Disease Activity In Early Rheumatoid Arthritis Research Articles

Association of Leptin Levels and Disease Activity in Patients with Early Rheumatoid Arthritis

Previous studies have reported a link between metabolic parameters and disease activity in rheumatoid arthritis (RA), although the evidence is limited in early RA. We aimed to investigate the relationship between disease activity and adipocytokine levels in subjects with early RA. Forty-seven patients with early RA (symptom duration ≤12 months) were enrolled. Disease activity was determined by DAS28-CRP. Patients were treated with DMARDs according to the EULAR recommendations. Subjects were tested before and five months after treatment. Early RA patients with high disease activity (DAS28-CRP > 4.9) had greater BMI (31.2 ± 6.8 kg/m2 vs. 26.7 ± 4.1 kg/m2; p = 0.006) and higher leptin levels (14.62 ± 15.60 ng/mL vs. 7.82 ± 8.00 ng/mL; p = 0.048). Levels of other adipocytokines were not significantly different. Leptin levels were similar in subjects with mild/moderate disease activity and controls. DAS28-CRP was correlated with leptin (r = 0.303, p = 0.039). Leptin levels decreased significantly after treatment (from 10.86 ± 12.34 ng/mL to 9.22 ± 9.29 ng/mL; p = 0.047) along with insulin levels (from 13.68 ± 21.90 mU/L to 7.09 ± 4.72 mU/L; p = 0.010) and HOMA-IR (from 4.39 ± 9.53 to 1.70 ± 1.38; p = 0.012). HDL cholesterol levels increased (from 41 ± 10 mg/dL48 ± 10 mg/dL; p <0.001). Leptin levels were associated with disease activity in patients with early RA and these levels decreased after treatment with DMARDs. Further research is needed to elicit leptin's role to regulate disease activity in early RA.

THU0093 EARLY REMISSION IS ASSOCIATED WITH LOWER FATIGUE LEVELS ON THE LONG TERM IN PATIENTS WITH RECENT ONSET RHEUMATOID ARTHRITIS

Background:Fatigue is mentioned as a symptom with high impact in many patients with Rheumatoid Arthritis (RA) and this symptom remains difficult to be managed by both the patient and the physician.Objectives:To investigate if rapid suppression of disease activity in early RA could impact fatigue complaints in the long run.Methods:For this study, we included patients from the 2-year pragmatic investigator-initiated Care in Early Rheumatoid Arthritis (CareRA) trial. Most patients were treated intensively, with different combinations of csDMARDs and glucocorticoid remission induction schemes, except one group without classic markers of poor prognosis that was treated with MTX weekly in monotherapy. Patients were followed up at least every 3 months, with more mandatory visits in the first 6 months of treatment. Clinical parameters including DAS28 components were registered at every visit. Fatigue was measured by the multi-dimensional fatigue inventory (MFI), a self-reported instrument consisting of 20 questions with a Likert scale from 1-5 as answer. These 20 questions can be subdivided in five subscales (0-20) of four questions (higher scores indicating higher fatigue levels): general fatigue, mental fatigue, physical fatigue, reduced activity and reduced motivation. General fatigue means the general feeling of being tired. Mental fatigue implicates concentration and memory problems. Physical fatigue implicates a lack of energy and strength. Reduced activity means that patients can do less activities for example on one day. Reduced motivation means that patients don’t want to plan or do things due to no motivation. MFI was obtained at baseline, at week 16, week 52 and week 104. Only patients with a filled-out MFI at baseline and available DAS28CRP at week 16 were included in this study.Patients were divided in 2 groups based on their response, defined as achieving or not achieving DAS28CRP remission (&lt;2.6) at week 16. These patients were classified as early responders and controls respectively. The 2 groups were compared by Mann-Whitney-U test. A generalized estimating equation (GEE) compared the 2 groups over the course of the 2-year trial per each of the 5 domains of the MFI, adjusting for baseline DAS28CRP and baseline MFI domain score.Results:Of the 379 patients recruited in the CareRA trial, 343 (90.5%) had a MFI score available at baseline and a DAS28CRP available at week 16 with 236 (68.8%) patients achieving remission, and 107 (31.2%) patients not achieving remission at week 16. After 2 years of treatment, the proportion of patients in DAS28CRP remission was still higher in the early responders versus controls (82.3% versus 63.5%, p=0.001). Every MFI domain after 2 years of treatment showed lower scores for early responders including general fatigue (p=0.017), physical fatigue (p=0.011), reduced activity (p=0.040) and mental fatigue (p=0.042) except reduced motivation (p=0.062) (see figure 1). GEE analysis demonstrated that all MFI domains differed over 2 years between patients in remission or not at week 16, including general fatigue (p&lt;0.001), physical fatigue (p&lt;0.001), reduced activity (p&lt;0.001), mental fatigue (p=0.037) and also reduced motivation (p=0.005).Figure 1.MFI domain scores at baseline and at week 104 per groupConclusion:Patients reaching remission after 16 weeks of treatment achieve lower fatigue levels over 2 years compared to patients not reaching this early remission. This study underlines the importance of early disease control. Successful early intensive treatment improves in the long run not only clinical outcomes but also an important patient preferred outcome such as fatigue.Disclosure of Interests:Diederik De Cock: None declared, Amber Nooyens: None declared, Delphine Bertrand: None declared, Veerle Stouten: None declared, Sofia Pazmino: None declared, Johan Joly: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

