Serum level of interleukin-33 in rheumatoid arthritis patients and its association with bone erosion and interstitial lung disease

Aim of the workTo analyze the serum levels of IL-33 in RA patients and to investigate its relation to the clinical characteristics, laboratory investigations, joint erosions, functional status and disease activity. Its relation to the presence of interstitial lung disease (ILD) was well thought-out.Patients and methodsThe study included 50 RA patients and 30 matched control. Thorough clinical examination, investigations, disease activity score (DAS-28) and health assessment questionnaire (HAQ) were considered in the patients. Bone erosion was evaluated and interstitial lung disease (ILD) was identified on high-resolution computed tomography. The serum level of IL-33 was measured by enzyme-linked immunosorbent assay.ResultsSerum levels of IL-33 are significantly higher in RA patients (106.96 ± 52.6 pg/ml) than in healthy controls (46.9 ± 23 pg/ml) (p < 0.001). A significant correlation was found between IL-33 and the DAS28 (r = 0.4, p = 0.001), level of rheumatoid factor (r = 0.45, p = 0.001) and with the presence of ILD (r = 0.3, p = 0.04). There were no gender differences and the level did not significantly correlate with the age or disease duration. The medications received had no obvious effect on the IL-33 level. The level did not correlate with the HAQ. There was a significant correlation between the CT bone erosion scores the patient’s age, disease duration, rheumatoid nodules and DAS28. The erosion score also significantly correlated with the serum IL-33 levels in RA patients (r = 0.71, p = 0.001).ConclusionThese data support the hypothesis that IL-33 may be involved in RA pathogenesis and it may partly contribute to the bone erosion and ILD in RA patients.     

Th-17 cells and serum IL-17 in rheumatoid arthritis patients: Correlation with disease activity and severity

Aim of the workTo investigate the role of T-helper 17 (Th17) cells in peripheral blood and serum interleukin-17 (IL-17) in rheumatoid arthritis (RA) patients, and their correlation with disease activity and joint destruction.Patients and methodsThis study included forty RA patients and twenty matched healthy controls. Disease activity score in 28 joints (DAS-28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP, tumor necrosis factor alpha (TNF-α), serum IL-17 and Th17 cells in peripheral blood were measured. Radiological assessment using modified Sharp/van der Heijde (mSvH) score for hand and feet in addition to MRI score for the wrist and metacarpophalangeal (MCP) joints were performed for detection of synovitis and bone erosion.ResultsThe patients were 38 females and 2 males with a mean of 41.15 ± 5.85 years and disease duration of 15.6 ± 4.62 years. Serum IL-17 and Th17 cells in peripheral blood were found to be significantly increased in RA patients (204.1 ± 33.8 pg/ml and 4.62 ± 1.13%) than in controls (25.36 ± 5.39 pg/ml and 0.7 ± 0.021%) (p < 0.001). Th17 cells significantly correlated with serum IL-17 (r 0.88, p < 0.001). Both Th17 cells and serum IL-17 significantly correlated with DAS-28, ESR, CRP, TNF-α, Van der Heijde modification score and MRI scores for wrist and MCP joints for synovitis and bone erosion (all with a p < 0.001).ConclusionThis study demonstrates an important role for Th-17 cells and serum IL-17 in the pathogenesis of the inflammatory and destructive pattern characteristic of RA.     

The relationship of serum leptin levels with disease activity in Egyptian patients with rheumatoid arthritis

Aim of the workTo investigate whether serum leptin levels are elevated in patients with rheumatoid arthritis (RA) and whether these levels correlate with disease activity.Patients and methodsA case-control study was made on 37 patients with RA and 34 healthy control subjects. The following values were assessed for each patient: erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF), swollen and tender joint counts, disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), visual analog scale (VAS) of pain and serum leptin concentrations.ResultsPatients with RA had mild to moderate (DAS28 < 5.1) disease activity. The mean serum leptin in patients with RA (12.15 ± 11.48 ng/mL) was significantly higher (p < 0.001) than controls (3.99 ± 1.84 ng/mL). Serum leptin levels were significantly (p < 0.001) higher in female RA patients than in female controls. A nonsignificant difference (p = 0.41) was found between male patients with RA and male controls. Serum leptin levels were significantly (p < 0.001) higher in women than in men in both patients and controls. Serum leptin levels did not show correlation with age, disease duration, duration of morning stiffness, VAS, number of swollen and tender joints, DAS28, HAQ, ESR or CRP in patients with RA. Serum leptin levels were correlated positively with BMI in RA patients. The BMI was significantly higher (p < 0.001) in female than in male patients with RA.ConclusionAlthough leptin levels were higher in RA patients, there was no correlation with disease activity parameters, therefore, leptin levels cannot be used to reflect disease activity.     

