Tumor necrosis factor-alpha and Interleukin-10 gene promoter polymorphisms in Turkish rheumatoid arthritis patients

Tumor necrosis factor and interleukin 10 have been implicated in the pathogenesis of rheumatoid arthritis (RA). Certain single-nucleotide polymorphisms (SNPs) within the promoter region of the IL-10 and TNF genes have been associated with altered levels of circulating IL10 and TNF. We aimed to explore the association of IL-10 and TNF-alpha polymorphisms in Turkish RA patients. We analyzed the association of TNF-alpha (-308G/A, -238G/A, -376G/A) and IL10 (-1082G/A, -819C/T, -592C/A) polymorphisms in 98 Turkish patients with rheumatoid arthritis and 122 healthy subjects using ARMS-PCR. The correlation of these findings with RF positivity and erosive disease in RA patients was also sought. A significant association was found between having RA and -1082 G allele (p = 0.008; OR = 1.44, 95% CI 1.11-1.86). There was no association between RA and -819C/T polymorphism. Significant differences were observed in IL10 GCC and ACC haplotypes distribution between RA and control subjects (p = 0.006; OR = 1.46, 95% CI 1.13-1.89 and p = 0.011; OR = 1.43, 95% CI 1.09-1.88, respectively). No statistically significant association was found between TNF-alpha 308G/A, -238G/A, -376G/A polymorphisms and RA. No significant association was found between RF positivity and erosive disease and TNF-alpha, IL10 gene polymorphisms. In addition, when combined genotypes were analyzed, no significant difference was found between RA patients and healthy controls. Our findings suggest that IL-10 1082 G/A polymorphism or GCC, ACC haplotypes may be associated with RA in Turkish patients.     

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.     

Effects of glucosamine administration on patients with rheumatoid arthritis

The purpose of this study was to examine whether glucosamine has an antirheumatic effect in a randomized placebo-controlled study.The subjects were 51 rheumatoid arthritis (RA) patients: 25 patients in the glucosamine group and 26 patients in the placebo group. Glucosamine hydrochloride at a daily dose of 1,500 mg and placebo, respectively, were administered for 12 weeks along with conventional medication.While significant improvement was not found in joint counts and in the rate of ACR20 responders, the face scale and a visual analogue scale pain were significantly in favor of the glucosamine group. ESR and CRP levels did not change, but serum MMP-3 levels decreased in the glucosamine group. Results of the patients’ self-evaluations and the physicians’ global evaluations indicated that the glucosamine treatment produced noticeable improvements in symptoms.Although glucosamine administration had no antirheumatic effect evaluated by conventional measures, it seemed to have some symptomatic effects on RA.     

Elevation of serum matrix metalloproteinase-3 as a predictive marker for the long-term disability of rheumatoid arthritis patients in a prospective observational cohort IORRA

Matrix metalloproteinases (MMPs) are the proteases responsible for the destruction of cartilage in rheumatoid arthritis (RA) patients; especially the role of MMP-3 in RA has been highlighted from both pathophysiological studies and clinical studies. However, the role of serum MMP-3 in a large observational cohort of RA patients has not been well demonstrated. In a large observational cohort of RA patients in our Institute (IORRA, October 2000–October 2005, n = 3834–5049/phase), disease activity and functional status were routinely assessed biannually. In October 2001, serum MMP-3 was measured in 1265 patients in this cohort, and the data of these patients in the subsequent 4 years were analyzed. The functional status of disability was assessed by JHAQ, the verified Japanese version of HAQ. A cut-off point of 121.0 ng/ml (men) and 59.7 ng/ml (women) was used for MMP-3 positive/negative categorization. The baseline data of these 1265 patients include 81.5% women, mean age 57.9, mean duration 11.1 years, and 71.7% of patients were rheumatoid factor (RF)-positive. Serum MMP-3 levels at the baseline (195.1 + 227.9 ng/ml) were weakly correlated with C-reactive protein (CRP), but qualitative elevation of serum MMP-3 using cut-off points correlated significantly with corticosteroids use, DAS28, CRP, erythrocyte sedimentation rate, JHAQ, or other markers for the disease activity, but not with age or the disease duration. Thus, elevation of serum MMP-3 level represents the disease activity of RA patients regardless of age or the disease duration. In the longitudinal analysis, the slope of JHAQ progression in patients with MMP-3 positive and RF positive, MMP-3 positive and RF negative, MMP-3 negative and RF positive and MMP-3 negative and RF negative were 0.0179, 0.0162, 0.0156, and 0.0119, respectively, indicating that JHAQ increased most progressively in RA patients with MMP-3 positive and RF positive patients, although statistically apparent differences were not identified. In 502 female patients without talking corticosteroid, patients with MMP-3 positive and RF positive were statistically more progressive in the disability than patients with MMP-3 negative and RF negative. In conclusion, elevation of serum MMP-3 in RA patients is an indicator of inflammation, and together with RF, elevation of serum MMP-3 is a predictive marker for the progression in disability especially in female patients without corticosteroid.     

