclinical atherosclerosis and endothelial dysfunction in EOA. Twenty-four patients with EOA and 24 age- and sex-matched healthy individuals without clinical OA were included in the study. No subject had a history of CV disease. Intima-media thickness (IMT) and atheromatous plaques in the common carotid and common femoral arteries were measured by Doppler ultrasonography. The endothelium-dependent, flow-mediated dilatation (FMD) and endothelium-independent, sublingual glyceryl trinitrate (NTG)-induced dilatation (NMD) of the brachial artery were assessed. The EOA patients had significantly elevated systolic and diastolic blood pressure (p\u3c0.001 for both). The 10-year risk of general CV disease, as predicted with the Framingham Risk Score, was similar in patients and controls (p=0.18). IMT of both common carotid and common femoral artery were increased in EOA (p=0.01 and p\u3c0.01, respectively), but the frequency of atherosclerotic plaques was not increased. There was no difference in FMD and NMD between the two groups, but the difference between FMD and NMD was increased in EOA. In conclusion, this small controlled study showed an association between EOA and subclinical atherosclerosis that cannot be fully attributed to traditional CV risk factors, as assessed by the Framingham score. These results suggest that chronic, low-grade inflammation is implicated in atherosclerosis in EOA

Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic Sclerosis

Epitope mapping of anti-Ro52 antibodies (Abs) has been extensively studied in patients with Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). Comprehensive epitope mapping in systemic sclerosis (SSc), where anti-Ro52 antibodies are also frequently detected, has not been performed. The aim of the present study was to fully characterize Ro52 epitopes in anti-Ro52-positive SSc using Ro52 fragments spanning the full antigen. Further analysis was made according to anti-Ro60 status. Epitope mapping was performed in 43 anti-Ro52-positive SSc patients. Seventy eight anti-Ro52-positive pathological controls, including 20 patients with SjS, 28 patients with SLE, 15 patients with dermatomyositis (DM), and 15 patients with primary biliary cholangitis (PBC), and 20 anti-Ro52-negative healthy individuals as normal controls were also tested. Five recombinant Ro52 fragments [Ro52-1 (aa 1-127), Ro52-2 (aa 125-268), Ro52-3 (aa 268-475), Ro52-4 (aa 57-180), and Ro52-5 (aa 181-320) were used to test reactivity by line-immunoassay and in house ELISA. Anti-Ro60 reactivity was tested by ELISA. All anti-Ro52 positive sera reacted with Ro52-2; none recognized Ro52-3. Antibodies against Ro52-1 were less frequently found in SSc than in SjS/SLE (11.6 vs. 41.7%, p = 0.001); and antibodies against Ro52-4 were less frequently found in SSc than in SjS/SLE (27.9 vs. 50%, p = 0.03). In SSc patients, reactivity against Ro52-1 was more frequent in anti-Ro52+/anti-Ro60+ than in anti-Ro52+/anti-Ro60-patients (33.3 vs. 0%, p = 0.003). In this comprehensive analysis of Ro52 epitope mapping in SSc, the coiled coil domain remains the predominant epitope on Ro52. Contrary to SjS and SLE, patients with SSc fail to identify epitopic regions within the N-terminus of the protein, especially if they lack con-current anti-Ro60 reactivity

Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis

<p>Abstract</p> <p>Background</p> <p>The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis.</p> <p>Methods</p> <p>Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography.</p> <p>Results</p> <p>Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and D_LCOwere independent predictors of systolic pulmonary artery pressure.</p> <p>Conclusion</p> <p>Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.</p

Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek patients with rheumatoid arthritis

Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis ( RA). In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients. Methods: Using an enzyme-linked immunosorbent assay ( ELISA) (CCP2) kit, we tested anti-CCP antibodies in serum samples from 155 Greek patients with RA, 178 patients with other rheumatic diseases, and 100 blood donors. We also determined rheumatoid factor (RF) and compared it to anti-CCP antibodies for area under the curve (AUC), sensitivity, specificity and likelihood ratios. Results: Sensitivity of anti-CCP2 antibodies and RF for RA was 63.2% and 59.1%, and specificity was 95.0% and 91.2%, respectively. When considered simultaneously, the AUC for anti-CCP antibodies was 0.90 with 95% CI of 0.87 to 0.93 and the AUC for RF was 0.71 with 95% CI of 0.64 to 0.77. The presence of both antibodies increased specificity to 98.2%. Anti-CCP antibodies were positive in 34.9% of RF-negative RA patients. Anti-CCP antibodies showed a correlation with the radiographic joint damage. Anti-CCP-positive RA patients had increased the swollen joint count and serum CRP concentration compared to anti-CCP-negative RA patients (Mann-Whitney U test, p = 0.01, and p < 0.001, respectively). However, no correlation was found between anti-CCP antibodies and DAS28 score ( r = 0.13, p = 0.12). Conclusion: In Greek patients with RA, anti-CCP2 antibodies exhibit a better diagnostic value than RF and a correlation with radiological joint damage and therefore are useful in everyday rheumatology practice

