Rheumatoid Arthritis Status Research Articles

Effects of tofacitinib therapy on arginine and methionine metabolites in association with vascular pathophysiology in rheumatoid arthritis: A metabolomic approach.

Rheumatoid arthritis (RA) has been associated with changes in lipid, arginine and NO metabolism with increased cardiovascular (CV) risk. The aim of this study is to evaluate the effect of tofacitinib, a Janus kinase (JAK) inhibitor, on arginine and methionine metabolism in correlation with inflammation, functional and pathological vascular changes during one-year treatment of patients with RA. Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound at baseline and after 6 and 12 months. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels at these time points. Twenty-six patients (13 on each arm) completed the study. CRP, ESR and DAS28 decreased significantly during one-year treatment with tofacitinib. Arginine and ADMA showed a negative univariate correlation with CRP but not with FMD, PWV or IMT. Tofacitinib at 10 mg bid significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. ADMA and SDMA levels did not change in our study. Methionine showed negative correlation with FMD at baseline and positive correlation with PWV after 12 months. No change was observed in FMD and PWV but a significant increase was measured in IMT at 6 and 12 months. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with anti-CCP after one-year treatment. With respect to vascular pathophysiology, only PWV and methionine correlated with each other. One-year tofacitinib treatment suppressed systemic inflammation and improved functional status in RA. FMD, PWV have not been affected by one-year tofacitinib treatment., while IMT increased further despite treatment. Increased arginine and methionine might contribute to the anti-inflammatory effects of tofacitinib. Increased arginine availability with no changing ADMA may protect FMD and PWV from deterioration. The increase of IMT in the anti-inflammatory environment cannot be explained by arginine or methionine metabolism in this study.

Scientific Knowledge of Rheumatoid Arthritis: A Bibliometric Analysis from 2011 to 2020.

BackgroundRecently, research on rheumatoid arthritis (RA) has made rapid progress and grown rapidly. It is a challenge to comprehensively understand RA research and hotspots. The aim of this study was to explore the current status and research trends of RA through bibliometric analysis and to provide directions for future development.MethodsPublications on RA from 2011 to 2020 were retrieved from the Web of Science Core Collection database (WoSCC). VOSviewer, CiteSpace and online bibliometric platform were used to analyze publication characteristics, including countries, institutions, journals, authors, core references, and keywords.ResultsA total of 17,037 publications were included. The publications steadily increased over the 10 years. The United States (3648 publications), with the largest proportion of publications and citations, was the largest contributor. Karolinska Institutet (508) and Annals of the Rheumatoid Disease (763) were the most active institution and journal, respectively. Emery P (193) and Tanaka Y (193) were the most prolific authors, and Smolen JS ranked first among the cited authors. The most cited reference focused on recommendations for the management of RA with synthetic and biological disease-modifying antirheumatic drugs. A co-occurrence network analysis revealed four highly connected clusters of keywords in RA research, including etiology, pathology, prognosis, biomarkers and treatment of RA.ConclusionThe present study shows a systematic and comprehensive overview of the RA-related research in the past 10 years. Clinical trials on the long-term efficiency and safety of JAK inhibitors and other novel targeted drugs may be the potential research directions for future study in this field.

Examining the Relationship Between Rheumatoid Arthritis, Multimorbidity, and Adverse Health-Related Outcomes: A Systematic Review.

Multimorbidity (the coexistence of two or more long-term conditions) is highly prevalent in people who have rheumatoid arthritis (RA). The present work systematically reviewed the literature to determine the effect of multimorbidity on all-cause mortality, functional status, and quality of life in RA. Six electronic databases were searched: CINAHL, The Cochrane Library, Embase, Medline, PsycINFO, and Scopus. Full-text longitudinal observational studies in English were selected. Quality appraisal of studies was undertaken using the Cochrane-developed QUIPS tool and a narrative synthesis of findings conducted. The search strategy identified 5,343 articles, with 19 studies meeting the inclusion criteria. Nine studies had mortality as an outcome, 9 reported functional status and/or quality of life, and 1 study reported both mortality and functional status. The number of participants ranged from 183 to 18,485, with studies conducted between 1985 and 2018. The mean age of participants ranged from 52.0 to 66.6 years, and 60.0-88.0% were female. Nine studies showed a significant association between multimorbidity and higher risk of mortality in people with RA. Ten studies reported significant associations between multimorbidity and reduced functional status in RA. Three studies also showed a further association with reduced quality of life. Only one study investigated the influence of mental health comorbidities on outcomes. Our review findings indicate that multimorbidity is a significant predictor for higher mortality and poorer functional status/quality of life in people with RA and should be considered in clinical management plans.

