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.     

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.     

Levels of plasma cell-free DNA and its correlation with disease activity in rheumatoid arthritis and systemic lupus erythematosus patients

BackgroundCell free deoxyribonucleic acid (cf-DNA) is now emerging as a useful tool for non-invasive diagnostic methods related to a wide range of clinical conditions including autoimmune diseases.Aim of the workTo estimate the concentration of plasma cf-DNA in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients compared with healthy subjects and to correlate the results with clinical and laboratory parameters of disease activity.Patients and methodsThe study included 30 RA patients, 35 SLE patients and 25 matched control. Plasma cf-DNA was estimated by real-time quantitative PCR. Disease activity parameters for each disease were assessed; Disease Activity Score-28 (DAS28) was used for RA and SLE disease activity index 2000 (SLEDAI-2K) for SLE patients.ResultsThe RA patients (F:M 4:1) had a mean age of 36.8 ± 9.6 years and disease duration of 8.3 ± 1.1 years while the SLE patients (F:M 7.75:1) had a mean age of 35.6 ± 8.8 years and disease duration of 8.1 ± 0.87 years. There was a highly significant increase in the cf-DNA level in SLE patients (17.33 ± 2.4 ng/ml) and RA patients (11.15 ± 2.3 ng/ml) compared to the level in the control (4.15 ± 1.4 ng/ml) (p = 0.0005). The cf-DNA significantly correlated with the erythrocyte sedimentation rate (ESR) (p = 0.04), C-reactive protein (p = 0.04) and the DAS28 (p = 0.005) in the RA patients and with the ESR (p = 0.03), anti-ds-DNA (p = 0.008), complement-4 (p = 0.04) and SLEDAI-2K (p = 0.002).ConclusionThe increased cf-DNA implicates a possible role in the pathogenesis of both RA and SLE and appears to be a useful marker of disease activity in addition to other laboratory tests.     

Fatigue in rheumatoid arthritis and its relation to interleukin-6 serum level

Patients and methodsThe study included 30 patients with RA diagnosed according to the 2010 ACR-EULAR classification criteria for RA and 15 healthy controls. Patients were included if they were above 18 years and fulfilled a score ?6 over 10 of the 2010 ACR-EULAR classification criteria for RA. Disease activity was assessed using 28 joint disease activity score (DAS28), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP). Fatigue was assessed with the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ) and serum IL-6 level was measured in patients and controls.ResultsThe BRAF-MDQ was significantly higher among patients (mean = 50.6 ± 15.2) than controls (mean = 7.8 ± 3.7) (p < 0.001). Patients’ mean IL-6 serum level was 35.05 ± 21.23 pg/ml and 4.72 ± 3.09 pg/ml among control subjects (p < 0.001). DAS 28 ranged between 4.33 and 7.67, mean 1st hour ESR was 43.57 mm and CRP was positive in 76.7% of patients. Significant correlations were found between BRAF-MDQ score and serum IL-6 level (r = 0.947, p < 0.001), ESR (r = 0.509, p < 0.001) as well as CRP positivity (r = 0.411, p = 0.005) in RA patients. Serum IL-6 level correlated with ESR (r = 0.463, p < 0.001) and CRP (r = 0.376, p = 0.01) among patients.ConclusionFatigue is a common symptom and scores higher among RA patients than healthy controls and should be measured in all RA patients with simple fatigue questionnaires matching with different cultures. Fatigue becomes more prominent as serum IL-6 level increases independently of the disease duration and activity.     