Ultrasonography supplements clinical exam to improve early rheumatoid arthritis disease activity monitoring in metatarsophalangeal joints.

Compared with clinical examination (CE), ultrasonography (US) provides additional and more accurate assessment of inflammation and visualization of structural damage. To better understand the effectiveness of US in metatarsophalangeal joints (MTPJs), we compared disease activity in MTPJs 2-5 assessed by CE and US, with magnetic resonance imaging (MRI) as reference standard. Treatment-naïve adult patients with early RA (ACR criteria, disease duration < 2years) were consecutively recruited. MTPJs 2-5 were assessed for swelling and tenderness, and imaged by US (Esaote MyLab70). The most symptomatic foot was imaged by peripheral MRI (1.0 Tesla). US was semiquantitatively graded for synovial thickening (ST) and power Doppler (PD) (0-3), and erosions (yes/no). MRI was semiquantitatively graded for bone marrow edema (BME), synovitis, and erosions (OMERACT). Kappa agreement, sensitivity, specificity, and predictive values were analyzed using cut-offs at ST ≥ 2, PD ≥ 1, and MRI synovitis and BME at both ≥ 1 and ≥ 2. This study included 39 patients (85% female, mean (SD) age = 51.6 (10.3)). Using MRI synovitis and BME grade ≥ 2 as the reference, PD had superior sensitivity (82%) and kappa agreement (k = 0.43) than swollen joint count (55%, k = 0.20), but similar high specificity (88%, 83%). ST and PD were often observed in clinically asymptomatic MTPJs. US detected very few MRI erosions, but several observed erosions corresponded to grade ≥ 2 MRI erosions. Clinical swelling and PD are highly specific for active inflammation in the MTPJs. US supplemented CE by allowing observation of subclinical inflammation and structural damage. Key Points • Ultrasonography detected many subclinical synovial inflammations in metatarsophalangeal joints (MTPJs), many confirmed by MRI • Ultrasonography may best be used clinically to supplement clinical examination by assessing non-swollen joints • Ultrasonography provided quick method of visualizing bone erosions that were grade ≥ 2 on MRI.

The association between anxiety and disease activity and quality of life in rheumatoid arthritis: a systematic review and meta-analysis.

