Chronic Inflammatory Rheumatic Disorders Research Articles

Recommendations for assessing the risk of cardiovascular disease and venous thromboembolism before the initiation of targeted therapies for chronic inflammatory rheumatic diseases.

Patients with rheumatoid arthritis (RA) and other chronic inflammatory rheumatic disorders have increased risk of cardiovascular disease (CVD) and venous thromboembolism (VTE) compared with the general population. Moreover, recent data have raised concerns around a possible increased risk of major CV events (MACE) and VTE in patients treated with JAK inhibitors (JAKi). In October 2022, the PRAC has recommended measures to minimize the risk of serious side effects, including CV conditions and VTE, associated with all approved in chronic inflammatory diseases. To provide an adequate and feasible strategy to evaluate, at the individual level, the risk of CVD and VTE in patients with chronic inflammatory rheumatic diseases. A multidisciplinary steering committee comprised 11 members including rheumatologists, a cardiologist, a hematologist expert in thrombophilia and fellows. Systematic literature searches were performed and evidence was categorized according to standard guidelines. The evidence was discussed and summarized by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk of MACE and VTE in patients with chronic inflammatory rheumatic diseases compared with the general population. Second, the rheumatologist has a central role in the evaluation of the risk of CVD and VTE in patient with chronic inflammatory rheumatic diseases. Third, the risk of MACE and VTE should be regularly assessed in patients with chronic inflammatory rheumatic diseases, particularly before initiating targeted therapies. Eleven recommendations were defined to prevent potentially life-threatening complications of CVD and VTE in patients with chronic inflammatory rheumatic diseases, providing practical assessment of CVD and VTE before considering the prescription of targeted therapies, and especially JAKi. These practical recommendations based on expert opinion and scientific evidence provide consensus for the prevention and the assessment of CVD and VTE.

Analytical and clinical evaluation of DiaSorin Liaison® Calprotectin fecal assay adapted for serum samples.

BackgroundCalprotectin is a calcium‐binding protein that can be measured in serum, plasma, and feces. Increased serum and plasma calprotectin concentrations have been found in chronic inflammatory rheumatic disorders. An analytical and clinical evaluation of the DiaSorin Liaison® fecal Calprotectin assay using LIAISON® XL was performed.MethodsThe protocol included an analytical and clinical evaluation in which imprecision, the linearity of dilution, differences between serum and plasma samples and method comparison with CalproLab™ ELISA kit were assessed. Serum calprotectin concentrations in active (n = 26) and remission (n = 23) rheumatoid arthritis (RA) patients were compared.ResultsThe intra‐day and inter‐day analytical imprecision CVs ranged from 2.9% to 4.0% and 2.7% to 10.4%, respectively. Correlation between measured and expected values was high (R > 0.99), indicating good linearity. The Wilcoxon signed‐rank test showed that serum and plasma matched samples presented statistically significant differences (p < 0.001) being the highest concentrations of calprotectin observed in serum samples. Deming regression equation was as follows: Diasorin calprotectin (μg/ml) = −0.32 (95% CI: −0.65 ‐ −0.05) +1.58 (95% CI: 1.42–1.79).* Calprolab calprotectin (μg/ml). Significantly higher serum calprotectin levels were found in RA patients with active disease when compared to patients with low disease activity or in clinical remission (mean ± SD) [(3.35 μg/ml ± 1.55) vs. (1.63 μg/ml ± 0.52), p < 0.001] and these levels correlated well with all disease activity indices.ConclusionsThe DiaSorin Liaison® fecal Calprotectin assay adapted for serum samples showed adequate technical performances and the clinical performances were similar to other assays.

Ankylosing Spondylitis: A Risk Factor for Parkinsonism-A Nationwide Population-Based Study.