HLA-DRB1 alleles in Egyptian rheumatoid arthritis patients: Relations to anti-cyclic citrullinated peptide antibodies,disease activity and severity

BackgroundHuman leukocyte antigen HLA-DRB1 alleles encoding a common amino acid sequence called shared epitope in the third hypervariable region of DRB1 molecule have been identified as risk alleles for rheumatoid arthritis (RA).Aim of the workThe aim was to study HLA-DRB1 01, 04 and 10 alleles in Egyptian RA patients and determine their relation with anticyclic citrullinated peptide (anti-CCP) antibody level, disease activity, clinical and radiological severity.Patients and methodsThe study involved 40 RA patients and 20 control. Simplified disease activity index (SDAI) was calculated, clinical severity was assessed using the mechanical joint score (MJS) and radiological severity evaluated using the simple erosion narrowing score (SENS). HLA-DRB1 genotyping and anti-CCP antibodies were detected.ResultsThe mean patients’ age was 41.6 ± 12.7 years and disease duration 8.9 ± 7.7 years. The frequency of HLA DRB1 01, 04 and 10 in patients was 42.5%, 60% and 25% respectively. Of them 04 was significantly higher than in controls (p = 0.013) and was associated with anti-CCP positive cases (p = 0.0008) while the absence of HLA-DRB1 alleles was significantly associated with negative anti-CCP negative RA (p = 0.0008). There were significant associations between HLA-DRB1 01 and 04 with SDAI (p = 0.0002 and p = 0.005, respectively); between HLA-DRB1 04 and 10 with SENS (p = 0.002 and p = 0.001 respectively) and between HLA-DRB1 01, 04 and 10 with MJS (p = 0.02, p = 0.03 and p = 0.02, respectively).ConclusionHLA-DRB1 04 is associated with RA in Egyptian patients and is strongly associated in the production of elevated titers of anti-CCP antibodies which contribute to the development, severity and activity of the disease.     

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.     

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in rheumatoid arthritis patients: Correlation with serum osteopontin levels and disease activity

BackgroundRheumatoid arthritis (RA) is a systemic, chronic inflammatory disease with genetic predisposition. Osteopontin (OPN) is overexpressed in RA and plays a key role in the perpetuation of synovitis. Not all RA patients show the same level of response to methotrexate (MTX) suggesting genetic variations in the drug-metabolizing enzymes.Aim of the workTo detect methylene-tetra-hydrofolate reductase (MTHFR) 677C/T and 1298A/C gene polymorphisms in RA patients treated with MTX and to investigate the relationship with serum OPN levels and disease activity.Patients and methods62 RA patients and 21 healthy controls were included. Serum OPN was measured using ELISA. Genotyping of MTHFR gene was carried out by polymerase chain reaction-restriction fragment length polymorphism. Disease activity score in 28 joints (DAS28) and the modified health assessment questionnaire (MHAQ) were assessed.ResultsThe patients’ age was 42.7 ± 12.7 years, F:M (4.6:1) and a disease duration of 5.7 ± 4.6 years. Their DAS28 was 4.1 ± 1.6 and the MHAQ (median 1; range 0–2.3). Serum OPN levels in RA patients (median 8.8; range 4–44.5 ng/ml) were significantly higher than in control (5.6; 2.1–10.9) (p = 0.002). In RA patients, serum OPN significantly correlated with the duration of morning stiffness (p = 0.009), ESR (p < 0.0001) and DAS28 (p < 0.0001). MTHFR (677C>T) polymorphisms significantly correlated with MHAQ (p = 0.012) while (1298A>C) polymorphisms significantly correlated with tender joint count (p = 0.04). OPN levels were higher among patients with MTHFR (1298A/C) AC genotype (8.9; 4.1–33.9 ng/ml), while in those with (677C>T) polymorphisms it was higher among those with CT genotype (8.9; 4.1–44.5).ConclusionSerum OPN level relates with the degree of rheumatoid activity.     

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.     

