CD163 and its role in inflammation Kowal, Krzysztof; Silver, Richard; Sławińska, Emila ...
Folia histochemica et cytobiologica,
01/2011, Letnik:
49, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Mononuclear phagocytes represent a heterogeneous population of cells with individual subpopulations exerting different pro- or anti-inflammatory functions. CD163 is a monocyte/macrophage specific ...marker expressed predominantly on cells which possess strong anti-inflammatory potential. The expression of CD163 is strongly induced by anti-inflammatory mediators such as glucocorticoids and interleukin-10, while being inhibited by pro-inflammatory mediators such as interferon-gamma. CD163-expressing mononuclear phagocytes, as well as soluble CD163, may both take part in downregulating an inflammatory response. It seems, therefore, that CD163 may be an interesting target for therapeutic modulation of the inflammatory response.
The systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are a diseases in which disturbances in plasma proteins glycosylation exist. The aim of the study was to compare the serum profile ...of transferrin isoforms between SLE and SSc. The study was carried out in 38 patients with SLE and 43 patients with SSc. Transferrin isoforms were analyzed by capillary electrophoresis method. Among the transferrin isoforms only the level of pentasialotransferrin in SLE patients was significantly higher than in SSc patients (p = .014). The median concentrations of trisialotransferrin and pentasialotransferrin were significantly lower in SLE patients (p < .001, p = .042; respectively) and SSc (p = .001, p < .001; respectively) than in the healthy subjects. In contrast, the level of tetrasialotransferrin manifested significant increase in comparison to the controls (p < .001 for all comparisons). The serum profile of transferrin isoforms alters in SLE and SSc but only level of pentasialotransferrin differs between SLE and SSc patients. We confirm that the serum profile of transferrin isoforms in SLE and SSc is unique to these diseases.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Objectives
This study aimed to assess the potential role of the TNF superfamily member lymphocyte T-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry ...mediator on T cells (LIGHT) in SSc through evaluation of: skin expression of LIGHT and its receptors, herpesvirus entry mediator and lymphotoxin ß-related receptor, and serum concentration of LIGHT in SSc patients.
Methods
Expression of LIGHT and its receptors was investigated by immunohistochemistry and evaluated semi-quantitatively in skin biopsies from 19 SSc patients and 9 healthy controls. Serum levels of LIGHT were measured using ELISA in 329 patients with SSc and 50 control subjects.
Results
Expression of LIGHT and both receptors was higher in SSc patients compared with controls (P < 0.05 for all comparisons). Patients with early SSc (⩽ 3 years from the first non-Raynaud’s phenomenon symptom) showed higher expression of LIGHT and herpesvirus entry mediator compared with patients with longer disease duration (P < 0.05 for both comparisons). The mean serum concentration of LIGHT was significantly higher in SSc patients compared with the controls (P < 0.05). High serum concentration of LIGHT was associated with male sex, presence of digital ulcers, muscle involvement (defined by elevated serum creatine kinase levels), steroid treatment and lack of ACA. However, in multivariate regression analysis only presence of digital ulcers and creatine kinase elevation were independently associated with serum concentration of LIGHT.
Conclusion
These data provide the first evidence of overexpression of LIGHT and its receptors in SSc and suggest that the LIGHT axis might contribute to the pathogenesis of SSc. Increased serum concentrations of LIGHT seem to reflect vascular injury in SSc.
Patient-reported outcome measures (PROMs) are important for clinical practice and research. Given the high unmet need, our aim was to develop a comprehensive PROM for systemic sclerosis (SSc), ...jointly with patient experts.
This European Alliance of Associations for Rheumatology (EULAR)-endorsed project involved 11 European SSc centres. Relevant health dimensions were chosen and prioritised by patients. The resulting Systemic Sclerosis Impact of Disease (ScleroID) questionnaire was subsequently weighted and validated by Outcome Measures in Rheumatology criteria in an observational cohort study, cross-sectionally and longitudinally. As comparators, SSc-Health Assessment Questionnaire (HAQ), EuroQol Five Dimensional (EQ-5D), Short Form-36 (SF-36) were included.