Ankylosing spondylitis (AS) is an immune-mediated, chronic inflammatory rheumatic disorder. The etiology of Parkinson's disease (PD) is multifactorial; however, inflammation is receiving an increasing amount of attention as an underlying cause of the neurodegenerative process of PD. We performed a nationwide longitudinal, population-based matched cohort study to assess the association with the later development of parkinsonism in Korea. This study was conducted using records from the Health Insurance Review and Assessment Service database. The cumulative incidence rate of PD was estimated. Fine-Gray subdistribution hazard models were used to identify hazards associated with PD development based on the presence of AS. Exposure to anti-inflammatory drugs was measured and analyzed to determine the protective effect of these medications. Additionally, the hazard ratio (HR) for atypical parkinsonism was estimated. The results of the Fine-Gray subdistribution hazard model revealed that the HR for PD development in the AS group was 1.82 (95%confidence interval [CI], 1.38-2.39, p < 0.001). A significant decrease in PD development was observed in patients with AS taking non-steroidal anti-inflammatory drugs (NSAIDs). The HR for atypical parkinsonism in the AS group was 3.86 (95%CI, 1.08-13.78, p < 0.05). We found that AS was associated with an increased risk of PD and atypical parkinsonism. NSAIDs used for AS control have some protective effects against PD. Further studies assessing whether biological treatment mitigates PD risk in patients with high activity are warranted.

Immunogenicity of Rituximab biosimilar GP2013 in chronic inflammatory rheumatic disorders in daily clinical practice

ObjectiveTo study in daily practice the risk of immunogenicity of patients treated with the biosimilar rituximab (RTX) GP2013 used for chronic inflammatory rheumatic disorders. MethodsA prospective monocentric routine care study was carried out between September 2018 and May 2021, including consecutive patients treated with the biosimilar RTX GP2013. Biosamples were taken before each infusion to quantify anti-RTX antibodies (ADAbs) and serum RTX trough levels by ELISA (Lisa Tracker Duo Rituximab, LTR005, Theradiag). Results168 GP2013-treated patients were included (129 who switched from originator RTX and 39 originator RTX naïve). The analysis of 602 samples identified 15 patients (8%) with positive ADAbs including 6 and 9 with transient and persistent ADAbs, respectively. The switch from originator RTX to GP2013 did not increase the risk of immunogenicity, with an incidence rate of 0.8 for 100 patient years. The frequency of persistent ADAs was higher in non-RA patients (5/56, 9% vs. 4/112, 3.5%). Patients with positive persistent ADAbs were more frequently non-caucasian (7/9, 78%, vs. 56/159, 35%, p<0.01) and all had detectable circulating B cells (vs. 40% in ADAb-negative patients, P<0.001). ADAb positivity was not associated with disease activity or RTX discontinuation but patients with ADAb titers >100 ng/mL experienced reduced treatment efficacy or severe infusion-related reaction. ConclusionWithin the study duration, the immunogenicity of GP2013 is a rare event affecting the pharmacodynamics of RTX. Although development of ADAbs had no impact on treatment discontinuation, possible harmful consequences may be observed in patients with high antibody levels.

Functionally Active Antibodies to the Angiotensin II Type 1-Receptor Measured by a Luminometric Bioassay Do Not Correlate With Clinical Manifestations in Systemic Sclerosis: A Comparison With Antibodies to Vascular Receptors and Topoisomerase I Detected by ELISA.

Objectives1) To detect functionally active antibodies(abs) to the angiotensin II type-1-receptor (AT1R) by a novel luminometric assay. 2) To assess their prevalence in systemic sclerosis (SSc), other collagen disorders, as well as in further chronic inflammatory disorders including autoimmune, toxic and chronic viral diseases. 3) To compare these abs with anti-AT1R antibodies by ELISA as well as with antibodies to endothelin-type-A receptors (ETA1) and to topoisomerase I (topo-I) with respect to their specificity and clinical relevance.MethodsSera from 98 SSc-patients, 110 patients with other chronic inflammatory rheumatic disorders, 97 patients with autoimmune liver diseases, 57 patients with toxic or chronic viral liver diseases and 36 healthy controls were analyzed. A luminometric bioassay was established with Huh-7-cells constitutively expressing the AT1R. Patients’ sera were also tested by commercially available ELISA for anti-AT1R, -ETA1- and by an in-house ELISA for anti–topo-I-abs.ResultsFifty-two percent of the SSc-patients had functionally active anti-AT1R-abs with stimulatory (34%) or inhibitory capacity (18%). They were present also in up to 59% of patients with other rheumatic diseases but only 22% of healthy individuals (sensitivity 52%, specificity 53%). The functionally active antibodies detected by the luminometric assay did not correlate with anti-AT1R-, -ETA1- or -topo-I-abs measured by ELISA, but there was a strong correlation between anti-topo-I-, AT1R-, and -ETA1-ab reactivity measured by ELISA. Sensitivities of 55%, 28% and 47% and specificities of 66%, 87%, and 99% were calculated for these anti-AT1R-, -ETA1-, and anti-topo-I-abs, respectively. Functionally active abs did not correlate with disease severity or any organ manifestation. In contrast, abs to topo-I, AT1R, and ETA1 were associated with digital ulcers, pulmonary- and esophageal manifestation.ConclusionsFunctionally active anti-AT1R-abs can be detected in SSc-patients but do not correlate with disease activity. They are not specific for this disease and occur also in other autoimmune disorders and even viral or toxic diseases. Also, the vascular antibodies detected by ELISA are not SSc-specific but correlated with disease manifestations. In contrast, anti-topo-I-abs were confirmed to be a highly specific biomarker for both, diagnosis and organ manifestations of SSc.