IL-17 is a key cytokine correlating with disease activity and clinical presentation of systemic lupus erythematosus

AimsTo determine the role of IL-17 cytokine in systemic lupus erythematosus (SLE) patients and its association with clinical presentation of the disease and disease activity.Methods72 SLE patients and 70 healthy age and sex matched controls were included in the study. SLE disease activity was assessed in all patients with SLE disease activity index (SLEDAI-2K) scores. Plasma levels of IL-6, and IL-17 were measured by enzyme-linked immunosorbent assay and correlated their levels with clinical manifestations of the disease and SLEDAI-2K.ResultsPlasma levels of IL-6 and IL-17 were significantly elevated in SLE patients than in control subjects (13.98 ± 6.95 versus 7.47 ± 1.23 pg/mL) and (19.47 ± 10.21 versus 9.93 ± 1.89 pg/mL), respectively. IL-6 and IL-17 were positively correlated with SLEDAI-2K scores (r = 0.684 at P < 0.001, r = 0.322 at P = 0.006), and lupus nephritis (r = 0.364 at P = 0.002, r = 0.474 at P < 0.001) respectively; similarly, the IL-17/IL-6 ratio was positively correlated with SLEDAI-2K (r = 0.243 at P = 0.039). Also, the level of both cytokines was positively correlated to each other during periods of disease activity (r = 0.755, P < 0.001) as well as during remission (r = 0.384, P = 0.040).ConclusionOver-expression of IL-17 correlates with disease activity of SLE. A longitudinal study in a larger cohort of SLE patients can help validate the results.     

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.     

T helper type cytokines in sepsis: time-shared variance and correlation with organ dysfunction and hospital mortality

ObjectiveWe evaluated the kinetics of cytokines belonging to the T helper1 (Th1), Th2, and Th17 profiles in septic patients, and their correlations with organ dysfunction and hospital mortality.MethodsThis was a prospective observational study in a cohort of septic patients admitted to the intensive care units (ICU) of three Brazilian general hospitals. A total of 104 septic patients and 53 health volunteers (controls) were included. Plasma samples were collected within the first 48 h of organ dysfunction or septic shock (0D), after seven (D7) and 14 days (D14) of follow-up. The following cytokines were measured by flow cytometry: Interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-10, IL-12/23p40, IL-17, IL-21, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF).ResultsIL-6, IL-8, G-CSF and IL-10 concentrations were higher in septic patients than in controls (p < 0.001), while IL-12/23p40 presented higher levels in the controls (p = 0.003). IL-6, IL-8 and IL-17 correlated with Sequential [Sepsis-related] Organ Failure Assessment (SOFA) D0, D1 and D3 (except for IL-6 at D0). IL-8 was associated with renal and cardiovascular dysfunction. In a mixed model analysis, IL-10 estimated means were lower in survivors than in deceased (p = 0.014), while IL-21 had an estimated mean of 195.8 pg/mL for survivors and 98.5 for deceased (p = 0.03). Cytokines were grouped in four factors according to their kinetics over the three dosages (D0, D7, D14). Group 1 encompassed IL-6, IL-8, IL-10, IL-1β, and G-CSF while Group 3 encompassed IL-17 and IL-12/23p40. Both correlated with SOFA (D0) (p = 0.039 and p = 0.003, respectively). IL-21 (Group 4) was higher in those who survived. IL-2, TNF-α and GM-CSF (Group 2) showed no correlation with outcomes.ConclusionInflammatory and anti-inflammatory cytokines shared co-variance in septic patients and were related to organ dysfunctions and hospital mortality.     

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.     

CD14++CD16+ monocyte subset expansion in rheumatoid arthritis patients: Relation to disease activity and interleukin-17