Elevation of serum matrix metalloproteinase-3 as a predictive marker for the long-term disability of rheumatoid arthritis patients in a prospective observational cohort IORRA

Abstract

Matrix metalloproteinases (MMPs) are the proteases responsible for the destruction of cartilage in rheumatoid arthritis (RA) patients; especially the role of MMP-3 in RA has been highlighted from both pathophysiological studies and clinical studies. However, the role of serum MMP-3 in a large observational cohort of RA patients has not been well demonstrated. In a large observational cohort of RA patients in our Institute (IORRA, October 2000–October 2005, n = 3834–5049/phase), disease activity and functional status were routinely assessed biannually. In October 2001, serum MMP-3 was measured in 1265 patients in this cohort, and the data of these patients in the subsequent 4 years were analyzed. The functional status of disability was assessed by JHAQ, the verified Japanese version of HAQ. A cut-off point of 121.0?ng/ml (men) and 59.7?ng/ml (women) was used for MMP-3 positive/negative categorization. The baseline data of these 1265 patients include 81.5% women, mean age 57.9, mean duration 11.1 years, and 71.7% of patients were rheumatoid factor (RF)-positive. Serum MMP-3 levels at the baseline (195.1 + 227.9?ng/ml) were weakly correlated with C-reactive protein (CRP), but qualitative elevation of serum MMP-3 using cut-off points correlated significantly with corticosteroids use, DAS28, CRP, erythrocyte sedimentation rate, JHAQ, or other markers for the disease activity, but not with age or the disease duration. Thus, elevation of serum MMP-3 level represents the disease activity of RA patients regardless of age or the disease duration. In the longitudinal analysis, the slope of JHAQ progression in patients with MMP-3 positive and RF positive, MMP-3 positive and RF negative, MMP-3 negative and RF positive and MMP-3 negative and RF negative were 0.0179, 0.0162, 0.0156, and 0.0119, respectively, indicating that JHAQ increased most progressively in RA patients with MMP-3 positive and RF positive patients, although statistically apparent differences were not identified. In 502 female patients without talking corticosteroid, patients with MMP-3 positive and RF positive were statistically more progressive in the disability than patients with MMP-3 negative and RF negative. In conclusion, elevation of serum MMP-3 in RA patients is an indicator of inflammation, and together with RF, elevation of serum MMP-3 is a predictive marker for the progression in disability especially in female patients without corticosteroid.     

Steroid therapy and renal dysfunction are independently associated with serum levels of matrix metalloproteinase-3 in patients with rheumatoid arthritis

Objective: This study aimed to evaluate whether the level of serum matrix metalloproteinase-3 (MMP-3), a marker of synovium inflammation, is affected by clinical characteristics of patients in rheumatoid arthritis (RA) patients.

Methods: We analyzed data from 1087 female patients with RA. Pearson’s correlation coefficients were calculated to explore associations between variables. Stepwise multiple linear regression analysis was performed to evaluate patient background variables that could potentially affect serum MMP-3 levels.