Infections ostéoarticulaires et traitements ciblés des rhumatismes inflammatoires

Patients with chronic inflammatory rheumatic disorders may present an increased risk of osteoarticular infection related to age, comorbidities, previous intra-articular corticosteroid injection, surgical procedures or the use of immunosuppressive drugs including corticosteroids or targeted therapies. Data regarding the risk of osteoarticular infection remain scarce and mainly restricted to TNF-α inhibitors. Although an increased risk of osteoarticular infection in native or prosthetic joints of patients receiving targeted biological therapies has been reported in various national and international registries, it appears to be moderate, lower than respiratory, skin, and urinary infections. The risk of osteoarticular infection also remains stable over time, similar to what was described before the era of biologic therapies. Moreover, this risk must be balanced against that of corticosteroids, which are often necessary to control flare-ups induced by the suspension of the biological agent. Staphylococcus aureus remains the most frequently observed microorganism, but certain species usually barely involved in osteoarticular infections should be assessed in these patients. Osteoarticular infection in patients receiving targeted therapies should not be ruled out in absence of fever and/or elevation of acute phase reactants. Several questions need to be addressed, including the weight of targeted therapies in the increased risk of osteoarticular infection compared to other risk factors, in particular age, the underlying rheumatic disease or corticosteroid therapy.

The pathogenic role of coronary microvascular dysfunction in the setting of other cardiac or systemic conditions.

Coronary microvascular dysfunction (CMD) plays a pathogenic role in cardiac and systemic conditions other than microvascular angina. In this review, we provide an overview of the pathogenic role of CMD in the setting of diabetes mellitus, obesity, hypertensive pregnancy disorders, chronic inflammatory and autoimmune rheumatic disorders, chronic kidney disease, hypertrophic cardiomyopathy, and aortic valve stenosis. In these various conditions, CMD results from different structural, functional, and/or dynamic alterations in the coronary microcirculation associated with the primary disease process. CMD is often detectable very early in the course of the primary disease, before clinical symptoms or signs of myocardial ischaemia are present, and it portrays an increased risk for cardiovascular events.

Recommendations for the assessment and optimization of adherence to disease-modifying drugs in chronic inflammatory rheumatic diseases: A process based on literature reviews and expert consensus.

Adherence to treatment is a key issue in chronic inflammatory rheumatic diseases (CIRDs). To develop recommendations to facilitate in daily practice, the management of non-adherence to disease-modifying drugs in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, connective tissue diseases or other CIRDs. The process comprised (a) systematic literature reviews of methods (including questionnaires) to measure non-adherence, risk factors for non-adherence and efficacy of targeted interventions; (b) development of recommendations through consensus of 104 rheumatologist and nurse experts; (c) assessment of agreement and ease of applicability (1-5 where 5 is highest) by the 104 experts. (a) Overall, 274 publications were analysed. (b) The consensus process led to 5 overarching principles and 10 recommendations regarding adherence. Key points include that adherence should be assessed at each outpatient visit, at least using an open question; questionnaires and hydroxychloroquine blood level assessments may also be useful. Risk factors associated to non-adherence were listed. Patient information and education, and patient/physician shared decision, are key to optimize adherence. Other techniques such as formalized education sessions, motivational interviewing and cognitive behavioral therapy may be useful. All health professionals can get involved and e-health may be a support. (c) The agreement with the recommendations was high (range of means, 3.9-4.5) but ease of applicability was lower (2.7-4.4). Using an evidence-based approach followed by expert consensus, this initiative should improve the assessment and optimization of adherence in chronic inflammatory rheumatic disorders.

Methods to improve medication adherence in patients with chronic inflammatory rheumatic diseases: a systematic literature review

ObjectiveLack of adherence to treatment is frequent in chronic inflammatory rheumatic diseases and is associated with poorer outcomes. The objective of this study was to describe and evaluate interventions that...

