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.     

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.     

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.     

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.     

Association of interferon-γ and its (+874 T/A) gene polymorphism with type 2 diabetes mellitus in rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) patients are at an increased risk of developing type-2 diabetes mellitus (T2DM) compared to the general population. Interferon-γ (IFN-γ) was found to have a role in both RA and T2DM.Aim of the workTo investigate the role of IFN-γ and its +874T/A gene polymorphism in the development of T2DM in RA patients.Patients and methodsIFN-γ level and its +874T/A gene polymorphism were investigated in 70 RA patients with T2DM and in 80 without, in addition to 150 healthy controls.ResultsThe level of IFN-γ was significantly higher in RA patients with (465 ± 64.4 pg/ml) and without (219 ± 50.3 pg/ml) T2DM compared to controls (110 ± 18 pg/ml) (p < 0.0001). IFN-γ +874T/A genotyping showed a significant increase in the frequency of AA genotype (42.9%) and a significant decrease in TT genotype (14.2%) in RA patients with T2DM compared to those without; similarly, the frequency of the T-allele was significantly lower (p < 0.05) and the A-allele increased (p < 0.05); however no significant differences in the genotypes distribution were found between non-diabetic RA patients and healthy controls. The TT-genotyped RA patients with (539.6 ± 4 pg/ml) and without (260 ± 59.6 pg/ml) diabetes had higher serum IFN-γ levels compared to other genotypes (p < 0.001), while in controls, no significant difference in IFN-γ levels according to genotype was observed.ConclusionsSerum IFN-γ and its gene polymorphism may play a role in the susceptibility of RA patients to T2DM. The homozygous genotypes AA and TT seem to be more commonly associated with diabetes in RA patients with special contribution of the A-allele.     

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.     

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.     

Anti-CCP hs (high sensitive) in Egyptian rheumatoid arthritis patients associated with chronic hepatitis C virus infection

Aim of the workThe objectives of this study were to evaluate the use of anti-cyclic citrullinated peptide high sensitive (anti-CCP hs) in the differentiation between rheumatoid arthritis (RA) and chronic hepatitis C virus (HCV) associated arthropathy and its correlation with disease activity and the degree of liver cirrhosis in RA associated with chronic HCV infection.Patients and methodThis study was carried out on 90 chronic HCV infection patients, 90 HCV negative RA patients and 90 HCV positive RA patients, in addition to 90 healthy volunteers. Hepatic assessment, rheumatological examination, quantitative HCV RNA test and abdominal ultrasonography were assessed in all HCV patients. Disease activity score (DAS-28) was assessed in RA patients. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibodies (ANA), cryoglobulins, rheumatoid factor (RF), anti-CCP3, anti-CCP hs test were assessed for all patients.ResultsThe higher frequency of anti-CCP hs was found in RA (HCV+ve) (88.9%) compared to RA (HCV-ve) (75.5%) and HCV patients (14.4%), its sensitivity in RA patients was 75.6% and specificity was 85.6%. In HCV patients anti-CCP hs significantly correlated with cryoglobulinemia and scoring for liver fibrosis (p < 0.001). In RA patients, anti-CCP hs significantly correlated with RF, anti-CCP3, DAS-28, ESR and CRP (p < 0.001).ConclusionsSerum anti-CCP hs is sensitive but not a specific marker for RA patients and cannot be used as a diagnostic marker to differentiate between RA and chronic HCV associated arthropathy, in addition it cannot be used as a marker of activity in RA especially when associated with HCV.     

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.     

Clinical significance of soluble-triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with rheumatoid arthritis

Aim of the workTo assess serum concentrations of triggering receptor expressed on myeloid cells-1 (sTREM-1) in rheumatoid arthritis (RA) patients, and correlate them with the main clinical, serological, radiological features and functional capacity of RA patients.Patients and methodsSera from 61 RA patients, and 30 healthy controls were assayed for sTREM-1 by Enzyme Linked Immunosorbant Assay. RA disease activity was assessed using 28-joint disease activity score (DAS-28). Assessment of patient’s functional capacity was done using modified health assessment questionnaire (mHAQ). Standardized X-rays were done to all RA participants and evaluated according to Larsen scoreResultsSerum levels of sTREM-1 were significantly higher in RA patients vs healthy controls (57.61 ± 28.87 and 43.72 ± 10.64 ng/ml; p = 0.027). These levels were higher in patients with severe disease activity (68.27 ± 36.14 ng/ml) than those with mild and moderate disease activity (43.50 ± 6.49 ng/ml and 47.52 ± 12.26 ng/ml, respectively; p = 0.008). On the contrary, no significant difference was found in levels of sTREM-1 in patients with extra-articular involvement or positive RF than those without. Levels of sTREM-1 showed a highly significant positive correlation with DAS-28 (P = 0.001), ESR (P = 0.02) and mHAQ (p = 0.003).There were no significant correlations between sTREM-1 level with age, disease duration, morning stiffness, nor radiological narrowing and erosion scores.ConclusionLevels of sTREM-1 were elevated in RA patients and correlated significantly with clinical and laboratory markers of disease activity as well as functional disability (as determined by mHAQ). To confirm our results we propose that larger scale, multicenter studies with longer evaluation periods are needed.     

