Rheumatoid Arthritis Disease Activity Parameters Research Articles

Association of CD90 Expression by CD14+ Dendritic-Shaped Cells in Rheumatoid Arthritis Synovial Tissue With Chronic Inflammation.

ObjectiveCD14+ dendritic‐shaped cells show a dendritic morphology under the electron microscopy and engage in a pseudoemperipolesis phenomenon with lymphocytes. CD90 has been used as a marker of a major subset of fibroblast‐like synoviocytes in rheumatoid arthritis (RA). In this study, we investigated the significance of CD90 expression in CD14+ dendritic‐shaped cells and its correlation with RA chronic inflammation.MethodsDouble immunofluorescence staining for CD14 and CD90 was performed in the collected tissues, including 12 active RA synovial tissues. The localization of CD14+CD90+ cells, the percentages of CD14+CD90+ cells and vascular areas, the degree of synovitis, and clinical data were investigated. Furthermore, CD14+CD90+ cells analyzed by flow cytometry (CD14highCD90intermediate (int) cells) were sorted from RA synovial cells, and we examined their potential to differentiate into dendritic cells.ResultsDouble immunofluorescence staining showed that CD14+CD90+ cells were abundant in RA synovial tissues. The percentages of CD14+CD90+ cells and vascular areas correlated with some of the Krenn synovitis scores, but neither showed a strong correlation with RA disease activity parameters. Flow cytometry analysis indicated that CD14highCD90int cells were more abundant in both peripheral blood samples and synovial tissues in patients with active RA. CD14highCD90int cells were more likely to differentiate into dendritic cells in vitro.ConclusionCD14+ dendritic‐shaped cells expressed CD90 in the perivascular areas of RA synovial tissues. These findings suggest that CD14+CD90+ dendritic‐shaped cells migrate from the peripheral blood to the synovial tissue, the site of inflammation, and may contribute to the chronic inflammation of RA as dendritic progenitor cells.

The impact of tocilizumab on anxiety and depression in patients with rheumatoid arthritis.

Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4weeks and study completion. Ultimately, 91 patients were included in the study. The mean age was 54years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ-DI (r=.4, .42), DAS28 (r=.29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P<.01). This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.

Efficacy of a mouthwash containing essential oils and curcumin as an adjunct to nonsurgical periodontal therapy among rheumatoid arthritis patients with chronic periodontitis: A randomized controlled trial

The purpose of this study was to assess the efficacy of mouthwash containing essential oils and curcumin (MEC) as an adjunct to nonsurgical periodontal therapy on the disease activity of rheumatoid arthritis (RA) among RA patients with chronic periodontitis (CP). A triple-blinded controlled trial was conducted among 45 female RA patients with CP randomized into three treatment groups as follows: Group A: scaling and root planing (SRP) with 0.2% chlorhexidine mouthwash as an adjunct (n = 15), Group B: SRP with MEC as an adjunct (n = 15), and Group C: SRP alone (n = 15). RA disease activity was assessed using erythrocyte sedimentation rate, serum C-reactive protein, serum anti-citrullinated protein antibody, and serum rheumatoid factor. Periodontal disease activity was assessed using plaque index, clinical attachment level (CAL), and pocket depth (PD). All parameters were recorded at baseline and 6 weeks thereafter. Data were assessed using one-way ANOVA and paired t-test. A significant reduction in periodontal and RA disease activity parameters was observed from baseline to 6 weeks following intervention (P < 0.05). The highest percentage of mean reduction in plaque index and RA parameters from baseline to 6 weeks was observed in Group B followed by Groups A and C. The highest percentage of mean reduction in PD and CAL was observed in Group A followed by Groups B and C (P < 0.001). This study reveals that MEC as an adjunct to SRP is effective in reducing the disease activity of RA and CP, thereby warranting the use of the same.

Hypothyroidism in patients with rheumatoid arthritis and its relation to disease activity

The relationship between thyroid disease and rheumatic disorders has been the subject of considerable debate. Thyroid abnormal function and/or autoimmune thyroid disease were observed in patients with rheumatoid arthritis (RA), which could be attributed to the natural feature of autoimmune diseases and their tendency to overlap. Consideration of the fact that autoimmunity plays a role in the pathogenesis of both RA and hypothyroidism has raised the need to study the frequency of hypothyroidism and thyroid antibodies in RA patients and their relation to disease activity. One hundred and fifty RA patients and 50 control participants were included in this study. RA patients were subjected to a full assessment of medical and rheumatological history, and examination as well as routine lab tests. Patients and controls underwent thyroid function testing including thyroid antibodies. Patients’ disease activity was determined using the Modified Disease Activity Score and their functional status was assessed using the Modified Health Assessment Questionnaire. The most common thyroid dysfunction was hypothyroidism, which was found in 36 (24%) RA patients, followed by subclinical hypothyroidism in six (4%) patients, whereas subclinical hyperthyroidism was present in two (1.3%) patients. Autoimmune thyroid disease was present in 10 (6.6%) patients and absent in the controls. There was a significant positive correlation between thyroid stimulating hormone levels and RA disease activity parameters. Hypothyroidism was the most common thyroid disorder associated with RA, present in 24%, with a significant association with RA disease activity parameters.