Immuno-biological Assessments of Temporomandibular Joint Disease in Patients with Immune-mediated Rheumatic Conditions. A cross sectional study of 273 cases

Temporomandibular joint (TMJ) is commonly involved in various immune-mediated rheumatic disorders accounting for significant disability and impaired quality of life. The aim of our study was to assess inflammatory and immune parameters in patients with TMJ arthritis related to rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to identify potential relation with severity and dysfunction of TMJ pathology. We performed a cross-sectional study in a cohort of 433 consecutive RA, 32 JIA, 258 AS, and 103 PsA. Only patients presenting with clinically significant TMJ involvement (273) related to their rheumatic condition were included in the final analysis. TMJ involvement is traditionally described in chronic inflammatory rheumatic disorders, particularly in patients with higher levels of inflammation as detected in rheumatoid arthritis and psoriatic arthritis. Disease activity and severity, as well as biological and positive serological assessments (rheumatoid factor, anti-cyclic citrullinated peptide, IL-1) remain significant determinants of the severity of TMJ arthritis.

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion

Reversal of Arthritis by Human Monomeric IgA Through the Receptor-Mediated SH2 Domain-Containing Phosphatase 1 Inhibitory Pathway.

Rheumatoid arthritis (RA), one of the most frequent chronic inflammatory rheumatic disorders, is characterized by the presence of autoantibodies and joint infiltration by activated immune cells, leading to cartilage and bone destruction. IgA occurs predominantly as monomers (mIgA) in plasma and regulates many cell responses through interaction with the Fcα receptor type I (FcαRI). FcαRI targeting by anti-FcαRI Fab inhibits activating receptors by inducing an inhibitory immunoreceptor tyrosine-based activation motif (ITAMi) configuration through SH2 domain-containing phosphatase 1 (SHP-1) recruitment. The aim of this study was to investigate the potential utility of mIgA for the treatment of arthritis by acting as an inducer of ITAMi signaling. The effect of plasma-derived human mIgA on inhibition of multiple heterologous receptors was evaluated on FcαRI+ cell transfectants, blood phagocytes from healthy individuals, and synovial cells from RA patients. FcαRI-transgenic mice and wild-type mice treated with mIgA were studied in models of collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA). The mice were assessed for development of arthritis using an arthritis score, and joint tissue samples were evaluated for the extent of leukocyte infiltration and expression of phosphatase. Treatment with mIgA impaired cell activation in an FcαRI-FcRγ-dependent manner, involving ITAMi signaling. Human mIgA or anti-FcαRI Fab were strongly effective in either preventing or attenuating CAIA or CIA in FcαRI-transgenic mice. Administration of mIgA markedly inhibited the recruitment of leukocytes to the inflamed joints of mice, which was associated with induction of SHP-1 phosphorylation in joint tissue cells. Moreover, mIgA reversed the state of inflammation in the synovial fluid of RA patients by inducing an ITAMi configuration. These results demonstrate a therapeutic potential of human mIgA in experimental arthritis. The findings support future clinical exploration of mIgA for the treatment of RA.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis

Objectives. Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation.Methods. Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups.Results. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values <0.001). cTp-e interval and Tp-e/QT ratio were significantly correlated with hsCRP (r = 0.63, P < 0.001 and r = 0.49, P < 0.001, respectively).Conclusions. Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. METHODS: Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. RESULTS: In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7±9.6 vs 28.2±7.4 and 35.8±11.5 vs 30.6±7.9ms, P=0.03 and P=0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1±10.2 vs 75.8±8.4 and 0.22±0.02 vs 0.19±0.02ms, all P values <0.001). cTp-e interval and Tp-e/QT ratio were significantly correlated with hsCRP (r=0.63, P<0.001 and r=0.49, P<0.001, respectively). CONCLUSIONS: Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

English

Introduction Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disorder with unclear pathogenesis. Bone formation is a hallmark feature of AS, precise mechanisms of which are unknown. The aim of this review was to summarize the current knowledge regarding both clinical significance and pathogenesis of bone formation in AS. Materials and methods Articles, published in the medical literature and chapters in textbooks related to the discussed topic, were critically reviewed and relevant data were selected, collated and organized for the purpose of this manuscript. Results Conventional radiography is the most valuable classical tool for identification of structural changes in AS. The typical manifestations of bone formation in AS usually involve the axial skeleton, including spine, sacroiliac and hip joints, and, if properly recognized, have an important role in diagnosing, classifying and monitoring patients. Molecular pathways leading to bone formation in AS have not been elucidated sufficiently. Abnormally active signalling by wingless-type (wnt)-like and bone morphogenic protein (BMP)-mediated pathways have been suggested as major contributors to diseaserelated ossification in AS. The only medicines, shown currently to delay the process of bone formation in AS patients, are nonsteroidal anti-inflammatory drugs. Conclusion Better understanding and prediction of structural damage would help to improve and individualize management of patients suffering from AS.