Vitamin D levels in patients with Behçet’s disease: Significance and impact on disease measures

Aim of the workThis study aimed to investigate serum levels of vitamin D in patients with Behçet’s disease (BD) and to evaluate their relationship to disease activity as well as different disease measures.Patients and methodsForty-two patients with BD were enrolled into this study. These patients were subjected to detailed history taking, thorough clinical examination including assessment of disease activity according to Behçet’s Disease Current Activity Form (BDCAF) score and performed laboratory investigations including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum calcium, serum phosphorus and serum alkaline phosphatase. Serum 25-hydroxyvitamin D (vitamin D) levels were determined using Enzyme-Linked-Immunosorbent Assay (ELISA). A control group of 41 age and sex matched healthy controls was also included.ResultsThe mean level of 25-hydroxyvitamin D (30.65 ± 12.87 ng/ml) was significantly decreased in BD patients compared to the controls (37.98 ± 15.76 ng/ml) (p = 0.02). Significant negative correlations of serum vitamin D levels with patients’ ages (p = 0.03), ESR (p < 0.001), CRP (p < 0.001) and BDCAF (p = 0.003) were found; whereas, there was no significant correlation with disease duration (p = 0.6). In multivariate regression analysis age (p = 0.02), colchicine therapy (0.008), ESR (0.02) and CRP (0.03) were found to be the independent effectors on vitamin D serum levels.ConclusionSerum levels of vitamin D were significantly lower in BD patients compared to controls. Associations were found between vitamin D levels and age, BDCAF as well as ESR and CRP in BD patients. Low vitamin D may predispose BD patients to active disease, especially in older subjects.     

Significance of serum levels of angiopoietin-2 and its relationship to Doppler ultrasonographic findings in rheumatoid arthritis patients

BackgroundAngiopoietin-2 (Ang-2) is connected to angiogenesis in synovial regions, but the significance of its levels in patients with rheumatoid arthritis (RA) is still unclear.Aim of the workTo evaluate the significance of serum levels of Ang-2 in patients with RA. Also, to determine Ang-2 relationship to the findings of joints Doppler ultrasonographic findings.Patients and methodsThis study included 40 patients with RA, and 25 matched healthy controls. All patients were subjected to assessment of pain using visual analogue scale (VAS), assessment of personal activity using the Health Assessment Questionnaire (HAQ) score, and calculation of disease activity score (DAS 28). Laboratory assays of complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) titre, and measurement of serum levels of Ang-2 by ELISA. Doppler ultrasonography (US) assessment for eight joints, with calculation of synovial thickness and total signal score (TSS), was done.ResultsSerum Ang-2 levels were significantly higher among patients (3191.3 ± 594.9 pg/ml) than controls (1771.7 ± 103.1 pg/ml) (p < 0.001). Serum Ang-2 levels were significantly correlated with ESR, CRP, DAS28, and duration of morning stiffness (p < 0.001, p < 0.001, p < 0.001, and p = 0.025, respectively). There was a significant correlation between serum Ang-2 levels and findings of US, regarding joint synovial thickness, and TSS (p < 0.001, for both).ConclusionPatients with RA had significantly higher levels of serum Ang-2 versus controls. In those patients, serum Ang-2 levels were significantly correlated with disease activity markers (ESR, CRP), DAS28, and duration of morning stiffness. Moreover, these levels were significantly correlated with synovial thickness, and TSS. The role of Ang-2 in RA pathogenesis might open the door to the development of new therapeutic strategies, particularly which target angiogenesis.     