In people with rheumatoid arthritis (RA), mental health problems are common, but often not recognized or treated, contributing to increased morbidity and mortality. Most studies examining the impact of mental health problems in RA have focused on depression. We aimed to determine the association between anxiety, and disease activity and quality of life (QoL) in people with RA. A systematic review and meta-analysis were performed. A protocol was registered with PROSPERO (CRD2-17062580). Databases (Web of Science, PsycINFO, CINAHL, Embase, Medline) were searched for studies examining the association between anxiety and disease activity and QoL, in adults with RA, from inception to February 2019. Primary outcome measures were DAS28 and SF-36. Eligibility screening and data extraction were completed by two reviewers. Disagreements were resolved by discussion or a third reviewer. Quality assessment was carried out using the Newcastle-Ottawa Scale. From 7712 unique citations, 60 articles were assessed for eligibility. The final review included 20 studies involving 7452 people with RA (14 cross-sectional, 6 cohort). Eleven examined disease activity, 6 reported QoL outcome measures and 3 included both. Anxiety was associated with increased disease activity and worse QoL. Meta-analysis showed anxiety to be correlated with increased DAS28 scores (r = 0.23, CI 0.14, 0.31) and reduced physical (r = - 0.39, CI - 0.57, - 0.20) and mental QoL (- 0.50, CI - 0.57, - 0.43). Anxiety in people with RA is associated with increased disease activity and worse QoL. Improved recognition and management of comorbid anxiety may help to improve outcomes for people with RA.Key Points• This is the first systematic review and meta-analysis to examine the relationship between anxiety and disease activity and QoL in people with RA.• Anxiety was associated with higher disease activity both cross-sectionally and at up to 12-month follow-up.• Anxiety may have a more significant impact on disease activity in early RA, highlighting the importance of early recognition and management of comorbid anxiety.• People with anxiety had poorer self-reported physical and mental QoL, although there was some heterogeneity in study findings, particularly for physical QoL (I2= 78.5%).

Biologics: A tectonic shift in the management of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints which if ongoing, has a significant bearing in the quality of life and has a variety of systemic manifestation which reduces the overall life span due to an ongoing inflammatory process. There has been a shift in the management of RA right from the early identification of the disease to targeting the pathogenic mechanisms. The changing modalities with emphasis on remission and low disease activity in early RA should be the primary goal. Disease control of RA with the use of combination synthetic disease modifying anti-rheumatic drugs or in combination with biological agents have improved disease-related outcomes. This prevents the progression of disease, morbidity, and has a significant bearing on the overall economic productivity of the patient and the society. Costs of the biological drugs is a major hurdle in their usage. Introduction of biosimilars have lead to a decrease in the cost of the biological molecules and hence their use becoming more widespread. The purpose of this review is to highlight the changing treatment modalities with the advent of biological disease modifiers in RA and a rationale for their use. The strategy in the treatment of RA should be goal directed rather than just relief of symptoms.

Determinants of Perceived Health Nonimprovement in Early Rheumatoid Arthritis Patients With Favorable Treatment Outcomes.

To explore the association between achieving favorable clinical outcomes and patients' perceived change in overall health status after 12 months of treat-to-target in patients with early rheumatoid arthritis (RA) and to identify determinants of subjective nonimprovement. Baseline and 12-month data of patients included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study with at least a moderate response (by European League Against Rheumatism criteria) after 1 year were selected for analysis. Logistic regression analysis was used to identify factors associated with nonimproved perceived overall health status at 12 months. At 12 months, 75 of 210 patients (35%) did not consider their health to have improved despite having achieved favorable clinical outcomes. Relative change from baseline in pain (Wald = 20.20; P < 0.01) and fatigue (Wald = 5.58; P = 0.02) was independently associated with nonimproved perceived overall health status. The results were similar when only patients with ≤1 swollen joint were analyzed. An improvement of 55% in pain measured on a visual analog scale was found to discriminate reasonably well between patients who considered their health to have improved versus patients who did not, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval 0.61-0.78). These results demonstrate that clinical improvements do not equate with improved subjective health for all patients. The association of nonimprovement with changes in pain and fatigue suggest that it might be worthwhile to monitor and address pain and fatigue in addition to and independently of disease activity in early RA.

Role of cartilage oligomeric matrix protein (COMP) as a prognostic biomarker in follow-up of early rheumatoid arthritis patients: Correlation to musculoskeletal ultrasonographic findings

