Rheumatoid Arthritis Articular Damage Score Research Articles

IKKε aggravates inflammatory response via activation of NF-κB in rheumatoid arthritis.

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease, whereas its cause still remains elusive. Typical pathological manifestations of RA include persistent synovitis and bone degeneration in the surrounding joints. Although the incidence of RA is high in population, currently there have been no effective cures for it. The purpose of this study is to investigate the therapeutic effects and main mechanism of IKKε (inhibitor of nuclear factor kappa-B kinase ε) in collagen II induced- Rheumatoid Arthritis (CIA) mice model. IKKε-/- and wild-type (WT) littermate control mice were intraperitoneally injected with 5 mg/kg collagen II monoclonal antibody cocktail (Cab) for 5 days. After that, the nociception threshold and clinical rheumatoid arthritis articular damage score of mice were evaluated. After 5 days-CAb treatment, serum levels of a series of inflammatory cytokines including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and interferon (IFN) were detected with enzyme-linked immunosorbent assay (ELISA) in both groups. Besides, Real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) was used to evaluate the expression of these inflammatory cytokines in plantar tissues. In addition, Western blot was performed to investigate the protein levels of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B) signaling pathway. Moreover, WT mice receiving CAb were further applied with or without IKK inhibitor amlexanox (25 mg/kg) to investigate the expression of the above-mentioned inflammatory cytokines. Our work showed that IKKε-/- mice with CIA displayed less nociception and suppressed inflammatory response than WT mice. Meanwhile, the clinical rheumatoid arthritis articular damage scores were significantly decreased in IKKε-/- mice. The levels of TNF-α, IL-1β, IL-6 in serum and plantar tissues in IKKε-/- mice were significantly lower than those in WT mice. Besides, NF-κB expression in IKKε-/- mice was significantly decreased. Similarly, the same phenotype was observed in WT mice administrated with IKKε inhibitor amlexanox as that of IKKε-/- mice, indicating that inflammatory and nociception responses were remarkably decreased than those of the negative controls. IKKε plays an important role in promoting nociception and inflammatory response in CIA. Our research demonstrated that knockout of IKKε may serve as a new direction for clinical prevention and treatment of rheumatoid arthritis. IKKε inhibitor amlexanox may become a new drug for the treatment of rheumatoid arthritis.

Assessment of long-term articular damage and function in rheumatoid arthritis patients

Aim of the workThis study aimed to assess long-term articular damage and function in rheumatoid arthritis (RA) patients in relation to the type of treatment. Early disease modifying anti-rheumatic drug (DMARD) therapy has not been evaluated in this study. Patients and methodsOne hundred and fifty RA patients (141 females and 9 males) with disease duration more than five years and disease activity score-28 (DAS-28) <3.2 were included in this study. Sixty patients received disease modifying anti-rheumatic drugs (DMARDs) (group A), 60 received DMARDs and corticosteroids (CS) (group B), and 30 patients received CS only (group C). The functional outcome was assessed using the Modified Health Assessment Questionnaire (MHAQ). The articular damage was measured by using Rheumatoid Arthritis Articular Damage (RAAD) Score. The van der Heijde modification of the Sharp erosion score was used to define the plain X-ray of both hands and feet. ResultsThe mean age of the patients was 49.3 ± 11.5 years, and disease duration was 12 ± 7.9 years. There was a significant difference between the RAAD, visual analogue scale and MHAQ scores among the three groups (p = 0.001), with higher score in group C followed by B. By using Multiple regression analysis to examine the relationship between RAAD score and other independent variables there was a significant association of the RAAD score with higher X-ray score (p < 0.001) and with patients taking steroids only (p = 0.001). ConclusionAlthough, use of corticosteroids may help to control the disease activity, but it increases the risk of overall joint damage.

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

ObjectiveEpigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients.MethodsPeripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti‐cyclic citrullinated protein). Fluorescence‐activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome‐wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators.ResultsDifferential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type–specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified.ConclusionMethylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity.