Ankylosing Spondylitis and Cardiac Abnormalities

REFER TO THE PAGE 30-36 There are a number of systemic diseases with cardiovascular manifestations in which echocardiography plays a valuable role for surveillance and follow-up of anticipated cardiovascular abnormalities. Systemic autoimmune disorders are frequently associated to cardiac involvement such as pericarditis, myocarditis, valvular abnormalities or ischemic coronary disease. Ankylosing spondylitis (AS) is also a chronic systemic inflammatory rheumatic disorder that primarily affects the axial joints and mainly involves young male. Extra-articular manifestations vary widely in terms of both frequency and severity. The most common extra-articular manifestations are uveitis, bowel disease, skin, lung and kidney involvement; less frequently cardiovascular involvement occurs.1) Screening for extra-articular manifestations in patients with AS is important for appropriate management as the presence of extra-articular manifestations may be a consequence of uncontrolled systemic inflammation and may influence treatment decisions.2) The prevalence of cardiac pathologies in patients with AS has been reported to be 10% to 30%.3) It is related to a sclerosing inflammatory process that primarily involves the aortic root and the aortic valve, and the chronic inflammation may extend into the ventricular septum, atrioventricular node, proximal bundle of His and bundle branches or fascicles. Thus, various studies indicate a higher rate of conduction disturbances, valvular heart disease and ascending aortic involvement in patients with AS compared with the normal population.4) In this issue of the journal, Park et al.5) reported the early valvular and aortic involvement in young male patients with AS using transesophageal echocardiography. A total of 70 AS patients were divided into AS group I (< 10 years of disease duration) and AS group II (≥ 10 years) depending on their disease duration after the first diagnosis. The thickness of aortic valve was increased in AS patients than in control (control vs. AS group I vs. AS group II, 1.2 ± 0.3 vs. 1.8 ± 0.7 vs. 2.1 ± 0.8 mm, p < 0.01). The thickness of mitral valve was also increased in AS patients (control vs. AS group I vs. AS group II, 0.9 ± 0.1 vs. 1.2 ± 0.3 vs. 1.2 ± 0.4 mm, p < 0.01). Aortic root diameter at the sinus of Valsalva was slightly increased in AS group II. Furthermore, aortic strain and distensibility were decreased and aortic stiffness beta index was increased in AS group II compared with control and AS group I. Mitral annulus early diastolic velocity (E') and systolic velocity (S') by tissue Doppler imaging were slightly decreased in AS group II. However there was no increased rate for valvular regurgitation (aortic and mitral valve) and for conduction disturbances. There are some limitations in this study. As they described, the design of this study was observational and cross-sectional, and conducted in a single center. The clinical significance of the results is unclear in this design. Thus a large long-term prospective study is needed to elucidate the clinical significance of early changes in valve, aorta and myocardial function. There was no age-matched control group for AS group II. Mean ages of both control and AS group I were 27 years. However mean age of AS group II was 34 years. Thus it is unclear whether the slight differences in parameters of tissue Doppler and aortic stiffness were from difference of disease duration or from difference of age. Finally the effects of disease activities and drug therapy for AS on cardiac and aortic abnormalities were not fully evaluated in this study. Despite the limitations, Park et al's study5) give us useful informations about early subclinical changes of aorto-mitral valve and aortic stiffness in AS patients in the era of advanced management of AS with immunosuppressive and/or immune-modulating drugs.