Interleukin‐1 receptor antagonist gene polymorphism and hepcidin in rheumatoid arthritis: Correlations with clinical and laboratory indices of disease activity

Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is manifested as an inflammatory polyarthritis. Authors aimed to analyze the relationship between serum hepcidin, 25 amino acid protein, concentration and the anemia profiles of RA and to estimate whether it could reflect the disease activity of RA. Also, this study was conducted to explore the linkage between interleukin-1 (IL-1) receptor antagonist gene (IL-1RN) polymorphism, proinflammatory cytokine, and RA. One hundred and eighty five RA patients were enrolled in the study. For all, the following criteria were measured: RA disease activities, anemia profiles, serum concentration of hepcidin using enzyme-linked immunosorbent assay, and DNA samples were used to study genotypes of IL-1RN gene by polymerase chain reaction. Mean concentration of serum pro-hepcidin was (93.6 ± 31.5 ng/mL) in 185 RA patients. An increased frequency of the IL-1RN*1 and IL-1RN*2 alleles was relative to active RA (DAS28 > 5.1) than those with inactive to moderate RA (DAS28 ≤ 5.1). Both hepcidin and IL-1RN gene showed significant correlation with each other as well with RA disease activity parameters and anemia profile. IL-1RN gene was significantly correlated with laboratory anemia profile apart from transferritin. There was a significant difference among pro-hepcidin concentration and IL-1RN frequency regarding patients with anemia of chronic disease and those without. In conclusion, both serum concentration of pro-hepcidin and IL-1RN genotypes frequency reflect the disease activity, regardless of the anemia states in RA patients, thus they may be another potential markers for disease activity of RA.

Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis.

Methotrexate (MTX) is a disease modifying antirheumatic drug (DMARD) used as a first line agent for treating rheumatoid arthritis (RA). Pharmacologically, it is classified as an antimetabolite due to its antagonistic effect on folic acid metabolism. Many patients treated with MTX experience mucosal, gastrointestinal, hepatic or haematologic side effects. Supplementation with folic or folinic acid during treatment with MTX may ameliorate these side effects. To identify trials of supplementation with folic acid or folinic acid during MTX therapy for rheumatoid arthritis and to assess the benefits and harms of folic acid and folinic acid (a) in reducing the mucosal, gastrointestinal (GI), hepatic and haematologic side effects of MTX, and (b) whether or not folic or folinic acid supplementation has any effect on MTX benefit. We originally performed MEDLINE searches, from January 1966 to June 1999. During the update of this review, we searched additional databases and used a sensitive search strategy designed to retrieve all trials on folic acid or folinic acid for rheumatoid arthritis from 1999 up to 2 March 2012. We selected all double-blind, randomised, placebo-controlled clinical trials (RCTs) in which adult patients with rheumatoid arthritis were treated with MTX (at a dose equal to or less than 25 mg/week) concurrently with folate supplementation. In this update of the review we only included trials using 'low dose' folic or folinic acid (a starting dose of ≤ 7 mg weekly). Data were extracted from the trials, and the trials were independently assessed for risk of bias using a predetermined set of criteria. Six trials with 624 patients were eligible for inclusion. Most studies had low or unclear risk of bias for key domains. The quality of the evidence was rated as 'moderate' for each outcome as assessed by GRADE, with the exception of haematologic side effects which were rated as 'low'. There was no significant heterogeneity between trials, including where folic acid and folinic acid studies were pooled.For patients supplemented with any form of exogenous folate (either folic or folinic acid) whilst on MTX therapy for rheumatoid arthritis, a 26% relative (9% absolute) risk reduction was seen for the incidence of GI side effects such as nausea, vomiting or abdominal pain (RR 0.74, 95% CI 0.59 to 0.92; P = 0.008). Folic and folinic acid also appear to be protective against abnormal serum transaminase elevation caused by MTX, with a 76.9% relative (16% absolute) risk reduction (RR 0.23, 95% CI 0.15 to 0.34; P < 0.00001), as well as reducing patient withdrawal from MTX for any reason (60.8% relative (15.2% absolute) risk reduction, RR 0.39, 95% CI 0.28 to 0.53; P < 0.00001).We analysed the effect of folic or folinic acid on the incidence of stomatitis / mouth sores, and whilst showing a trend towards reduction in risk, the results were not statistically significant (RR 0.72, 95% CI 0.49 to 1.06)It was not possible to draw meaningful conclusions on the effect of folic or folinic acid on haematologic side effects of methotrexate due to small numbers of events and poor reporting of this outcome in included trials.It does not appear that supplementation with either folic or folinic acid has a statistically significant effect on the efficacy of MTX in treating RA (as measured by RA disease activity parameters such as tender and swollen joint counts, or physician's global assessment scores). The results support a protective effect of supplementation with either folic or folinic acid for patients with rheumatoid arthritis during treatment with MTX.There was a significant reduction shown in the incidence of GI side effects, hepatic dysfunction (asmeasured by elevated serum transaminase levels) as well as a significant reduction in discontinuation of MTX treatment for any reason. A trend towards a reduction in stomatitis was demonstrated however this did not reach statistical significance.This updated review with its focus on lower doses of folic acid and folinic acid and updated assessment of risk of bias aimed to give a more precise and more clinically relevant estimate of the benefit of folate supplementation for patients with rheumatoid arthritis receiving methotrexate.