Association between Rheumatoid Arthritis and Poor Self-Perceived Oral Health in Korean Adults.

Background and objective: Rheumatoid arthritis (RA) and oral health problems have been reported as specific disease units; however, this study was conducted to evaluate the association between RA and comprehensive oral health status. Therefore, this study aimed to assess the association between RA and oral health using self-perceived oral health (SPOH) variables that can determine the oral health status in Korean adults using representative national data. Methods: Data from 40,186 selected participants were collected from the Korea National Health and Nutrition Examination Survey (KNHANES) between 2007 and 2018. The prevalence relative risk (PRR) was estimated using Poisson regression analysis to obtain the risk ratio of the SPOH according to RA. Results: The risk of SPOH depending on the RA status was statistically significant (odds ratio [OR] = 1.108, 95% confidence interval [CI] 1.005–1.222). In addition, the risk of SPOH depending on the RA status was higher in the group with diabetes mellitus (DM) (OR = 1.205, 95% CI 0.966–1.503) than in the group without DM (OR = 1.088, 95% CI 0.976–1.214). Conclusions: In this study, a significant association was identified between RA and SPOH. Oral health experts should identify the factors affecting the oral health of patients with RA and provide correct oral health care; however, additional research is needed.

Investigation of the correlation between mood disorder symptoms and disease activity and functional status in rheumatoid arthritis patients

To investigate the correlation between depressive-anxiety symptoms, mixed features, disease activity, and functional status in patients with rheumatoid arthritis (RA) in the light of the shared underlying etiology in both disorders. The study included 556 patients with RA. RA disease activity was measured using the Disease Activity Score 28-joint count C reactive protein (DAS28-CRP), and the patients were evaluated by a Health Assessment Questionnaire (HAQ). The Hospital Anxiety and Depression Scale (HADS), Mood Disorder Questionnaire (MDQ), and Modified Hypomania Checklist (mHCL) were used to evaluate the mixed depression and bipolarity status of the patients. Of the patients, 430 (77.3%) were female and 126 (22.7%) were male. The median age was 57 years, the median HAQ score was 0.55 points, and the median DAS28-CRP score was 4.1 points. The evaluation of the patients by DAS28-CRP revealed that 58.5% of the patients had moderate and severe disease activity, while only 23.4% of them were in remission. The group using the combination of synthetic disease-modifying anti-rheumatic drugs (sDMARD) and steroid therapy had significantly higher HAD-depression, HAD-anxiety, mHCL, DAS28-CRP, HAQ, and MDQ scores than the group using sDMARD alone. The grouping of the patients based on the DAS28-CRP cut-off scores showed that the patients with moderate and severe disease activity had significantly higher HADS, mHCL, MDQ scores than those in remission and those with mild disease activity (p < 0.001). Disease severity and functional status in RA can be affected by comorbid anxiety-depressive and mixed symptoms. Therefore, clinicians should consider screening the depressive-anxiety and mixed mood symptoms of RA patients. Moreover, patients who use steroid therapy are more susceptible to mood symptoms (anxiety, depression, bipolarity), which should also be considered during the follow-up of patients.

Investigation of the correlation between mood disorder symptoms and disease activity and functional status in rheumatoid arthritis patients.

To investigate the correlation between depressive-anxiety symptoms, mixed features, disease activity, and functional status in patients with rheumatoid arthritis (RA) in the light of the shared underlying etiology in both disorders. The study included 556 patients with RA. RA disease activity was measured using the Disease Activity Score 28-joint count C reactive protein (DAS28-CRP), and the patients were evaluated by a Health Assessment Questionnaire (HAQ). The Hospital Anxiety and Depression Scale (HADS), Mood Disorder Questionnaire (MDQ), and Modified Hypomania Checklist (mHCL) were used to evaluate the mixed depression and bipolarity status of the patients. Of the patients, 430 (77.3%) were female and 126 (22.7%) were male. The median age was 57 years, the median HAQ score was 0.55 points, and the median DAS28-CRP score was 4.1 points. The evaluation of the patients by DAS28-CRP revealed that 58.5% of the patients had moderate and severe disease activity, while only 23.4% of them were in remission. The group using the combination of synthetic disease-modifying anti-rheumatic drugs (sDMARD) and steroid therapy had significantly higher HAD-depression, HADanxiety, mHCL, DAS28-CRP, HAQ, and MDQ scores than the group using sDMARD alone. The grouping of the patients based on the DAS28-CRP cut-off scores showed that the patients with moderate and severe disease activity had significantly higher HADS, mHCL, MDQ scores than those in remission and those with mild disease activity (p < 0.001). Disease severity and functional status in RA can be affected by comorbid anxiety-depressive and mixed symptoms. Therefore, clinicians should consider screening the depressive-anxiety and mixed mood symptoms of RA patients. Moreover, patients who use steroid therapy are more susceptible to mood symptoms (anxiety, depression, bipolarity), which should also be considered during the follow-up of patients.