Results: Serum MMP-3 was moderately correlated with C-reactive protein (CRP) (r: 0.478). Factors that independently influenced serum MMP-3 levels were CRP (β: 0.450), prednisolone (PSL) use (β: 0.100), estimated glomerular filtration rate (eGFR) (β: ?0.085), swollen joint count assessed on 28 joints (β: 0.072), and body mass index (β: ?0.061) in female patients with RA. In RA patients with PSL use, factors that independently influenced serum MMP-3 levels were CRP (β: 0.480), eGFR (β: ?0.175), and PSL dose (β: 0.171).

Conclusions: Our findings suggest that steroid therapy and renal dysfunction affect serum MMP-3 levels in patients with RA.     

Etanercept reduces the serum levels of interleukin-23 and macrophage inflammatory protein-3 alpha in patients with rheumatoid arthritis

The purpose of this study was to analyze the effect of the soluble TNF-α receptor etanercept on the serum levels of IL-16, IL-17, IL-23, and macrophage inflammatory protein-3α (MIP-3α) in rheumatoid arthritis (RA) patients. Twenty-two patients with RA were administered etanercept once or twice a week for more than 6 months, and we evaluated clinical and laboratory parameters and serum levels of IL-16, IL-17, IL-23, and MIP-3α at the baseline and at 3 and 6 months. Additionally, the production of IL-23 and MIP-3α of cultured synovial cells stimulated with TNF-α from RA patients was determined by ELISA. We also used ELISA kits to determine synovial fluid (SF) levels of IL-17, IL-23, and MIP-3α in patients with RA, osteoarthritis (OA), pseudogouty arthritis (PGA), and gouty arthritis (GA). A significant decrease in serum levels of IL-23 and MIP-3α was observed at 3 and 6 months after initial treatment of etanercept. TNF-α induced MIP-3α but not IL-23 production in cultured synovial cells from RA patients. SF levels of IL-17, IL-23, and MIP-3α in RA patients showed significantly higher levels than those of OA, PGA, and GA patients. This study demonstrated that the reduction of IL-23 and MIP-3α production in RA patients was a newly determined function of etanercept     

Weighting with the Lansbury articular index improves the correlation of ultrasound score with serum matrix metalloproteinase-3 level in rheumatoid arthritis patients

Abstract

Objective. To determine whether weighting improves the correlation of ultrasound (US) score with serum matrix metalloproteinase-3 (MMP-3) level in rheumatoid arthritis (RA).

Methods. As ultrasound examination was performed on 100 RA patients, and the severity of synovial effusion and synovial hypertrophy and the blood flow were semi-quantitatively graded from 0 to 3 by using the gray-scale (GS) and power Doppler (PD) modes. We then calculated the sums of the scores of the 28 joints of each patient in the 2 modes, that is, the GS28 and PD28 scores, as well as the respective scores weighted using the Lansbury articular index (LAI, shoulder and elbow, × 12; wrist, × 8; and knee, × 24)—Lans GS28 and Lans PD28 scores.

Result. The Lans PD28 score showed a higher correlation with MMP-3 (r = 0.591; 95% confidence interval, 0.446–0.705, p < 0.0001) than the existing measures. The scores of the large joints—the knee, shoulder, and elbow—correlated well with the serum MMP-3 level.

Conclusion. Weighting with the LAI can improve the correlation of US findings with serum MMP-3 level. Bidirectional approach based on both serum MMP-3 level and US scores can further improve the assessment of disease activity in RA patients.     

Synovial fluid and serum levels of soluble interleukin-6 receptor in patients with rheumatoid arthritis

Our objective was to measure both synovial fluid (SF) and serum levels of soluble interleukin-6 receptor (sIL-6R) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA), and to investigate the amounts of sIL-6R protein produced by cultured synovial cells, chondrocytes and mononuclear cells (MNCs). We measured levels of sIL-6R using a sensitive and specific enzyme-linked immunosorbent assay. Synovial cells, chondrocytes and MNCs were cultured, and the supernatants were also measured for sIL-6R. SF levels of sIL-6R in RA were significantly higher than those in OA. SF levels of sIL-6R significantly correlated with SF levels of IL-6 in RA. The serum level of sIL-6R was approximately 3-fold higher than the SF level of sIL-6R. sIL-6R protein was not detected in the supernatants of synovial cells and chondrocytes. As compared to the SF levels of sIL-6R, a small amount of sIL-6R protein was produced by SF MNCs. The above findings suggest that increased amounts of sIL-6R form IL-6-sIL-6R complexes which mediate IL-6 function in RA joints and that SF sIL-6R protein might be not only produced in affected joints, but also supplied from the serum.     