Aim of the workMonocytes are divided into three major subsets based on the expression of the cluster of differentiation CD14 and CD16. The aim of this work was to determine which of the CD16⁺ monocyte subpopulations is expanded in rheumatoid arthritis (RA) and its association with disease activity and interleukin-17 (IL17) levels.Patients and methodsFifty-three RA patients and 20 controls were enrolled in this study. Flow cytometry was performed to detect monocyte subsets and IL17 was measured by ELISA. Disease activity score (DAS28) was assessed.ResultsCD14⁺⁺CD16⁺ monocyte percentage was significantly higher in long standing RA patients compared with early patients and controls (p < 0.01, p < 0.001 respectively). It was significantly higher in patients with RA disease activity and remission compared with the controls (p < 0.001, p < 0.01 respectively). It was not significantly associated with resistance to disease modifying antirheumatic drugs (DMARDs), C-reactive protein, rheumatoid factor and anti-CCP positivity (p > 0.05). It significantly correlated with IL17 (p < 0.002). CD14⁺CD16⁺ monocyte percentage was not significantly correlated with any of the above parameters. IL17 level was significantly higher in patients with early and long standing RA compared to controls (p < 0.01, p < 0.001 respectively). IL17 was higher in RA patients with active disease compared to those in remission and controls (p < 0.01, p < 0.001 respectively). It was higher in RA patients resistant to DMARDs than in responding patients (p < 0.017).ConclusionCD14⁺⁺CD16⁺ monocyte subpopulation was expanded in long standing RA and was correlated with IL17 levels indicating its potential pathogenic importance in RA and may represent an attractive target for future therapeutic interventions.     

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.     

Sclerostin as an innovative insight towards understanding Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation leading to cartilage and local bone erosion. Sclerostin is a protein that in humans has been identified as an inhibitor of the pathway and leads to decreased bone formation.Aim of the workThis study aimed to investigate the level of serum sclerostin in RA patients, its association with inflammatory profile and its relation to disease activity and severity.Patients and methodsThirty-one Egyptian RA patients (28 females, 3 men) participated in this study. Their median age was 40 years. Disease activity score was assessed by the disease activity score (DAS28) and the functional status by the modified health assessment questionnaire (MHAQ). Ten matched controls were also included. Radiological severity was assessed according to the Larsen score. Serum sclerostin was measured.ResultsMedian serum sclerostin in RA patients was 2000 ng/dl (800–3300 ng/dl) which was significantly higher than in controls [210 ng/dl (150–2859)] (Z = −4.47, p < 0.001). Sclerostin significantly negatively correlated with C-reactive protein and DAS28 (p = 0.014 and p = 0.02 respectively) and positively correlated with the Larsen score and total joint count (p = 0.03 and p = 0.02 respectively). At serum level 267 ng/dl sclerostin has sensitivity of 96.8% to diagnose RA and a positive predictive value of 96.6%.ConclusionSerum sclerostin was significantly higher in RA patients than controls and correlated with disease activity and severity which highly suggests that it may play a role in the pathogenesis of RA making it a valuable new marker of monitoring the disease progress and prognosis.     

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.     

Autoantibodies to extractable nuclear antigens (ENAs) pattern in rheumatoid arthritis patients: Relevance and clinical implications

ObjectivesTo study the frequency of different autoantibodies to extractable nuclear antigens (ENAs) in rheumatoid arthritis (RA) patients and to correlate findings with clinical manifestations, disease activity and radiological damage.MethodsA total of 230 RA patients were included and 75 healthy controls. In all patients rheumatological assessment was done and routine laboratory investigations and immune profile were performed in both patients and controls, including: RF, ACPA, ANA and anti-ENAs (Ro/SSA, La/SSB, U1-RNP, anti-Jo-1 and anti-Sm). Radiological damage was scored using Sharp/van der Heijde, and disease activity was evaluated by DAS28-ESR and DAS28-CRP.ResultsRF was positive in 101 (43.9%), ACPA in 220 (95.7%), ANA in 58 (25.2%), anti Ro in 31 (13.5%), anti-La in 10 (4.3%), anti-Jo1 in 5 (2.2%) and anti-RNP in 2 (0.9%). Anti-Ro/SSA positively correlated with sicca symptoms (p = .02), RF titer (p < .001), ANA (p < .001), DAS28-ESR (p = .026), and DAS28-CRP (p = .003). Anti-La antibodies correlated positively with SJC (p = .001), TJC (p = .001), ANA (p < .001), DAS-28 ESR (p = .007). Anti-Jo-1 correlated positively with interstitial lung disease (ILD) (p ≤ .001), RF titer (p = .037) and ANA (p ≤ .001). Anti-RNP antibodies correlated positively with disease duration (p ≤ .001), ACPA titer (p ≤ .001) and ANA (p = .014). In the controls ANA was positive in two (2.7%), anti-Ro in three (4%), and none of the controls tested positive for other autoantibodies.ConclusionsIn RA patients, positive ANA is frequent and positively associated with anti-Ro, anti-La and anti-Jo1 autoantibodies. Screening for autoantibodies against other anti-ENAs seems mandatory in RA patients especially when ANA is positive. RA cases with positive Anti-Jo-1 may develop anti synthetase syndrome and ILD.     