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.     

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.     

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.     

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.     

Anti-mutated citrullinated vimentin antibodies in rheumatoid arthritis patients: Relation to disease activity and manifestations

Aim of the workTo evaluate the frequency of anti-mutated citrullinated vimentin antibodies (MCV) in rheumatoid arthritis (RA) patients and to correlate it with disease activity and various disease manifestations.Patients and methodsFifty RA patients were recruited from the rheumatology and rehabilitation outpatient clinic, Kasr Al-Aini. Thirty healthy subjects served as controls. All patients were subjected to full history taking and clinical examination including general and joint assessment. Disease activity was assessed by the disease activity score (DAS-28) and functional ability was evaluated by the Modified Health Assessment Questionnaire (MHAQ). Anti-MCV and anti-cyclic citrullinated peptide (anti-CCP) were assayed by ELISA in patients and controls. Plain X-ray was performed on the hands and wrists and Sharp score was used to assess the erosions and joint space narrowing.ResultsA highly significant elevation of serum anti-MCV in RA patients (135.82 ± 126.81 U/ml) compared to controls (13.63 ± 8.48 U/ml) (p < 0.0001) was found. Anti-MCV showed a sensitivity of 84% and specificity of 80%. There was a significant difference between anti-MCV positive and anti-MCV negative patients as regards MHAQ (1.07 ± 0.74 vs. 0.52 ± 0.37, p = 0.005) and Sharp erosion score (12.93 ± 23.55 vs. 4 ± 2.2, p = 0.02). Anti-CCP showed a sensitivity of 70% and specificity of 100%. There was a significant difference between the specificities of both markers (p = 0.03). There was no significant correlation of the anti-MCV with the clinical manifestations, MHAQ, DAS28 or Sharp score. Anti-MCV significantly correlated with anti-CCP (p < 0.0001).ConclusionAnti-MCV test has a significant association with the functional disability and radiologic progression in RA and could be considered as a promising biomarker.     

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.     

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.     

Anti-Carbamylated Protein Antibodies,Tumour Necrosis Factor Alpha and Insulin Resistance in Egyptian Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus

BackgroundRheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are autoimmune diseases. Premature atherosclerosis and cardiovascular diseases are two of the most important complications of these diseases. Anti-carbamylated protein antibody (Anti-carP Ab) is one of the antibodies which was studied in RA and SLE. In our study, we studied the relation between anti-carP Ab, disease activity and insulin resistance in RA and SLE patients.Methods90Patients with SLE and RA were enrolled and subjected to history taking, clinical examination and assessment of disease activity using SLE disease activity index 2000 (SLEDAI-2K) scoring for SLE patients and disease activity score 28 (DAS28-ESR) for RA patients. Samples were examined for complete blood count (CBC), creatinine, inflammatory markers, Tumour necrosis factor alpha (TNF alpha), fasting insulin, fasting blood sugar (FBS), lipid profile and anti-carPAb. HOMA-IR (homeostasis model assessment for insulin resistance) was calculated.ResultsPatients with RA and SLE showed higher levels of anti-carPAb in comparison with healthy subjects (8.25 ng/ml for RA, 7 ng/ml for SLE and 0.6 ng/ml for healthy subjects with p value <0.001). There was a positive correlation between anti-carPAb and disease activity of RA (p value <0.001) and a positive correlation between anti-carPAb and TNF alpha in RA. In SLE, there was no correlation of anti-carP Ab with disease activity while, HOMA-IR showed a positive correlation with nephritis (p value 0.04).ConclusionAnti-carP antibody is a marker of disease activity in RA patients and has high specificity for both RA and SLE detection.     

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.