Synovial fluid and serum levels of soluble interleukin-6 receptor in patients with rheumatoid arthritis

Abstract

Our objective was to measure both synovial fluid (SF) and serum levels of soluble interleukin-6 receptor (sIL-6R) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA), and to investigate the amounts of sIL-6R protein produced by cultured synovial cells, chondrocytes and mononuclear cells (MNCs). We measured levels of sIL-6R using a sensitive and specific enzyme-linked immunosorbent assay. Synovial cells, chondrocytes and MNCs were cultured, and the supernatants were also measured for sIL-6R. SF levels of sIL-6R in RA were significantly higher than those in OA. SF levels of sIL-6R significantly correlated with SF levels of IL-6 in RA. The serum level of sIL-6R was approximately 3-fold higher than the SF level of sIL-6R. sIL-6R protein was not detected in the supernatants of synovial cells and chondrocytes. As compared to the SF levels of sIL-6R, a small amount of sIL-6R protein was produced by SF MNCs. The above findings suggest that increased amounts of sIL-6R form IL-6-sIL-6R complexes which mediate IL-6 function in RA joints and that SF sIL-6R protein might be not only produced in affected joints, but also supplied from the serum.     

Galectin-3 and interleukin-7 as potential serologic markers in rheumatoid arthritis patients

Aim of the workTo assess the level of serum galectin-3 and interleukin-7 (Il-7) in rheumatoid arthritis (RA) patients and to study their association with disease activity as well as other disease parameters.Patients and methodsSerum samples from 66 RA patients and 20 matched controls were tested for galectin-3 and IL-7 using enzyme-linked immunosorbent assay (ELISA). Disease activity was assessed using disease activity score (DAS28).ResultsThe mean age of the patients was 46.6 ± 12.02 years, mean disease duration was 7.5 ± 7.6 years and they were 61 females and 5 males. The mean DAS28 of the patients was 4.72 ± 1.77. Serum galectin-3 and IL-7 were higher in RA patients (7.7 ± 5.7 ng/ml and 9.03 ± 5.97 pg/ml) than the control (1.5 ± 0.8 ng/ml and 1.6 ± 1.1 pg/ml) (p < 0.001). Serum galectin-3 and IL-7 significantly correlated with age (r = 0.27, p = 0.03 and r = 25, p = 0.04), DAS28 (r = 0.64, p < 0.001 and r = 39, p = 0.001), as well as to each other (r = 0.48, p < 0.001). Serum galectin-3 significantly correlated with ESR (r = 0.29, p = 0.018) and significantly higher in those with fever (p = 0.017). At a cutoff of 2.94 ng/ml, serum galectin-3 showed 84.8% sensitivity and 100% specificity (p < 0.001) and at 2.71 pg/ml, serum IL7 showed a sensitivity of 92.4% and a specificity of 95% (p < 0.001) to diagnose RA.ConclusionSerum galectin-3 and IL-7 were higher in patients than in controls and were increased with high disease activity making them promising biomarkers for RA. Both of them showed high diagnostic power for RA. This may provide further understanding of RA pathogenesis and suggest new therapeutic interventions.     