Proteinase-activated receptor 2 expression on peripheral blood monocytes and T-cells in patients with rheumatoid arthritis

Aim of the workProteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. The aim of this work was to evaluate the expression of PAR2 on peripheral blood monocytes and T-cells in rheumatoid arthritis (RA) patients and its correlation with disease activity.Patients and methodsForty RA patients and 16 healthy controls were enrolled in this study. Flow cytometry was performed to detect PAR2 expression. Disease activity score (DAS28) was assessed.ResultsPAR2 expression was significantly higher on monocytes in RA patients with active disease compared with patients in remission and healthy controls (75.4 ± 7.68; 56 ± 13.93 and 46.5 ± 9.8 respectively; p < 0.001). It was higher in RA patients in remission compared to healthy control (p = 0.01). No significant difference was found between patients with moderate and high disease activity. It significantly correlated with the erythrocyte sedimentation rate (ESR) and DAS28 (p < 0.001). It was significantly higher in patients with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positivity (p = 0.01, p < 0.001, respectively). It was not significantly associated with C-reactive protein (CRP) positivity and was not significantly different between early and long standing RA patients. PAR2 expression on CD3⁺ T-cells was not significantly different between patients with RA disease activity, patients in remission and healthy controls. Also it was not significantly associated with the ESR, DAS28, anti-CCP, RF and CRP positivity.ConclusionPAR2 expression on monocytes is consistent with a pathogenic role for PAR2 in RA and suggests that PAR2 may have utility as a marker for RA disease activity.     

Does treatment affect the levels of serum Interleukin-6, Interleukin-8 and procalcitonin in diabetic foot infection? A pilot study

AimsTo investigate about serum PCT, IL-6 and IL-8 levels and how they are affected by the treatment in diabetic foot patients.MethodsFifty patients’ blood samples were taken to study ESR and CRP, IL-6, IL-8 and PCT before and at the 14th day of the treatment.ResultsThe pretreatment results of the 50 patients showed positive correlations between PCT and either ESH (r = 0.49, p < 0.001), or CRP (r = 0.56, p < 0.001). Similarly, there was a positive correlation between IL-6 and ESH (r = 0.46, p = 0.001), just like as it was between IL-6 and CRP (r = 0.54, p < 0.001). At the 14th day, the levels of ESR (70 ± 30.2 and 58.4 ± 26.2, p = 0.02), CRP (63.8 ± 73.1 and 18.1 ± 19.7, p < 0.001) and PCT (0.6 ± 2.1 and 0.05 ± 0.02, p = 0.007) were significantly decreased while IL-6 was decreased at a close range to statistical significancy at healing patients (97.5 ± 147.2 and 47.1 ± 77.6; p = 0.05), but they did not at nonhealing patients. IL-8 levels were not changed anyhow.ConclusionsPCT was significantly decreased such as ESR and CRP were in the early phase of healing; IL-6 and IL-8 levels were also decreased by the treatment, but not statistically significantly. IL-6 and PCT were affected in correlation with the other inflammatory parameters in the beginning, but IL-8 was not. PCT and IL-6 may be useful like CRP and ESR in the diagnosis and follow up of diabetic foot infection, but IL-8 is not. Further investigation is needed.     

Osteoprotegerin (OPG) and Matrix Gla protein (MGP) in rheumatoid arthritis patients: Relation to disease activity

BackgroundImbalanced Matrix Gla protein (MGP) and Osteoprotegerin (OPG) levels occur in inflammatory diseases.Aim of the workThe aim of the present study was to evaluate serum MGP and OPG levels in Rheumatoid Arthritis (RA) patients and study their relation to the disease activity.Patients and methodsForty-five female RA patients and 45 age and sex-matched healthy controls were included in this study. Disease activity score 28-C-reactive protein (DAS28-CRP) was used for the assessment of disease activity. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), MGP and OPG were measured in patients and controls. The associations of MGP and OPG with DAS28-CRP and the other laboratory and clinical variables were analyzed.ResultsRA patients had significantly higher serum OPG levels (408.3 ± 520.9 pg/ml) and hs-CRP (2.8 ± 1.9 mg/l) than the control (92.5 ± 86.3 pg/ml and 0.9 ± 1.5 mg/l respectively) (p < 0.001 each). There was no significant difference in MGP levels between the patients and control (p = 0.3). The correlation of OPG and MGP with DAS28-CRP in the patients was insignificant (p = 0.4 and p = 0.8 respectively). Age positively correlated with OPG (r = 0.32, p = 0.02), but not with MGP concentration (r = 0.05, p = 0.64) in the RA patients.ConclusionsThe significant elevation of the OPG level in RA patients may through light on its possible role in the pathogenesis of this disease and could be considered as a future therapeutic target. The significant correlation with age suggests that OPG may be an important mediator especially in elderly RA cases.     