Initially, 17 health dimensions were selected and prioritised. The top 10 health dimensions were selected for the ScleroID questionnaire. Importantly, Raynaud's phenomenon, impaired hand function, pain and fatigue had the highest patient-reported disease impact. The validation cohort study included 472 patients with a baseline visit, from which 109 had a test-retest reliability visit and 113 had a follow-up visit (85% female, 38% diffuse SSc, mean age 58 years, mean disease duration 9 years). The total ScleroID score showed strong Pearson correlation coefficients with comparators (SSc-HAQ, 0.73; Patient's global assessment, Visual Analogue Scale 0.77; HAQ-Disability Index, 0.62; SF-36 physical score, -0.62; each p<0.001). The internal consistency was strong: Cronbach's alpha was 0.87, similar to SSc-HAQ (0.88) and higher than EQ-5D (0.77). The ScleroID had excellent reliability and good sensitivity to change, superior to all comparators (intraclass correlation coefficient 0.84; standardised response mean 0.57).
We have developed and validated the EULAR ScleroID, which is a novel, brief, disease-specific, patient-derived, disease impact PROM, suitable for research and clinical use in SSc.
The aim of the present study was to determine and compare the concentration of hyaluronic acid (HA) in rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE), and ...its correlation with parameters of disease activity and duration. The hypothesis was that HA should be increased in rheumatic diseases. We also expected that HA could be a marker of disease activity and inflammation in some of these diseases.
The study group comprised 149 patients with RA, SSc and SLE hospitalized in the Department of Rheumatology and Internal Diseases, Medical University of Bialystok (Bialystok, Poland) and 30 healthy controls. The concentrations of HA, C-reactive protein (CRP) and rheumatoid factor (RF) were measured using Architect ci8200; haemoglobin, platelets on Sysmex XS-800i; and erythrocyte sedimentation rate (ESR) on Sediplus S 2000 analysers. Statistical analysis was performed using Statistica 13.3 PL.
Hyaluronic acid was increased in RA, SLE and SSc when compared to controls (P < 0.001, P = 0.011, and P = 0.015, respectively). There were no differences in HA between rheumatic diseases (P = 0.840). Hyaluronic acid positively correlated with SLE activity (P = 0.025). In RA, HA positively correlated with ESR (P = 0.028) and CRP (P = 0.009). However, HA was not found to correlate with the duration of rheumatic diseases.
Hyaluronic acid concentration undergoes changes in rheumatic diseases with no difference between RA, SLE and SSc. In RA, HA concentration can be a marker of inflammation, while in SLE patients an indicator of disease activity.
To determine whether joint synovitis and tendon friction rubs (TFRs) can predict the progression of systemic sclerosis (SSc) over time.
We performed a prospective cohort study that included 1301 ...patients with SSc from the EUSTAR database with disease duration ≤3 years at inclusion and with a follow-up of at least 2 years. Presence or absence at clinical examination of synovitis and TFRs was extracted at baseline. Outcomes were skin, cardiovascular, renal and lung progression. Overall disease progression was defined according to the occurrence of at least one organ progression.
Joint synovitis (HR: 1.26, 95% CI 1.01 to 1.59) and TFRs (HR: 1.32, 95% CI 1.03 to 1.70) were independently predictive of overall disease progression, as were also the diffuse cutaneous subset (HR: 1.30, 95% CI 1.05 to 1.61) and positive antitopoisomerase-I antibodies (HR: 1.25, 95% CI 1.02 to 1.53). Regarding skin progression, joint synovitis (HR: 1.67, 95% CI 1.06 to 2.64) and TFRs (HR: 1.69, 95% CI 1.02 to 2.77) were also independently predictive of worsening of the modified Rodnan skin score. For cardiovascular progression, joint synovitis was predictive of the occurrence of new digital ulcer(s) (HR: 1.45, 95% CI 1.08 to 1.96) and decreased left ventricular ejection fraction (HR: 2.20, 95% CI 1.06 to 4.57); TFRs were confirmed to be an independent predictor of scleroderma renal crisis (HR: 2.33, 95% CI 1.03 to 6.19).