Aim of the workTo assess the level of serum cartilage oligomeric matrix protein (COMP) in early rheumatoid arthritis (RA) patients and study its relation to disease activity and musculoskeletal ultrasound (MSUS) findings. Patients and methodsThe study included 40 early RA patients. Disease activity score (DAS28) was assessed. Serum COMP level was measured and MSUS findings of the small joints of hands done at base line and after 6 months of follow up.20 age and sex matched control were included. ResultsPatients age was 38.8 ± 9.3 years; 36 females and 4 males and disease duration 6.7 ± 3.5 years. Serum COMP was significantly higher in patients (median 190 U/L; 90–750 U/L) compared to control (90 U/L; 80–130 U/L)(p < .001) being higher in more active (250 U/L) (p = .001) and significantly correlated with baseline synovial inflammation (p = .009). COMP levels were lowered after 6 months of receiving treatment (110 U/L; 30–180 U/L) (p < .001). The presence of bony erosions increased with more active disease (p = .003). There was a significant reduction in the erythrocyte sedimentation rate and COMP at follow up (p < .0001 and p = .001 respectively). No correlation was found between the COMP level with C-reactive protein, ESR, MSUS score or bony erosions at follow up. ConclusionsCOMP significantly correlated with disease activity in early RA and could be used as a marker of activity. It correlates significantly with synovial inflammation detected by power Doppler. COMP may reflect the outcome and could be used as a prognostic marker in RA patients. COMP did not significantly correlate with bone erosions.

Serum and synovial matrix metalloproteinase-3 as markers of disease activity in early rheumatoid arthritis

Matrix metalloprotein ase-3 (MMP-3) is one of the MMPs produced in rheumatoid arthritis (RA) joints. The aim of this study was to evaluate serum and synovial fluid (SF) MMP-3 as markers of disease activity in early RA. Thirty early RA patients together with age-matched and sex-matched 12 primary knee osteoarthritis patients and 12 apparently healthy individuals as control groups were enrolled in this study. MMP-3 was measured in serum and SF samples using enzyme-linked immunosorbent assay. Assessment of disease activity in RA patients was carried out using disease activity score-28 (DAS-28), and radiographs of the hands, wrists, and forefeet were obtained and evaluated according to Larsen score. As regards mean serum levels of MMP-3, there was a statistically significant elevation in RA patients compared with the control groups (P<0.001). Moreover, the mean SF levels of MMP-3 in RA patients were statistically significantly higher than that in osteoarthritis patients (P<0.001). In RA patients, there was a statistically significant difference (P<0.001) between mean serum and SF levels, being higher in the SF. There was a statistically significant positive correlation (P<0.05) between serum MMP-3 with disease duration, DAS-28, and Larsen score. As regards mean SF MMP-3 levels, there was a high statistically significant positive correlation (P<0.001) with DAS-28 and a statistically significant positive correlation (P<0.05) with Larsen score. Elevated serum and synovial MMP-3 levels reflect disease activity in RA patients; thus, it could be used as a useful marker for disease activity. The cross-sectional design of our study did not allow us to produce conclusions with respect to disease course and prognosis. Thus, we recommend further studies on large numbers of patients and serial measurements of MMP-3 to determine the rate of disease progression.

A population model of early rheumatoid arthritis disease activity during treatment with methotrexate, sulfasalazine and hydroxychloroquine.

To develop a population model describing the disease activity (DAS28) time course in patients with early rheumatoid arthritis (RA) treated with triple disease-modifying anti-rheumatic drug (DMARD) therapy (methotrexate, sulfasalazine and hydroxychloroquine). DAS28 was obtained in 263 patients with early RA from initiation of therapy until 60 weeks. Using NONMEM(®), base models (DAS28 vs. time) and covariate influences were investigated for the population. The best model was an exponential model of DAS28 vs. time that was additive to baseline DAS28, with covariance between parameters, and a combined residual error model. Age and patient smoking history were covariates significantly affecting response to therapy. Population estimates were baseline DAS28 (5.7), extent of change in DAS28 (-2.8) and the half-life of disease activity (6.2 weeks; time to steady disease state achieved within approximately 30 weeks). Older individuals exhibited more severe baseline DAS28, described by a power function centred around 57 years (baseline DAS28 for 40- and 70-year-old patients were 5.4 vs. 5.8, respectively) and current smokers took longer to achieve a steady disease state (approximately 50 weeks). There was considerable within-patient random variability in DAS28 over time (empirical 90% CI for DAS28 in a population typical patient at 60 weeks: 1.8, 4.2 with median value of 2.8). This is the first report of a disease activity model for early RA treated with triple DMARD therapy. Smoking and age were identified as covariates.

Further optimization of the reliability of the 28-joint disease activity score in patients with early rheumatoid arthritis.