Pharmacologic P2X purinergic receptor antagonism in the treatment of collagen‐induced arthritis

To assess the therapeutic potential of a P2X purinergic receptor antagonist, namely, periodate oxidized ATP, in collagen-induced arthritis (CIA). Arthritis was induced in male DBA/1J mice by immunization with type II collagen (CII). Animals showing digit inflammation and paw swelling were treated intraperitoneally with 100 μl of 3 mM oxidized ATP daily for 10 days. At the end of the treatment period, animals were killed and paws were removed for histologic analysis and evaluation of T cell infiltration. Humoral response to CII was analyzed, and specific serum autoantibody levels were correlated with the clinical scores observed in the different treatment groups. Treatment with oxidized ATP resulted in a sustained reduction in disease activity, which was associated with a significant decrease in CD3+ T cell infiltration in arthritic lesions and a significant amelioration of cartilage erosion. Peripheral Treg cells were significantly increased upon P2X blockade in mouse lymph nodes. Moreover, a marked reduction in circulating autoantibodies directed against mouse CII was detected. There was a significant correlation between serum autoantibody levels and the clinical efficacy of oxidized ATP. Our findings indicate that P2X receptor antagonism has important therapeutic potential in chronic inflammatory rheumatic disorders. Taken together, our results underscore the value of the P2X receptor signaling pathway as a potential pharmacologic target for the modulation of adaptive immunity in CIA.

Cardiovascular Risk in Rheumatoid Arthritis and Systemic Autoimmune Rheumatic Disorders: a Suggested Model of Preventive Strategy

The pathogenesis of accelerated cardiovascular damage commonly characterizing patients affected by systemic chronic inflammatory and autoimmune rheumatic disorders is quite complex and still not fully clarified. However, it is well accepted that a strong relationship between multiple factors, including both traditional cardiovascular risk factors and disease-related inflammatory and autoimmune mechanisms, may in part explain the precocious atherosclerotic vessel damage and the increased incidence of cardiovascular events. Nevertheless, although several recent studies focused their attention on the investigation of these complex mechanisms, data regarding possible preventive strategies aimed to reduce long-term cardiovascular risk in these subjects are still lacking and not conclusive. In this setting, the early introduction of evidence-based preventive measures for the correct management of patients with systemic autoimmune disorders would be of extreme importance to reduce subclinical atherosclerosis incidence and possible major cardiovascular events.

Arterial Distensibility in Chronic Inflammatory Rheumatic Disorders

The pulse wave velocity (PWV), as an indicator of arterial distensibility, may play an important role in the stratification of patients based on the cardiovascular risk. PWV inversely correlates with arterial distensibility and relative arterial compliance. Decreased arterial distensibility alters arterial blood pressure and flow dynamics, and disturbes coronary perfusion. Systemic immune and inflammatory diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with increased morbidity and mortality, predominantly due to adverse cardiovascular events. Systemic inflammation in these disorders may alter arterial compliance and arterial distensibility and, through this effect, lead to accelerated atherosclerosis. We have demonstrated an increase in the carotid-femoral (aortic) PWV that is a technique in which large artery elasticity is assessed from analysis of the peripheral arterial waveform, in patients with chronic inflammatory conditions such as RA, SLE, familial Mediterranean fever (FMF), Wegener’s granulomatosis (WG), sarcoidosis, psoriasis and psoriatic arthritis except Behçet’s disease (BD). In this review, the issue of arterial stiffness in RA, SLE, as well as WG, psoriasis, FMF, BD, sarcoidosis, systemic sclerosis (SS) and Takayasu's arteritis (TA) is overviewed.

Arterial distensibility in chronic inflammatory rheumatic disorders.

The pulse wave velocity (PWV), as an indicator of arterial distensibility, may play an important role in the stratification of patients based on the cardiovascular risk. PWV inversely correlates with arterial distensibility and relative arterial compliance. Decreased arterial distensibility alters arterial blood pressure and flow dynamics, and disturbes coronary perfusion. Systemic immune and inflammatory diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with increased morbidity and mortality, predominantly due to adverse cardiovascular events. Systemic inflammation in these disorders may alter arterial compliance and arterial distensibility and, through this effect, lead to accelerated atherosclerosis. We have demonstrated an increase in the carotid-femoral (aortic) PWV that is a technique in which large artery elasticity is assessed from analysis of the peripheral arterial waveform, in patients with chronic inflammatory conditions such as RA, SLE, familial Mediterranean fever (FMF), Wegener’s granulomatosis (WG), sarcoidosis, psoriasis and psoriatic arthritis except Behçet’s disease (BD). In this review, the issue of arterial stiffness in RA, SLE, as well as WG, psoriasis, FMF, BD, sarcoidosis, systemic sclerosis (SS) and Takayasu's arteritis (TA) is overviewed.