Diagnostic potential of interleukin-40 (IL-40) in rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is the most common type of inflammatory arthritis. Newly emerging evidence has highlighted the role of B-cell produced cytokines in the development and progression of RA. Specifically, the expression of IL-40 has been shown to be significantly increased in affected patients.Patients and methodsThe study included 66 patients attending Rheumatology Unit, Baghdad Teaching Hospital and 66 matched controls. C-reactive protein (CRP), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were measured. Disease activity score (DAS28) was assessed. Serum IL-40 levels were assessed using an enzyme-linked immunosorbent assay (ELISA).ResultsThe mean ages of patients were 46.5 ± 10.2 years (23–68 years) and were 55 females and 11 males (F:M 5:1). 4 were smokers. Positivity of CRP, RF and anti-CCP were 75.8 %, 65.2 % and 62.2 % respectively. Steroids were received by 21.2 %, methotrexate by 56.1 %, biologics in the form of etanercept and adalimumab by 86.4 %. IL-40 was significantly higher in patients (9.1 ± 1.3 ng/ml) than in controls (7.5 ± 2.2 ng/ml; p < 0.001). The IL-40 level was comparable between females and males and was not related to smoking, CRP, RF or anti-CCP positivity or to receiving medications. Serum IL-40 showed good validity in diagnosing RA at a cut-off value (≥8.2 ng/ml) and area under curve (AUC) (0.74), the sensitivity was 73.2 %, specificity (66.7 %), and the accuracy (70.5 %)(p < 0.001).ConclusionThe increased level of serum IL-40 and its potential diagnostic role have been revealed in RA. Further studies are needed to be implement and elucidate the complete role of IL-40 in RA.     

Interleukin-10 promoter polymorphism in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which interleukin (IL)-10 plays an important role. There are, however, controversial reports that IL-10 promoter polymorphism may be an independent marker of susceptibility and severity of RA. The aim of the present study was to examine the IL-10 promoter polymorphism in patients with RA. We examined 95 patients with rheumatoid arthritis diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction amplification was used for analysis of the promoter polymorphism of the IL-10 gene. In RA patients, the prevalence of genotypes encoding high expression of IL-10 was observed. Nevertheless, there was no association between IL-10 genotypes and age at disease diagnosis, disease activity in a physicians global assessment, and joint and extra-articular involvement. There was also no correlation between IL-10 polymorphism and disease activity parameters—erythrocyte sedimentation rate, C-reactive protein, number of swollen and tender joints, and duration of morning stiffness. We suggest that IL-10 promoter polymorphism is not a genetic risk factor for RA activity.     

High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts remission at 52 weeks in RA patients treated with adalimumab

Objective: This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA).

Methods: Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP)?Results: DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382–0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002–1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively.

Conclusion: Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.     

Serum interleukin-23 level in rheumatoid arthritis patients: Relation to disease activity and severity

Aim of the work

The aim of this study was to evaluate interleukin-23 (IL-23) level in the sera of rheumatoid arthritis (RA) patients and to determine its relation with disease activity and severity.

Inhibition of interleukin-8 synthesis by intraarticular methotrexate therapy in patientes with rheumatoid arthritis

Summary 5 Patients with definite RA and knee effusions under constant doses of DMARD therapy were treated with up to 6 intraarticular injections of 10mg methotrexate (MTX) every 3 to 7 days. A matched randomized control group who received a single i.a. injection of 40mg triamcinolone hexacetonide (TC) was monitored according to the same protocol. The intraarticular granulocyte counts and IL-8 levels decreased in all MTX treated patients on day 10–13 and stayed low in those patients who could be re-evaluated after 13 weeks. Compared to the IL-8 levels, the other tested cytokine levels showed only minor changes on day 10–13. There was no need for re-injection in the TC group during the 13 week study phase. We conclude that intraarticular MTX therapy results in a strong decrease of SF-granulocyte counts. This effect may be due to the impairment of IL-8 mediated chemotaxis by decreased IL-8 synthesis in synovial fluid mononuclear cells. Clinically, repeated intraarticular MTX therapy results in a worse 13 week outcome than i.a. steroid treatment measured in an intention-to-treat analysis. Eingegangen: 14. April 1997 Akzeptiert: 15. Januar 1998     

Predictive significance of CXCL8, CXCL10 and CXCL16 in juvenile idiopathic and rheumatoid arthritis Iraqi patients