Joint synovitis and TFRs are independent predictive factors for disease progression in patients with early SSc. These easily detected clinical markers may be useful for the risk stratification of patients with SSc.
Systemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc ...and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc.
Patients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis.
3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41 (1.91 to 3.03), p<0.001, for an elevated systolic pulmonary arterial pressure on heart ultrasound (US-PAPs):1.36 (1.03 to 1.80), p=0.032, for any cardiovascular event (new DUs, elevated US-PAPs or LV failure): 3.56 (2.26 to 5.62), p<0.001, and for death (1.53 (1.16 to 2.02), p=0.003).
In patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival.
To identify predictive parameters for the progression of skin fibrosis within 1 year in patients with diffuse cutaneous SSc (dcSSc).
An observational study using the EUSTAR database was performed. ...Inclusion criteria were dcSSc, American College of Rheumatology (ACR) criteria fulfilled, modified Rodnan skin score (MRSS) ≥7 at baseline visit, valid data for MRSS at 2nd visit, and available follow-up of 12±2 months. Worsening of skin fibrosis was defined as increase in MRSS >5 points and ≥25% from baseline to 2nd visit. In the univariate analysis, patients with progressive fibrosis were compared with non-progressors, and predictive markers with p<0.2 were included in the logistic regression analysis. The prediction models were then validated in a second cohort.
A total of 637 dcSSc patients were eligible. Univariate analyses identified joint synovitis, short disease duration (≤15 months), short disease duration in females/patients without creatine kinase (CK) elevation, low baseline MRSS (≤22/51), and absence of oesophageal symptoms as potential predictors for progressive skin fibrosis. In the multivariate analysis, by employing combinations of the predictors, 17 models with varying prediction success were generated, allowing cohort enrichment from 9.7% progressive patients in the whole cohort to 44.4% in the optimised enrichment cohort. Using a second validation cohort of 188 dcSSc patients, short disease duration, low baseline MRSS and joint synovitis were confirmed as independent predictors of progressive skin fibrosis within 1 year resulting in a 4.5-fold increased prediction success rate.
Our study provides novel, evidence-based criteria for the enrichment of dcSSc cohorts with patients who experience worsening of skin fibrosis which allows improved clinical trial design.
In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly ...known. Therefore, we aimed to determine sex effects on outcomes.
We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival.
9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p<0.001), a higher frequency of digital ulcers (OR: 1.28 (1.11 to 1.47); p<0.001) and pulmonary hypertension (OR: 3.01 (1.47 to 6.20); p<0.003). In the longitudinal analysis (n=4499), after a mean follow-up of 4.9 (±2.7) years, male sex was predictive of new onset of pulmonary hypertension (HR: 2.66 (1.32 to 5.36); p=0.006) and heart failure (HR: 2.22 (1.06 to 4.63); p=0.035). 908 deaths were recorded, male sex predicted deaths of all origins (HR: 1.48 (1.19 to 1.84); p<0.001), but did not significantly account for SSc-related deaths.
Although more common in women, SSc appears as strikingly more severe in men. Our results obtained through the largest worldwide database demonstrate a higher risk of severe cardiovascular involvement in men. These results raise the point of including sex in the management and the decision-making process.
Systemic sclerosis (scleroderma, SSc) is a chronic connective tissue disease of unknown etiology characterized by progressive fibrosis of the skin and a distinctive pattern of internal organ ...involvement. Excessive fibrosis, vascular injury, autoimmunity and inflammation are permanent features of the disease process leading to irreversible organ damage and significant morbidity and mortality in SSc patients. Recent progress in understanding the pathogenesis of SSc as well as diagnostic and therapeutic advances in medicine have made more effective treatment strategies possible. So far, therapies targeting vascular aspects of SSc have been most successful. This underlines the role of vascular injury in the pathogenesis of the disease and raising hopes of significant improvement in the management of SSc patients. The aim of this review is to summarize recent and potential future treatments of SSc-associated vascular disease.
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