Association of asymptomatic hyperuricemia and endothelial dysfunction in psoriatic arthritis

IntroductionCardiovascular disease is an increasingly recognized contributor to excess morbidity and mortality in psoriatic arthritis (PsA). Traditional cardiovascular risk factors do not adequately account for the extent of cardiovascular disease in PsA.Aim of the workTo examine the prevalence of subclinical atherosclerosis in patients with PsA to emphasize the potential role of serum uric acid on endothelial dysfunction, as an early predictor for atherosclerosis in PsA patients.Patients and methodsThis study included 60 PsA patients as well as 60 age and sex matched healthy controls. Assay of serum uric acid, interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) was done for all patients and controls. Patients were subjected to psoriasis area severity index (PASI) and assessment of disease activity. Patients and controls underwent brachial flow-mediated dilatation (FMD) assessment by color duplex sonography to determine endothelial dysfunction as well as extracranial carotid arteries assessment by high-resolution B-mode ultrasound to measure the common carotid intima-media thickness (CIMT) and the detection of atheromatous plaques.ResultsPsA patients have a high significant difference in CIMT, FMD of the brachial artery and mean levels of serum uric acid compared to healthy controls (p < 0.001). PsA patients with hyperuricemia have a high significant difference in CIMT and FMD of the brachial artery than those with normal serum uric acid. Serum uric acid levels showed a high significant positive correlation with each of CIMT, disease duration, markers of inflammation (ESR, CRP, IL-6, sICAM-1), disease activity score in 28 joints (DAS 28) and PASI (r = 0.71, 0.893, 0.956, 0.858, 0.853, 0.877, 0.907, 0.847, respectively, as p < 0.001). A high significant negative correlation was found between serum uric acid levels and FMD of the brachial artery as r = ?0.634, p < 0.001.ConclusionPatients with PsA have a high prevalence of subclinical atherosclerosis dependent on serum uric acid, suggesting that chronic systemic inflammation and endothelial dysfunction appear to be the link between asymptomatic hyperuricemia and atherosclerosis. Therefore, proper control of serum uric acid may play a preventive role in the development of atherosclerosis in PsA patients.     

Relation between serum IL-17 level and risk of osteoporotic fracture in premenopausal rheumatoid arthritis patients: Clinical,radiological and laboratory studies

IntroductionOsteoporosis is a main extra-articular complication of rheumatoid arthritis (RA) which may lead to fractures. Interleukin-17 (IL-17) is one of the cytokines which plays a significant role in RA pathogenesis and promotion of osteoporosis.Aim of the workTo study the relation between serum IL-17 levels and the risk of osteoporotic fractures in pre-menopausal RA patients.Patients and methodsTwenty-five premenopausal RA patients and 20 matched healthy controls were included in this study. All patients were subjected to detailed history taking, thorough clinical examination, disease activity assessment using the disease activity score-28 (DAS-28) and disability was assessed using Health Assessment Questionnaire–Disability Index (HAQ-DI). Bone mineral density and serum IL-17 levels were measured in patients and the control. Fracture Risk Assessment Tool (FRAX index) was also calculated.ResultsThe mean age of RA patients was 38.8 ± 7.6 years. The BMD was significantly reduced in patients compared to the control at the femur neck (p = 0.008), wrist (p = 0.046) and at the lumbar spine (p = 0.005). The Z score was below the expected range for age in 36% compared to 5% in the control (p = 0.03). Serum IL-17 concentrations were significantly higher in patients (5.99 ± 1.22 pg/ml) compared to the control (3.73 ± 2.15 pg/ml) (p < 0.001). Serum IL-17 levels showed a significant correlation with FRAX scores. Z-score interpretation showed a strong positive significant correlation with FRAX index; major osteoporotic fractures and hip fracture (p = 0.005 and p = 0.013, respectively) in patients.ConclusionThe premenopausal Rheumatoid arthritis patients showed a high fracture probability. Interleukin-17 serum level is associated with higher liability to fractures among rheumatoid patients.     