The prevalence of rheumatic diseases in central Greece: a population survey

<p>Abstract</p> <p>Background</p> <p>Rheumatic diseases are a major health and financial burden for societies. The prevalence of rheumatic diseases may change over time, and therefore, we sought to estimate the prevalence of rheumatic diseases in an adult population of central Greece.</p> <p>Methods</p> <p>In this prospective cross-sectional population survey, a random sample of adult population was drawn from poll catalogues of a region in central Greece. A postal questionnaire was sent to 3,528 people for the presence of any rheumatic disease. All positive cases were further confirmed by clinical examination using the American College of Rheumatoloy criteria. Multiple regression analysis was used to assess risk factors for rheumatic diseases.</p> <p>Results</p> <p>The response rate was 48.3% (1,705 answers). Four hundred and twenty individuals (24.6%) had a rheumatic disease. The prevalence of rheumatoid arthritis was 0.58% (95% confidence interval [CI], 0.32-0.87), of psoriatic arthritis was 0.35% (95% CI, 0.33-1.13), of ankylosing spondylitis was 0.29% (95% CI, 0.28-0.94), of primary Sjögren's syndrome was 0.23% (95% CI, 0.22-0.75) and of systemic lupus erythematosus was 0.11% (95% CI, 0.11-0.37). One individual had systemic sclerosis (prevalence, 0.058%), 1 individual had dermatomyositis (prevalence, 0.058%; 95% CI, 0.05-0.18), 2 individuals had vasculitis (prevalence 0.11%; 95% CI, 0.11-0.37), 81 individuals had gout (prevalence, 4.75%; 95% CI, 4.41-5.13), and 304 individuals had osteoarthritis (OA) (prevalence 17.82%; 95% CI, 16.50-19.34). Gout was associated with male gender, diabetes mellitus, and hypertension, and OA was associated with age, female gender, and hypertension.</p> <p>Conclusions</p> <p>Rheumatic diseases are common in central Greece, affecting nearly a quarter of adult population. OA and gout are the most common joint disorders.</p

New Developments in the Pathogenesis of Rheumatoid Arthritis

The pathogenesis of rheumatoid arthritis (RA) is incompletely understood. HLA class II alleles and T cells have been implicated for many years. The discovery of anticitrullinated peptide antibodies (ACPAs), along with the effectiveness of biological treatments targeting cytokines, such as TNF-?, IL-6, and also T cells and B cells, reinforced the pathogenetic role of the respective factors. ACPAs, induced by cigarette smoking and periodontitis in individuals with HLA-DRB1 shared epitope, appear to be autoantigens that initiate the inflammatory immune response in RA. MicroRNAs, part of epigenetic mechanisms, which also include DNA methylation, and histone modification, as well as microbiota, the composition of microbes in body cavities, also appear to influence arthritis and are discussed in this book

The Role of T Cells in Systemic Sclerosis: An Update

Systemic sclerosis (SSc) is a chronic disease characterized by microvasculopathy, autoantibodies (autoAbs), and fibrosis. The pathogenesis of the disease is incompletely understood. Microvasculopathy and autoAbs appear very early in the disease process. AutoAbs, such as those directed against DNA topoisomerase I (Topo I), are disease specific and associated with disease manifestations, and indicate activation of the adaptive immune system. B cells are involved in fibrosis in SSc. T cells are also involved in disease pathogenesis. T cells show signs of antigen-induced activation; T cells of TH2 type are increased and produce profibrotic cytokines interleukin (IL)-4, IL-13, and IL-31; CD4+ cytotoxic T lymphocytes are increased in skin lesions, and cause fibrosis and endothelial cell apoptosis; circulating T follicular helper (TFH) cells are increased in SSc produce IL-21 and promote plasmablast antibody production. On the other hand, regulatory T cells are impaired in SSc. These findings provide strong circumstantial evidence for T cell implication in SSc pathogenesis and encourage new T cell-directed therapeutic strategies for the disease