Aim of the workTo evaluate the predicative significance of three chemokines (CXCL8, CXCL10 and CXCL16) in juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA) and to focus on their relation to some laboratory findings and clinical features.Patients and methodsSerum level of the chemokines was determined in 79 JIA and 77 RA Iraqi patients, as well as their matching controls by enzyme linked immunosorbent assay.ResultsJIA and RA patients shared significant increase of CXCL8 (24 vs. 18 and 37 vs. 15 pg/ml) and CXCL10 (38.5 vs. 17.1 and 41.5 vs. 13.2 pg/ml, respectively) compared to their controls, while no such variation observed in CXCL16 level. Regression analysis revealed that both CXCL8 and CXCL10 were significant risk factors in JIA and RA. Only rheumatoid factor-seropositive RA patients had a significantly higher CXCL10 (43 vs. 32; p = 0.014) and CXCL16 (21.2 vs. 17.7; p = 0.003) level compared seronegative patients. The CXCL10 at a cut-off value of 29.2 pg/ml in JIA showed a sensitivity of 91.1% and specificity of 91.8% and at 20.1 pg/ml in RA reached 100% and 96.2%, respectively. CXCL8 in JIA showed a sensitivity of 74.7% and specificity of 72.6% at18.6 pg/ml and in RA were 93.5% and 79.7%, respectively at 21.2 pg/ml.ConclusionsCXCL8 and CXCL10 are potential predictors of JIA and RA. CXCL10 is a more significant predictor. The CXCL16 was not found to have such impact and it might be of value in a subgroup of seropositive RA patients.     

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.     

Anti-tumor necrosis factor-alpha antibody treatment reduces serum CXCL16 levels in patients with rheumatoid arthritis

The aim of this study was to analyze the change of serum chemokins levels of CXCL16, CX3CL1/Fractalkine, and CXCL10/interferon-gamma inducible protein-10 (IP-10) with rheumatoid arthritis (RA), by infliximab treatment. The effects of infliximab treatment were studied in 23 patients with RA, over a period of 30 weeks. The serum levels of CXCL16, Fractalkine, and IP-10, were measured at the baseline, just before initial treatment, and at 14 and 30 weeks after the initial treatment, with infliximab by ELISA. The higher levels of serum CXCL16 in the RA patients before treatment with infliximab significantly decreased at 14 and 30 weeks after the initial treatment with infliximab, but the serum Fractalkine and IP-10 levels did not decrease significantly. Infliximab treatment significantly lowered the serum levels of CXCL16 in patients with RA. CXCL16 is one of the crucial chemokines regulated by infliximab treatment.     

Matrix metalloproteinase-3 as a marker of subclinical activity in rheumatoid arthritis patients: Relation to ultrasonographic activity

BackgroundRheumatoid arthritis (RA) is a chronic disease which may result in progressive joint destruction even with clinical remission. Ultrasound (US) can detect subclinical disease activity and matrix metalloproteinase 3 (MMP-3) has a role in disease activity in RA.Aim of the workTo evaluate the level of MMP-3 in RA patients and its ability to predict sonographic activity in patients with clinical remission or low disease activity (LDA).Patients and methodsThis study included 45 RA patients with a disease activity score (DAS28) <3.2 and 45 matched healthy control. US evaluation using modified German US7 score was performed and accordingly patients were classified into those with sonographic remission (grey scale 0–1) or activity. MMP-3 level was assessed by enzyme-linked immunosorbent assay. Results.The mean age of the patients was 45 ± 9.5 years and 86.7% were females. Sonographic remission was achieved in 20 (44.4 %) patients. There was a significant difference in serum MMP-3 between patients and control (17 ± 4.5 vs 6.3 ± 2.2 ng/ml; p < 0.0001). There was no difference between patients with clinical remission (n = 37) and those with LDA (n = 8). Serum MMP-3 tended to be higher in patients with sonographic activity than in those with sonographic remission (18 ± 5.3 vs 15.6 ± 2.8 ng/ml; p = 0.3). Serum MMP-3 significantly correlated with erythrocyte sedimentation rate (p = 0.002) and synovitis score (p = 0.002).ConclusionSerum MMP-3 was higher in RA patients than in control and was associated with the ultrasound synovitis score. However, serum MMP-3 was not able to differentiate patients with sonographic remission from those with subclinical activity.