Serum serotonin in rheumatoid arthritis patients: Relation to rheumatoid factor positivity, clinical manifestations and fibromyalgia

Aim of the workTo estimate serum level of serotonin in rheumatoid arthritis (RA) patients and study its relation with various clinical data, radiographic scores and fibromyalgia. Patients and methodsThis study involved eighty RA patients divided equally according to rheumatoid factor (RF) positivity. Modified Health Assessment Questionnaire, disease activity score in 28-joints (DAS 28), visual analogue scale of pain, Short Form Health Survey for mental and physical health, fibromyalgia questionnaire, RA Articular Damage score and radiological joint damage by van der Heijde modification were assessed. Serum level for serotonin was measured for all patients. ResultsThe mean age of seronegative patients was 41.7±10.7years; 36 females and 4 males and of seropositive (44.9±12.9years and were 34 females and 6 males). Serum serotonin level was high in RA patients compared to control (129.8±99.1ng/ml vs 79.6±54.5ng/ml respectively, p=0.001). Serum serotonin was higher in seropositive than seronegative (155.9±93.2 vs 101.5±99.4ng/ml respectively, p=0.007). Fibromyalgia syndrome (FMS) was associated with a significant lower serotonin level in both groups (p<0.005). High serotonin level was associated with combined disease modifying antirheumatic drugs (p=0.04) in seronegative patients. A lower serotonin level was associated with corticosteroids administration and dry eye (p=0.03, p=0.004 respectively) in seropositive cases. A significant correlation was present between serotonin level with erythrocyte sedimentation rate, vitality energy and mental health (r=0.4, p<0.05) in seropositive patients. ConclusionSerum serotonin level was high in RA, especially in seropositive patients. It demonstrated central antidepressant and peripheral pro-inflammatory role. The SSRI could be of benefit only in RA with FMS.

S100A8/A9 as a biomarker for synovial inflammation and joint damage in patients with rheumatoid arthritis

S100A8 and S100A9 are major leukocyte proteins, known as damage-associated molecular patterns, found at high concentrations in the synovial fluid of patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is secreted by activated leukocytes and binds to Toll-like receptor 4, which mediates downstream signaling and promotes inflammation and autoimmunity. Serum and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA than in patients with osteoarthritis or miscellaneous inflammatory arthritis. Serum levels of S100A8/A9 are significantly correlated with clinical and laboratory markers of inflammation, such as C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28 joints. Significant correlations have also been found between S100A8/A9 and radiographic and clinical assessments of joint damage, such as hand radiographs and the Rheumatoid Arthritis Articular Damage score. In addition, among known inflammatory markers, S100A8/A9 has the strongest correlation with total sum scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9 are independently associated with progression of joint destruction in longitudinal studies and are responsive to change during conventional and biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic and prognostic biomarker for RA.

Patterns and predictors of joint damage as assessed by the rheumatoid arthritis articular damage (RAAD) score in South Africans with established rheumatoid arthritis

This study aimed to determine the pattern and predictors of joint damage measured by the rheumatoid arthritis articular damage (RAAD) score and to describe its relationship to functional disability in patients with established rheumatoid arthritis (RA). One hundred Black patients with RA of disease duration ≥5 years were studied cross-sectionally. Data collected included socio-demographics, disease duration, smoking, body mass index (BMI), extraarticular features, rheumatoid factor (RF), haemoglobin (Hb), disease activity (DAS28), delay in disease-modifying antirheumatic drug initiation (DMARD lag) and treatment history. As outcome measures, the RAAD score and modified Health Assessment Questionnaire (mHAQ-DI) were used to assess joint damage and disability, respectively. Data were analysed by univariate and multivariate analyses. The mean RAAD score was 28.2 ± 12.8 for a mean disease duration of 17.5 ± 8.5 years. The majority of patients still had active disease (mean DAS28 4.4) and severe disability (mean mHAQ-DI 1.9), reflected in part by a long mean DMARD lag (9 years). Wrist and ankle joints were commonly involved. Multivariate analysis revealed that longer disease duration, higher RF titres and lower BMI were significant independent predictors of a higher RAAD score. The mHAQ-DI was significantly associated with DAS28, RAAD, education and Hb. Our results provide support for aspects of validity of the RAAD score and for its use in under-resourced settings. Further longitudinal studies are needed to evaluate its sensitivity to change in monitoring joint damage. Patterns of joint involvement and the inverse relationship between BMI and joint damage also merit further investigation in Black RA patients.

Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant. Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049). Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role. Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interest

Calprotectin (a major S100 leucocyte protein) predicts 10-year radiographic progression in patients with rheumatoid arthritis

Background:Plasma levels of calprotectin, a major S100 leucocyte protein, are cross-sectionally associated with clinical and laboratory markers of inflammation and with radiographic damage in rheumatoid arthritis (RA). High amounts of...