Tumor markers are elevated in patients with rheumatoid arthritis and do not indicate presence of cancer

To investigate serum levels of tumor markers in patients with rheumatoid arthritis (RA) and their association with disease activity or the presence of cancer. We performed an observational cohort study including 100 patients with RA and control subjects. Serum levels of tumor markers carcinoembryonic antigen (CEA), cancer antigen (CA) 125, CA 19-9 and CA 15-3 were evaluated along with clinical and laboratorial RA data. Association tests between tumor markers levels and RA disease activity parameters were performed. Patients with abnormal tests were submitted to further investigation, including chest X-ray, colonoscopy, abdominal ultrasonography, upper gastrointestinal endoscopy and mammography, depending on the type of tumor marker that was elevated. Patients with RA had high levels of CEA and CA 19-9 more frequently than controls (P < 0.05). No correlation was found between tumor markers and RA disease activity assessed by the Disease Activity Score 28. Two neoplasms were found, but only one was related to high tumor marker (an ovarian carcinoma with high CA 125 levels). High tumor markers were frequently found in RA patients, even with controlled disease and were not related to actual cancer. Therefore, small increases of these markers in RA cases probably do not warrant a search for an occult neoplasm.

Soluble HLA-DR antigen levels in serum correlate with rheumatoid arthritis disease activity and the presence of disease-associated epitopes.

We investigated correlations between soluble HLA-DR (sHLA-DR) molecules and several clinical, biological and genetic parameters associated with rheumatoid arthritis (RA) disease activity. Serum sHLA-DR concentrations were determined in 146 samples from 89 RA patients by an ELISA format, using an antibody combination of mouse and rat monoclonal anti-human HLA-DR antibodies. The mean sHLA-DR serum level in RA patients was significantly increased with 277+/-19 ng/ml compared to 142+/-13 ng/ml of 80 healthy controls (P<0.001). In ascending order of significance, correlations were found between serum sHLA-DR and EULAR swelling and pain scores, Waaler-Rose, RA factor, ESR and CRP (P=0.025 to P<0.001). High sHLA-DR levels were defined above 374 ng/ml that was the 95% confidence interval of the controls. Thirty-seven blood samples (25%) in 31 RA patients were above this level. The EULAR pain and swelling scores, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and RA factor were higher (P=0.044 to P<0.001) at the moment of high sHLA-DR concentrations, compared to the lower concentrations. Higher disease activity was further found in groups of RA patients respectively heterozygous or homozygous for the disease-associated epitope (Q)R/KRAA within the HLA-DRB1 chain, compared to the group without this epitope (P<0.017 for part of the results). Likewise, sHLA-DR was respectively 169+/-17 (no disease associated epitope), 324+/-34 (heterozygous) and 442+/-69 ng/ml (homozygous for the disease-associated epitope on HLA-DRB1 alleles) (P<0.017). In conclusion, this study shows significant correlations between serum sHLA-DR levels and RA disease activity parameters, as well as increased sHLA-DR in patients with disease-associated epitope on HLA-DRB1 alleles.

Elevated serum transcobalamin levels in anaemia of rheumatoid arthritis: correlation with disease activity but not with serum tumour necrosis factor alpha and interleukin 6.

Transcobalamin (TCII) and haptocorrins (TCI and III), tumour necrosis factor alpha (TNF), interleukin-6 (IL6) and parameters of disease activity were assessed in 20 rheumatoid arthritis (RA) patients without anaemia and 19 subjects with anaemia of chronic disease (ACD) in order to determine if there was a possible correlation between these parameters. TCII, TNF and IL6 correlated positively with RA disease activity parameters, whereas their serum levels were higher in the ACD patients. TC levels were not correlated with cytokine levels. Vitamin B12 serum levels were lower in ACD. We conclude that in RA, elevated serum TCII levels are possibly mediated by increased RA disease activity, but probably not by actions of TNF or IL6. Increased TCII levels found in ACD may be explained by the higher degree of RA activity in these patients, and could also be viewed as a compensatory reaction to anaemia or reduced vitamin B12 levels. However, these preliminary findings require further confirmation.