BackgroundThe 28-joint Disease Activity Score (DAS28) combines scores on a 28-tender and swollen joint count (TJC28 and SJC28), a patient-reported measure for general health (GH), and an inflammatory marker (either the erythrocyte sedimentation rate [ESR] or the C-reactive protein [CRP]) into a composite measure of disease activity in rheumatoid arthritis (RA). This study examined the reliability of the DAS28 in patients with early RA using principles from generalizability theory and evaluated whether it could be increased by adjusting individual DAS28 component weights.MethodsPatients were drawn from the DREAM registry and classified into a “fast response” group (N = 466) and “slow response” group (N = 80), depending on their pace of reaching remission. Composite reliabilities of the DAS28-ESR and DAS28-CRP were determined with the individual components' reliability, weights, variances, error variances, correlations and covariances. Weight optimization was performed by minimizing the error variance of the index.ResultsComposite reliabilities of 0.85 and 0.86 were found for the DAS28-ESR and DAS28-CRP, respectively, and were approximately equal across patients groups. Component reliabilities, however, varied widely both within and between sub-groups, ranging from 0.614 for GH (“slow response” group) to 0.912 for ESR (“fast response” group). Weight optimization increased composite reliability even further. In the total and “fast response” groups, this was achieved mostly by decreasing the weight of the TJC28 and GH. In the “slow response” group, though, the weights of the TJC28 and SJC28 were increased, while those of the inflammatory markers and GH were substantially decreased.ConclusionsThe DAS28-ESR and the DAS28-CRP are reliable instruments for assessing disease activity in early RA and reliability can be increased even further by adjusting component weights. Given the low reliability and weightings of the general health component across subgroups it is recommended to explore alternative patient-reported outcome measures for inclusion in the DAS28.

THU0273 Changes in Patient-Reported Joint Counts and Composite Indices Can Identify Flare of Disease Activity in Recent Onset

BackgroundTender & swollen joint counts (JCs) have been identified as core domains for assessment of flare in rheumatoid arthritis (RA)1,2.ObjectivesTo assess the responsiveness and discriminative validity of patient-reported JCs, separately...

Metabolic syndrome in rheumatoid arthritis: role of adiponectin (preliminary results)

The clinical value of the disorders and diseases integrated within the metabolic syndrome (MS) is in the combination of traditional risk factors for cardiovascular diseases (CVD), which significantly accelerates the development of cardiovascular events (CVEs). The detection rate for MS in patients with rheumatoid arthritis (RA) is shown to be higher than in the controls regardless of the diagnostic criteria for MS. At present, there are confusing data on the role of adipokins in RA. Objective: to determine the rate of MS and its components in RA patients and the association of the level of adipokin (adiponectin) with the components of MS in relation to the duration of RA. Subjects and methods: The investigation enrolled 69 RA patients divided into two groups: 1) 34 patients with early-stage ( 2-year) RA. Results. MS occurred in 12 (17.4%) of the 69 patients with RA. There was central (abdominal) obesity in 37 (53.6%) patients with RA, hypertension in 29 (42%), low high-density cholesterol levels in 20 (29%), hyperglycemia in 11 (15.9%), and hypertriglyceridemia in 10 (14.5%). According to the presence or absence of MS, the patients were divided into 2 groups: 1) 12 patients with MS; 2) 57 without MS. In the patients with RA and MS, the duration of the disease was shorter; DAS28 and CDAI were higher than in those without MS: 15.4 [7; 24] months versus 51.8 [6; 72] months; DAS28 was 5.8 [4.9; 6.7] scores versus 5.1 [4.5; 5.8] scores; CDAI: 34.8 [21.8; 41.4] scores versus 24.2 [18; 31] scores, respectively (p 2-year RA group displayed no relationship between adipokins, activity markers, and metabolic disturbances. Conclusion. The preliminary results suggest the high rate of MS in patients with a high level of early RA disease activity untreated with disease-modifying antirheumatic drugs, thus determining the high risk of CVEs just at disease onset. The role of adiponectin in the development of MS, CVEs in rheumatic diseases remains to be solved, which is the subject of further investigations. It is possible that normalization of adiponectin concentrations may promote reductions in the incidence of CVD, mortality rates due to atherosclerosis-induced CVEs, and the prevalence of MS and insulin resistance.