Articular damage in adults with juvenile idiopathic arthritis

The goal of this study was to assess the long-term articular damage in adults with juvenile idiopathic arthritis (JIA) using the Rheumatoid Arthritis Articular Damage (RAAD) score and to determine any associations between the disease-related parameters and RAAD score. Thirty-eight adults identified with JIA at 18 years of age or older with disease duration of at least 5 years were assessed by means of the RAAD score. Patients were divided into three groups according to disease duration as 5-10 years (group 1), 11-15 years (group 2) and more than 16 years (group 3), and into three groups according to JIA subtypes as seropositive polyarticular (group A), seronegative polyarticular (group B), and oligoarticular (group C). Functional disability, functional status, disease activity and depression were measured by Health Assessment Questionnaire (HAQ), Steinbrocker classification, Disease Activity Score 28 (DAS 28), and Beck Depression Inventory, respectively. We investigated any possible associations between the RAAD score and groups, sex, age at onset of the disease, HAQ, Steinbrocker classification, DAS 28, and Beck Depression Inventory. We observed significant differences in RAAD scores according to groups A, B, C (p < 0.01), but not according to groups 1, 2, 3 or sex (p > 0.05). While the RAAD score correlated well with HAQ (p < 0.001), Steinbrocker classification (p < 0.001) and DAS 28 (p < 0.01), it did not correlate with age at onset of the disease (p > 0.05) or Beck Depression Inventory (p > 0.05). Seropositive polyarticular patients demonstrate the worst articular damage scores. Even though articular damage does not progress over time and JIA frequently has a benign course, care should be given to establishing regular follow-up periods and well-arranged treatments, especially for seropositive polyarticular groups, to maintain satisfactory long-term disease outcome throughout the lives of JIA patients.

Articular damage in late rheumatoid arthritis

This study aims to examine the long-term articular damage in rheumatoid arthritis (RA) patients according to rheumatoid arthritis articular damage (RAAD) score and to evaluate the parameters correlated with this score. The RAAD score was assessed in 85 RA patients who had the disease for more than 10 years. Patients were divided into three groups according to duration of the disease: group 1, 10-14 years; group 2, 15-19 years; and group 3, more than 20 years. Patients were also divided into three groups according to the time of initiation of treatment with disease-modifying antirheumatic drugs: group A, within the first 2 years, group B, between 2 and 5 years; and group C, after 5 years. We investigated the RAAD score relationship between groups 1, 2, 3; groups A, B, C; sex; drug compliance; age of onset of the disease; and Health Assessment Questionnaire (HAQ). We observed significant differences in RAAD scores according to groups 1, 2, 3 (p<0.01), but not to groups A, B, C; sex; or drug compliance (p>0.05). While the RAAD score correlated well with the HAQ (r=0.560, p<0.001), it did not correlate with the age at onset of the disease (p>0.05). As RA is not a benign disease and articular damage progresses over time, the goal of RA therapy must be to maintain a response before the onset of irreversible damage and loss of function.

Hand disability and related variables in patients with rheumatoid arthritis

To carry out a cross-sectional study of patients with rheumatoid arthritis (RA) for hand disability, articular damage and to define their relation with demographic, laboratory and clinical parameters. The study included 105 RA patients with a mean age of 49.4 years. Demographic parameters of the patients were recorded. Clinical parameters including disease duration, duration of morning stiffness, pain assessed by visual analog scale, Ritchie Articular Index, grip strength, lateral, tip and three-fingered pinch, and laboratory parameters comprising C-reactive protein, erythrocyte sedimentation rate and rheumatoid factor were evaluated in all patients. The Rheumatoid Arthritis Articular Damage (RAAD) score was used to assess the irreversible articular damage and deformities of the hand. Hand disability was assessed by the special hand disability index of Standford Health Assessment Questionnaire (HAQ). Hand disabilities of various levels were detected in 81% of the patients. Disease duration, grip strength, pinch measurements, clinical and laboratory activity parameters were strongly correlated with hand disability (p<0.01). Hand disability was more related to disease activity parameters than articular damage (p<0.01 and p<0.05, respectively). Grip strength and pinch measurements were the most related parameters with hand disability. The disability scores were significantly higher in female patients (p<0.01). The RAAD score was correlated with disease duration and grip strength (p<0.01). The clinical and laboratory parameters and seropositivity were not correlated with articular damage assessed by RAAD score (p>0.05). Our data suggest that grip strength and pinch measurements seem to be the most related variables with hand disability and articular damage. Therefore, grip strength and pinch measurement should be included in the evaluation and follow-up of the patients with RA in hand rehabilitation units.

Reliability of the rheumatoid arthritis articular damage score in Tunisian patients

The clinical rheumatoid arthritis articular damage (RAAD) score is easy to perform and showed good intraobserver reliability. It correlates well with the Larsen score and disease duration and can be recommended for rheumatoid arthritis patients' follow-up in developing countries.