CXC ligand 13 in rheumatoid arthritis and its relation to secondary Sjögren’s syndrome

Aim of the workThe aim of the present study was to measure the level of the chemokine CXC ligand 13 protein (CXCL13) in the plasma and unstimulated saliva of rheumatoid arthritis (RA) patients in order to find out its role in the disease activity and its relation to secondary Sjögren’s syndrome (sSS).Patients and methodsThe study was conducted on thirty rheumatoid arthritis patients attending the Outpatient Clinic of Rheumatology and Rehabilitation department of Ain shams University Hospitals. The patients’ group had been classified into group (1) which included fifteen RA patients associated with sSS diagnosed according to the American–European Consensus Group Classification Criteria and group (2) which included fifteen RA patients not associated with sSS. Ten healthy subjects were included as a control group. Patients were subjected to full history taking, clinical examination, and laboratory detection of CXCL13 level in the plasma and saliva of patients as well as the control groups using ELISA technique. Assessment of disease activity in RA patients was done using the disease activity score (DAS28).ResultsPlasma levels of CXCL13 were significantly higher in RA patients than control group (p < 0.001). Plasma levels of CXCL13 were significantly correlated with the RA disease activity (r = 0.677, p < 0.001) and disease duration (r = 0.406, p < 0.05), while the salivary levels were higher in those with sSS and correlated with sSS disease duration (r = 0.536, p < 0.05). A highly significant correlation was found between salivary CXCL13 and severity of sSS (r = 0.816, p < 0.001). Salivary levels of CXCL13 above 110 pg/ml may diagnose sSS with sensitivity 80% and specificity 84%.ConclusionThe results of this preliminary study point out the importance of CXCL13 as a marker for RA disease activity, its role in diagnosing sSS, and estimation of sSS severity.     

Abdominal obesity and low-grade systemic inflammation as markers of subclinical organ damage in type 2 diabetes

AimThis study aimed to explore the associations between abdominal obesity, inflammatory markers and subclinical organ damage in 740 middle-aged patients with type 2 diabetes.MethodsWaist circumference (WC) and sagittal abdominal diameter (SAD) were measured, and blood samples were analyzed for C-reactive protein (CRP) and IL-6. Carotid intima–media thickness (IMT) was evaluated by ultrasonography, and aortic pulse wave velocity (PWV) measured with applanation tonometry.ResultsAbdominal obesity as determined by SAD and WC was significantly correlated with IL-6 (WC: r = 0.27, P < 0.001; SAD: r = 031, P < 0.001), CRP (WC: r = 0.29, P < 0.001; SAD: r = 0.29, P < 0.001), IMT (WC: r = 0.09, P = 0.013; SAD: r = 0.11, P = 0.003) and PWV (WC: r = 0.18, P < 0.001; SAD: r = 0.21, P < 0.001). In multiple linear regressions with IMT and PWV as dependent variables, and age, gender, statin use, systolic blood pressure (SBP), body mass index (BMI), CRP and HbA_1c as independent variables, both SAD and WC remained associated with IMT and PWV. On stepwise linear regression and entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.ConclusionBoth SAD and WC are feasible measures of obesity, and both provide information on inflammation, atherosclerosis and arterial stiffness in type 2 diabetes, while SAD appears to be slightly more robustly associated with subclinical organ damage than WC.     

