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.     

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.     

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.     

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.     

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.     

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.     

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.     

Peroxisome proliferator-activated receptor gamma expression in peripheral monocytes from rheumatoid arthritis patients

Aim of the workTo study peroxisome proliferator activated receptor gamma (PPARγ) expression levels in the peripheral monocytes from rheumatoid arthritis (RA) patients and to clarify its relation with disease activity, functional disability and drug therapy.Patients and methodsThirty RA patients (Group 1) were divided into two subgroups: Group 1A: patients with moderate to high disease activity (n = 15); Group 1B: patients in remission or with low disease activity (n = 15). Thirty healthy volunteers were included as control group. Disease activity score in 28 joints (DAS-28) and Health Assessment Questionnaire (HAQ) were assessed in patients. PPARγ gene expression levels were assessed by real-time PCR in peripheral blood monocytes.ResultsThe mean fold increase in monocyte PPARγ expression levels was significantly higher (p < 0.001) in patients (6.87 ± 0.9) compared to control, being significantly higher (p < 0.001) in patients with remission or low activity (Group 1B) (7.6 ± 0.63) than patients with active RA (Group 1A) (6.13 ± 0.52). In RA patients, monocyte PPARγ expression levels showed significant negative correlations with morning stiffness durations, total joint count, visual analog scale for pain, DAS-28 and HAQ (p > 0.001) and with swelling joint count, erythrocyte sedimentation rate and platelet count (p < 0.05). A significant correlation was present with disease duration (p < 0.05) while there were no statistically significant correlations with any of Larsen score, C-reactive protein, hemoglobin concentrations, white blood cell count, rheumatoid factor or anti-cyclic citrullinated peptide titers (p > 0.05).ConclusionsOur findings support the role of PPARγ in the pathophysiology of RA and suggest that over-expression of PPARγ protein may have anti-rheumatic effects.     

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.     

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.     

Serum 25-hydroxy vitamin D levels in Egyptian patients with rheumatoid arthritis: Association with disease activity,functional disability and radiological damage

Aim of the workThe aim of this study was to examine vitamin D (VD) levels and its associations with disease activity, functional disability and radiological damage in Egyptian patients with RA.Patients and methodsThis study included 150 RA patients and 150 matched controls. All participants were not receiving VD supplements. Serum 25(OH)-D levels were measured in all participants. Serum 25(OH)-D levels at 30 and 20 ng/ml were the cut-off values for VD insufficiency and deficiency, respectively. Associations of 25(OH)-D levels with disease activity score associated with C-reactive protein (DAS-28-CRP), functional disability assessed by the Health Assessment Questionnaire (HAQ) and radiological damage as assessed by the modified Larsen method were considered.ResultsLow VD levels were frequent in RA patients (22 ± 9.2 ng/ml) compared to the control (28.7 ± 9.6 ng/ml) (p < 0.001); 42.7% had VD levels <20 ng/ml and was <30 ng/ml in 80.7%. RA patients with VD deficiency were older, more frequently females and had higher swollen joint count (SJC), tender joint count, visual analogue scale for pain and DAS28-CRP. Only SJC and DAS28-CRP remained significant following the multivariate analysis (p = 0.029, p = 0.007 respectively), while rheumatoid factor, anti-cyclic citrullinated peptide antibodies, medications used, HAQ and radiologic score had no association with VD levels.ConclusionsVitamin D insufficiency and deficiency are common among Egyptian RA patients and are associated with decreased sun exposure. VD deficiency was related to older age, female gender, swollen joint count and disease activity. Vitamin D levels had no relation with RA functional disability and radiological damage.     

Serum matrix metalloproteinase-3 in rheumatoid arthritis patients: Correlation with disease activity and joint destruction

Aim of the workThis study was designed to measure the serum level of matrix metalloproteinase-3 (MMP-3) in rheumatoid arthritis (RA) patients and its correlation with functional status, disease activity and joint damage.Patients and methodsThe study included 50 RA patients satisfying 2010 ACR/EULAR classification criteria recruited from Bani-Suef University Hospital and 20 controls. Functional disability was assessed according to Modified Health Assessment Questionnaire (MHAQ). Disease activity score in 28-joints (DAS28) and visual analogue scale (VAS) of pain were evaluated. Radiological joint damage was assessed by Van der Heijde-modified Sharp Score (vdHSS). Serum levels of MMP-3 were measured for all subjects.ResultsRA patients (44 females and 6 males) had a mean age of 46.36 ± 13.63 years and disease duration of 5.6 ± 4.75 years. Serum MMP-3 levels were higher in patients than in controls (46.78 ± 46.99 versus 1.98 ± 1.71 ng/ml respectively, p = 0.0001) and significantly correlated with erythrocyte sedimentation rate (p = 0.001) and were significantly higher in patients with positive C-reactive protein, rheumatoid factor and anti-cyclic citrullinated peptide (p = 0.0001, p = 0.009, p = 0.042, respectively). MMP-3 significantly correlated with DAS28 (p = 0.0001) and vdHSS (r = 0.78, p = 0.0001) and a significant difference was shown in those with erosions compared to those without (p = 0.001). Serum MMP-3 levels significantly correlated negatively with cumulative steroid dose (r = −0.2, p = 0.03) and were significantly higher in patients who never received disease-modifying antirheumatic drugs (p = 0.001). There were no significant relations of MMP-3 with age, MHAQ, VAS for pain.ConclusionThese results indicate that serum MMP-3 is a measurable, useful specific marker of disease activity and joint damage in RA patients.     

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.     

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.     

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.     

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.     

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.     

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.     

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.