Alteraciones temporomandibulares y odontológicas en pacientes con artritis reumatoide

ObjectiveTo characterize the orofacial abnormalities in patients with rheumatoid arthritis (RA) and compare them with those in a reference population.MethodsThe study included 30 RA patients and 30 consecutive patients in an odontology clinic in whom RA was ruled out. Patients underwent a clinical dental examination which included: 1) clinical and radiographic abnormalities of the temporomandibular joint; 2) biomechanical craniocervical analysis; 3) state of dentition and treatment needs; 4) periodontal status; 5) oral hygiene status; and 6) facial pain, which was compared among study groups. In addition, the association between the variables studied was determined through correlation tests.ResultsPatients with RA showed a higher prevalence of temporomandibular abnormalities, both clinical (100.0% vs. 60.0%, P < .001) and radiographic, including erosions (50.0% vs. 16.0%, P = .010), compared with individuals in the control group. Likewise, patients with RA had a greater number of missing teeth (6.9 ± 5.7 vs. 3.0 ± 2.0, P = .001), more caries (13.4 ± 5.4 vs. 4.9 ± 6.5, P = .001), periodontitis (1.3 ± 0.9 vs. 0.8 ± 0.8, P = .015), poorer oral hygiene (43.3% vs. 13.3%, P = .005) and greater facial pain (66.7% vs. 20.0%, P < .001). The cephalometric analysis of Rocabado showed differences in the craniocervical angle and hyoid triangle between RA and controls. Significant correlations were obtained between oral and temporomandibular abnormalities.ConclusionsPatients with RA showed a greater orofacial deterioration, which reflects the importance of multidisciplinary care, including periodic dental examination.     

Interleukin-27 and its relation to disease parameters in SLE patients

IntroductionIL-27 exerts profound anti-inflammatory effects in several experimental autoimmune models, suggesting that it may be therapeutically relevant in SLE.Aim of the workTo evaluate IL-27 level in SLE patients and its association to clinical manifestations, disease activity parameters and management strategy.Patients and methodsWe studied 80 SLE patients and 50 controls in a cross sectional study. Demographic, clinical and serological data were evaluated. Systemic lupus erythematosus disease activity index (SLEDAI) and Systemic Lupus International Collaboration Clinics/ACR damage index (SLICC) were assessed. Serum IL-27 was measured by ELISA.ResultsThere was statistically significant difference in IL-27 level in SLE patients and healthy controls (9.7 ± 21.9 pg/ml vs 20.2 ± 47.3 pg/ml in SLE vs controls, respectively) (p = 0.04), also it was found that IL-27 level was statistically significantly lower in SLE patients with lupus nephritis (p = 0.02) and cerebritis (p = 0.03). Interleukin 27 level had a statistically significant negative correlation with the cumulative dose of hydroxychloroquine and azathioprine (r = ?0.3, p = 0.03 and r = ?0.3 and p = 0.04, respectively).ConclusionIL-27 has anti-inflammatory effect in SLE patients especially those without nephritis or cerebritis and can be therapeutically relevant in SLE. To confirm our results we propose larger scale, multicentre studies with longer evaluation periods.