Assessment of synovitis in early rheumatoid arthritis by CXCL13 serum levels and power Doppler ultrasonography: Correlation with disease activity

Aim of the workAssessment of synovitis in rheumatoid arthritis (RA) is a major issue for proper treatment; it has been proven that high resolution ultrasound (US) examination could be of valuable help. The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. We aimed to find out the presence of synovitis in patients with recent-onset RA and its correlation with disease activity.Patients and methodsWe evaluated 30 patients with early RA for the presence and degree of synovitis by performing high resolution US and obtaining serum CXCL13 levels. In addition, we correlated these results with disease activity score 28 (DAS 28). Results of high resolution US and serum CXCL13 were also obtained for 20 healthy age- and sex-matched volunteers and served as controls.ResultsSerum CXCL13 level was significantly increased in early RA patients vs. controls (p < 0.001). High resolution US revealed that RA patients had a significant increased synovial thickness and high power Doppler US score. In RA patients, DAS 28 had a significant correlation with serum CXCL13 (r = 0.42, p = 0.02), synovial thickness (r = 0.39, p = 0.03) and power Doppler US score (r = 0.43, p = 0.02). Serum CXCL13 level correlated with synovial thickness (r = 0.63, p = 0.001) and power Doppler US score (r = 0.69, p = 0.001).ConclusionRecent-onset RA patients suffer from synovitis as evidenced by significantly increased serum CXCL13 and by high resolution US. Serum CXCL13 is a reliable marker of synovial inflammation which correlates better with synovial thickening and power Doppler US scores than DAS28.     

Insulin resistance as a risk factor for subclinical atherosclerosis in rheumatoid arthritis

BackgroundInsulin resistance (IR) is strongly associated with systemic inflammation. Insulin resistance is known to be increased in patients with rheumatoid arthritis (RA) and has been shown to be a risk factor for both clinical cardiovascular disease and subclinical atherosclerosis.Aim of the workTo study the relationship between insulin resistance, disease activity and subclinical atherosclerosis in RA patients.Patients and methodsForty RA patients and twenty age and sex matched healthy individuals as controls were included. Patients with diabetes mellitus, obesity and hypertension were excluded. Fasting plasma sugar and serum insulin were done, RA disease activity was assessed using the disease activity score (DAS28) and IR was evaluated by the homeostasis model assessment (HOMA2). Carotid artery intima media thickness (IMT) was evaluated using ultrasound.ResultsRA patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) positivity, fasting plasma sugar and fasting serum insulin, HOMA2-IR levels than the controls. IR was present in 33 (82.5%) RA patients while it was present in only one (10%) of the controls (p = 0.001). RA patients with IR had significantly longer disease duration (p = 0.003), higher disease activity (p = 0.000), greater carotid IMT (p = 0.000), and more carotid plaques (p = 0.043) than those without insulin resistance. RA patients with increased IMT had significantly longer disease duration (p = 0.002), higher DAS28 score (p = 0.000) and higher HOMA2-IR (p = 0.000) than those with normal IMT.ConclusionsIn RA patients, IR significantly correlated with both disease activity and disease duration. Our study pointed out a significant association between IR and subclinical atherosclerosis in RA.     

Hepcidin is a key mediator of anemia of inflammation in Crohn's disease

Anemia often complicates the course of Inflammatory Bowel Disease (IBD). Hepcidin, a liver-produced peptide hormone, is a key mediator of anemia of chronic disease (ACD). We hypothesized that hepcidin is significantly elevated in anemic CD patients and that hepcidin may cause iron restriction and, therefore, mediate ACD.MethodsWe enrolled 17 patients with CD and ACD recruited from the Cedars-Sinai IBD Center. Routine blood tests included hemoglobin (Hgb), hematocrit, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Anemia was defined as hemoglobin < 12 g/dL and < 13.5 g/dL, in men and women, respectively. ACD was diagnosed on the basis of a combination of the following: a) normal or elevated ferritin b) lowered serum iron and total iron binding capacity and c) normal percent iron saturation. Serum and urine hepcidin, as well as IL-6 levels were also measured. Patients with documented iron-deficiency anemia were excluded.ResultsThere was an excellent correlation between urine (expressed as ng/mg of creatinine) and serum hepcidin levels expressed as ng/ml (r = 0.853, p < 0.001). We also found a strong positive correlation between serum hepcidin and ferritin levels (r = 0.723, p = 0.0015). There was a positive correlation between serum hepcidin and IL-6 levels (r = 0.546, p = 0.023). We found a strong negative correlation between serum hepcidin concentrations and Hgb levels (r = 0.528, p = 0.029).ConclusionWe demonstrate that ACD in CD is characterized by high serum IL-6 and hepcidin levels, which negatively correlate with Hgb levels. Our data support the hypothesis that IL-6-driven hepcidin production mediates ACD in patients with CD.     