Investigation of tear osmolarity in early rheumatoid arthritis: relation to disease activity

ObjectiveTo investigate the frequency of dry eye (DE) by measuring tear osmolarity (TO) with the recently introduced TearLab system (TearLab Corp, San Diego, Calif.) in patients with early rheumatoid arthritis (ERA) and the relationship between the severity of DE and ERA disease activity. DesignProspective study ParticipantsSixty-four eyes of 64 newly diagnosed and untreated patients with ERA were enrolled in this study. MethodsTO measurements, tear break-up time (TBUT), and Schirmer tests were performed. ERA disease activity was evaluated according to the disease activity score 28 (DAS28). The patients were divided into 3 groups according to DAS28 scores as follows: mild (DAS28 ≤ 3.2), moderate (3.2 < DAS28 ≤ 5.1), and severe (DAS28 > 5.1). ResultsDE was identified in 46 (71.8%) patients with ERA according to the TO values. There were significant differences among these groups concerning TO (p = 0.001) and TBUT (p = 0.005) scores, whereas there was no significant difference between these groups regarding Schirmer scores (p = 0.200). In addition, DAS28 values were positively correlated with TO values (r = 0.710, p < 0.001), negatively correlated with Schirmer scores, (r = –0.251, p = 0.045), and negatively correlated with TBUT scores (r = –0.335, p = 0.007) among all patients. ConclusionsOur study demonstrated a relationship between the ERA disease activity and severity of DE by using TO measurements with the TearLab system. Therefore, TO measurement could be added to other classical DE tests for diagnosing DE and for assessing the degree of disease activity of ERA.

FRI0062 Evaluation of a multi-biomarker disease activity (vectra ™ da algorithm) in early rheumatoid arthritis and unclassified arthritis patients

BackgroundAccurate and frequent assessment of rheumatoid arthritis (RA) is critical for optimal treatment planning and would benefit from the availability of an objective, sensitive and robust way to measure disease...

AB0362 Tight control of disease activity by conventional DMARDs could minimize the use of biological therapies in patients with early rheumatoid arthritis: Data from an early arthritis clinic in hong kong

ObjectivesTo examine the treatment outcome at 1 year of patients treated with tight control of the disease in a prospective cohort of patients with newly diagnosed rheumatoid arthritis (RA).MethodsAll patients...

SAT0041 Metabolic Syndrome in Early and Established Rheumatoid Arthritis: Role of Adipokines

BackgroundMetabolic syndrome (MeS) is associated with an increased, independent risk for cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Adipose tissue is active endocrine organ that produces hormone-like substances...

Standardized grip strength as an outcome measure in early rheumatoid arthritis

Objectives: Patients with rheumatoid arthritis (RA) suffer progressive loss of hand function and have weaker hand grip than the healthy population. In this study we aimed to validate hand grip strength standardized by age and gender (z score) against currently accepted clinical measures of disease activity.Method: Electronic records of patients with a diagnosis of RA seen between April 2007 and December 2011 were screened for the documentation of tender and swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), along with patient global activity score and grip strength. Bilateral grip strengths were converted to z scores on the basis of previously published age- and gender-corrected normative data for grip strength. The z scores were then correlated against components of disease activity scores.Results: Ninety patients diagnosed with RA had been seen 602 times within 2 years of diagnosis. Hand grip data were available for 204 visits. There was a statistically significant inverse correlation between grip strength z scores and the tested variables. The sensitivity and specificity of a hand grip z score of −1.5 for predicting remission were, respectively, 70% and 76% for the right hand and 82% and 69% for the left hand.Conclusions: Hand grip testing and subsequent conversion to z scores corrected for age and gender correlate with disease activity in early RA. We have shown that the grip strength z scores can discriminate between various disease states, and the strength seems to return to near normative data when the disease is in remission.