Intra-renal hemodynamics and carotid intima-media thickness in the metabolic syndrome

AimsMetabolic syndrome (MetS) is associated with increased cardiovascular risk. We hypothesize that early vascular changes are already present at the time of diagnosis of MetS. The relationship of different measures of early vascular impairment with body fat distribution and the natural progression of MetS was examined in newly diagnosed subjects non-pharmacologically treated.Methods246 consecutively enrolled subjects were categorized according to the presence of MetS and type 2 diabetes (T2D). Intra-renal Doppler flow was used to ascertain resistive (RI) and pulsatility (PI) indices as markers of vascular resistance. Carotid intima-media thickness (IMT), cutis-rectis (CR) and rectis-aorta (RA) thicknesses were measured by ultrasonography; RA/CR ratio was used as measure of body fat distribution. Pro-inflammatory cytokines, C-reactive protein, oxidative markers insulin and adiponectin blood concentrations were also measured.ResultsBaseline characteristics demonstrated increasing trends in biochemical, inflammatory, and oxidative parameters from MetS−, MetS+, to MetS+/T2D (p < 0.001). After adjusting for age, the same increasing trends across the groups were observed in both sexes in IMT (p < 0.001), RI (p < 0.001) and PI (p < 0.001). IMT correlated with RI (r = 0.25; p < 0.001), PI (r = 0.26; p < 0.001), and RA/CR ratio (r = 0.43; p < 0.001).ConclusionsCarotid IMT and intra-renal resistances are elevated at an early stage in MetS and are associated with a dysregulated production of fat-derived hormones and cytokines.     

Clinical significance of serum interleukin-6 and −174 G/C promoter polymorphism in Rheumatoid arthritis patients

Aim of the workTo evaluate the clinical significance of serum levels of interleukin-6 (IL-6) and ?174 G/C promoter polymorphism in Rheumatoid arthritis (RA) patients.Patients and methodsWe studied 37 RA patients and 10 age and gender matched healthy controls. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) were assessed. Serum IL-6 level was measured and promoter (?174G/C) genotyped.ResultsSerum IL-6 levels were significantly higher in RA patients compared to control (p = 0.04), especially those with CC promoter polymorphism. Twenty-four patients had GG IL-6 (?174 G/C) gene promoter polymorphism, 11 were GC and 2 CC. Nine controls were GG and 1 GC. In patients with more advanced polymorphism (?174 CC) there was a significantly increased functional impairment (HAQ score) (p = 0.029) and platelet count (p = 0.049). In those with GG genotype, there was a significant correlation between IL-6 and Morning stiffness duration (r = 0.44,p = 0.03), while those with GC genotype had a significant negative correlation of the IL-6 level with the parameters of disease activity and the DAS28 (r = ?0.69,p = 0.019). None of the studied parameters would predict the IL-6 promoter polymorphism.ConclusionSerum IL-6 levels and ?174 G/C promoter polymorphism were higher in RA patients than in healthy controls. The inverse relation of IL-6 with the DAS28 in those with an increased IL-6 promoter polymorphism may confirm its increased involvement in the pathogenesis of RA and in the increased disease activity which may point to the need for considering of anti-IL-6 agents in their management plan.     

Red cell distribution width and mean platelet volume in rheumatoid arthritis patients: Its association with disease activity

IntroductionHemogram parameters have been recently proposed as markers of inflammation in various studies from different parts of the world. Two of these hemogram parameters are red cell distribution width (RDW) and mean platelet volume (MPV).AimTo evaluate the relation between RDW and MPV with disease activity of rheumatoid arthritis. To assess whether RDW and MPV can be used to follow disease activity in RA patients.MethodsThis is an observational cross-sectional study that was carried out on 60 rheumatoid arthritis patients who fulfilled the ACR/EULAR2010 classification criteria of RA attending to Rheumatology and Rehabilitation inpatient and outpatient clinics at Zagazig University Hospitals. All cases were subjected to full history taking, clinical examination, and laboratory investigations; differential complete blood picture (CBC), acute phase reactants (CRP and ESR), rheumatoid factor (RF) and anti-cyclic-citrullinated peptide (anti-CCP) antibodies. Disease activity was measured by disease activity score 28 (DAS28).ResultsThe cut-off levels of RDW and MPV were 14.85 and 11.25. Patients with RDW > 14.85 had higher Disease Activity Score 28 (DAS28; p = 0.0003), ESR (p = 0.0001) and CRP (p = 0.0001). RDW was positively correlated with disease activity markers (ESR, CRP and DAS28) in rheumatoid arthritis patients. But, DAS28 was not different between patients with MPV > 11.25 and <11.25.ConclusionRDW was strongly correlated with disease activity. Also, RDW was better than ESR and CRP in detecting RA disease activity. According to these findings we suggest that RDW can be used in clinics to follow disease activity. In addition, RDW is widely available; as it's usually included in routine complete blood picture and there will be no need for further cost.     