The Role of IL-17, Metaphase Reactants on Patients with Early Rheumatoid Arthritis disease Activity and Trace Elements

Rheumatoid arthritis (RA) represents the most common form of chronic inflammatory joint disease leading to cartilage and bone destruction, It affects approximately 1-2 % of world's population. The inflammatory process causes diffuse thickening and hyperplasia of the joint Interleukin (IL)-17 is a pleiotropic pro-inflammatory cytokine produced from Th17 cells. IL-17A is the prototypic member belonging to a family of 6 ranging from IL-17A to IL-17F. IL-17A mediates its biological effects through binding to a receptor complex consisting of IL-17RCA and IL-17RCC subunits. Objective. To assess the role of IL-17 on the disease process of Rheumatoid arthritis and the effects on the trace elements such as Zinc, copper , Magnesium. Subjects and method: A total of 60 patients with early Rheumatoid Arthritis were studied. Their ages ranged from 20-52 years with a mean age of ( 39.3 ± 9.01)years. , while the range was between (20-51) years and the mean was (37.5 ± 8.6) years for healthy control non significant difference P > 0.4 with no complaint of other chronic or systemic diseases were considered as control. the samples were collected during period from ( December 2012 - july 2013 ). the mean disease duration of RA was (3.27±1.2) month. Blood samples were collected from patients and controls to assess Erythrocyte Sedimentation Rate (ESR) and serum levels of White blood cells ( WBC), Hemoglobin (Hb), Interleukin-17A and were estimated by agglutination test, and IL-17A was estimated by (ELIZA).

Serum Matrix Metalloproteinase-3 in Comparison with Acute Phase Proteins as a Marker of Disease Activity and Radiographic Damage in Early Rheumatoid Arthritis

Matrix metalloproteinase-3 (MMP-3) is involved in the immunopathogenesis of rheumatoid arthritis (RA), but little is known about its relationship to genetic susceptibility and biomarkers of disease activity, especially acute phase reactants in early RA. MMP-3 was measured by ELISA in serum samples of 128 disease-modifying, drug-naïve patients and analysed in relation to shared epitope genotype, a range of circulating chemokines/cytokines, acute phase reactants, autoantibodies, cartilage oligomeric protein (COMP), and the simplified disease activity index (SDAI). MMP-3 was elevated >1.86 ng/ml in 56.25% of patients (P < 0.0001), correlated with several biomarkers, notably IL-8, IL-6, IFN γ, VEGF and COMP (r values = 0.22–0.33, P < 0.014–0.0001) and with CRP and SAA levels (r = 0.40 and 0.41, resp., P < 0.0000) and SDAI (r = 0.29, P < 0.0001), but not with erosions or nodulosis. However, the correlations of CRP and SAA with SDAI were stronger (respective values of 0.63 and 0.54, P < 0.001 for both). COMP correlated with smoking, RF, and MMP-3. MMP-3 is significantly associated with disease activity, inflammatory mediators and cartilage breakdown, making it a potential biomarker of disease severity, but seemingly less useful than CRP and SAA as a biomarker of disease activity in early RA.

Correlation between DAS-28 and neopterin as a biochemical marker of immune system activation in early rheumatoid arthritis

Objective: The objective of this study was to evaluate neopterin plasma concentrations in patients with early Rheumatoid Arthritis (RA) and correlate them with disease activity. Methods: This is a 28-month prospective study carried out on 65 individuals. There were 27 patients with early RA and 38 healthy volunteers as control group. Enzyme immunoassay was used to measure concentrations of neopterin and anti-cyclic citrullinated peptide (CCP) antibodies. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured turbidimetrically, and antinuclear antibodies (ANA) were detected by immunofluorescence. Patients with early RA disease activity were divided into 4 groups according to DAS-28 criteria. Neopterin concentrations in RA patients were compared to conventional RA diagnostic serological markers. Results: Healthy volunteers had a mean neopterin concentration of 5.63 ± 0.38 [1.36–9.93] nmol. L− 1. A statistically significant elevation of neopterin mean concentration was found on early RA patients: mean value of 8.92 ± 0.93 [3.94–28.3] nmol. L− 1 (p < 0.001). Pearson product moment correlation suggests a correlation between neopterin concentrations and DAS-28 (r = 0.208, p = 0.065). The analysis of the mean values grouped according with the DAS-28 criteria showed a correspondence between these means, with a Pearson correlation coefficient r = 0.979, p = 0.021. CRP concentrations also showed a similar trend. Anti-CCP antibodies and RF revealed a positive relationship with RA activity. Such a correlation was not found with ANA results. Conclusions: The elevation of plasma neopterin concentrations in early RA patients may indicate stimulation of immune response. Good correlation between neopterin concentrations and DAS-28 may facilitate assessing disease activity.