Cytokine mucosal expression in ulcerative colitis,the relationship between cytokine release and disease activity

BackgroundUlcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFα, IL-8, TGFβ and other cytokines and characterised by neutrophil infiltration and tissue destruction.AimTo compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls.MethodsPatients were prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age–sex matched controls undergoing FS. Endoscopic and histological inflammation was graded. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8, IL-10, TGFβ and IFNγ was carried out on tissue homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis, Mann–Whitney U test and Spearman's correlation.Results69 active UC patients (54 paired non-inflamed/inflamed mucosa) and 69 controls were compared. In inflamed mucosa, elevation in IL-8 and reduction in TGFβ was measured compared with non-inflamed mucosa (p < 0.001; p < 0.02) and control mucosa (p < 0.001; p < 0.001); IL-8 was positively correlated (r_s = 0.481, p < 0.01) and TGFβ inversely correlated (r_s = 0.462; p < 0.01) with grade of inflammation. TNFα concentration was not significantly different. Comparisons of inflamed with non-inflamed mucosa also demonstrate significant reduction in concentration of IFNγ (p < 0.001), IL-4 (p < 0.005) and IL-17A (p < 0.002).ConclusionOur findings suggest that IL-8 is elevated and TGFβ is reduced in distal colitis. Lower concentration of IFNγ, IL-4 and IL-17A were also noted. TNFα levels were unchanged. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGFβ mediated tissue healing.     

Angiopoietin-2 as a biomarker for metabolic syndrome and disease activity in rheumatoid arthritis patients

BackgroundThe incidence of metabolic syndrome (MetS) increases in rheumatoid arthritis (RA) patients which increases the risk of cardiovascular disease (CVD). Angiopoietin-2 levels increase in RA and were reported to predict CVD.Aim of the workTo assess the level of angiopoietin-2 in RA patients and study its relation to disease activity and its role in those with MetS.Patients and methodsThe study included 80 RA patients (67 females and 13 males) and 20 healthy age and sex matched controls. The patients were divided into Group 1 (n = 40) with MetS and Group 2 (n = 40) without. Data were collected throughout history, basic clinical examination and investigation. Disease activity score (DAS-28) was assessed in all patients. Enzyme linked immunosorbent assay was used for the estimation of angiopoietin-2.ResultsThe age and disease duration of those with MetS (40.7 ± 7.23 years and 9.63 ± 6.73 years respectively) and those without (38.6 ± 9.2 and 8.65 ± 5.52 years respectively) were comparable (p = 0.26 and p = 0.48 respectively). The disease activity (DAS-28) was also similar in both groups (5.12 ± 0.77 and 5.01 ± 0.96 respectively; p = 0.56). There was a significant increase in the angiopoietin-2 levels in RA patients with MetS (5.31 ± 0.56 ng/ml) than those without (4.93 ± 0.44 ng/ml) (p < 0.001). The levels were significantly higher than those of the control (4.44 ± 0.29 ng/ml) (p < 0.001). The angiopoietin-2 level significantly correlated with the DAS-28 (r = 0.23, p = 0.045), systolic (r = 0.36, p = 0.001) and diastolic blood pressure (r = 0.35, p = 0.001), fasting blood sugar (r = 0.29, p = 0.009) and triglycerides (r = 0.24, p = 0.03).ConclusionsAngiopoietin-2 can be used as a biomarker of MetS and disease activity in RA patients. This could point to those RA patients at risk of developing CVDs.