Dental and temporomandibular joint alterations in rheumatoid arthritis patients and their association with salivary oxidative stress

Background/aim Rheumatoid arthritis (RA) is the most extensive inflammatory arthritis causing permanent deformities in the joint. Increasing evidence suggests that oxidative stress is a substantial factor in the pathogenesis of RA. This study aimed to examine the salivary oxidant-antioxidant status of RA and control groups and to compare these biomarkers by correlating them with disease activity, acute phase reactants, and clinical findings.Materials and methods Age and sex-matched 60 participants including 30 patients with RA and 30 control (50 females, 10 males; mean age: 42.62 ± 10.89 years) were evaluated. RA disease activity and severity were evaluated by the disease activity score 28-C reactive protein (DAS 28-CRP). Rheumatoid factor (RF) positivity, anticitrullinated protein antibodies (ACPA) positivity, erythrocyte sedimentation rate (ESR), CRP, tender and swollen joint counts, and medical treatment regimens of the patients (glucocorticoids, conventional or biologic disease-modifying antirheumatic drugs) were recorded. In the radiographic examination, dental findings, and bone alterations of the temporomandibular joint (TMJ) were recorded and compared for both groups. Saliva samples were obtained for analysis of total antioxidant status (TAS), total oxidant status (TOS), arylesterase (ARE), and oxidative stress index (OSI) levels. The data analysis was conducted by independent sample t-test and chi-square test.Results Condylar erosion was the most common radiographic change in TMJ of RA patients. Osteophyte formation was a prominent finding in the control group. Lower TAS and higher OSI levels were found in RA patients compared with controls (p = 0.013; p = 0.029, respectively). The effect of DAS 28-CRP score on the levels of oxidative stress biomarkers in RA patients was not significant. Conclusion Oxidative stress causes tissue damage in response to excessive mechanical loading, which in turn promotes TMD. However, disease activity has not a prominent impact on the salivary oxidative stress status of RA patients.

No association between rheumatoid arthritis and cognitive impairment in a cross-sectional national sample of older U.S. adults

BackgroundStudies suggest an increased prevalence of cognitive impairment (CI) among people with rheumatoid arthritis (RA). However, most prior studies have used convenience samples which are subject to selection biases or have failed to adjust for key confounding variables. We thus examined the association between CI and RA in a large national probability sample of older US adults.MethodsData were from interviews with 4462 participants in the 2016 wave of the nationally representative U.S. Health and Retirement Study with linked Medicare claims. RA diagnoses were identified via a minimum of two ICD-9CM or ICD-10 codes in Medicare billing records during the prior 2 years. The Langa-Weir Classification was used to classify cognitive status as normal, cognitively impaired non-dementia (CIND), or dementia based on a brief neuropsychological battery for self-respondents and informant reports for proxy respondents. We compared the odds of CI between older adults with and without RA using logistic regression, adjusted for age, education, gender, and race.ResultsMedicare records identified a 3.36% prevalence of RA (150/4462). While age, gender, education, and race independently predicted CI status, controlling for these covariates we found no difference in CI prevalence according to RA status (prevalent CI in 36.7% of older adults with RA vs. 34.0% without RA; adjusted OR = 1.08, 95% CI 0.74–1.59, p = .69).ConclusionThere was no association between RA and CI in this national sample of older U.S. adults.

Phenotype of Platelet Is Altered and Associated with Disease Activity of Rheumatoid Arthritis

Platelets play a major role in the hemostasis physiologically through their activation. Activated platelets acquire functional abilities such as adhesion, morphological changes, and releasing humoral factors or microparticles (MPs). Recent reports have been shown that platelets and MPs include unique humoral factors such as chemokines and cytokines. We hypothesized that platelets and MPs can be vectors for transferring these factors to the lesions through circulation and contribute to disease processes of systemic diseases. To clarify the role of platelets in the pathogenesis of connective tissue diseases (CTDs), especially in rheumatoid arthritis (RA), we examined the phenotype and activation status of circulating platelets and the association with clinical characteristics.Fifty-seven patients with RA were involved and 21 systemic sclerosis (SSc), which has different characteristic compared to RA in CTDs, and 16 healthy individuals (HI) were examined as controls. Platelet rich plasma was used to detect fractions of platelets and MPs by flow cytometry. Fraction of platelets and MPs were defined by the size using standardized Megamix® beads. For the phenotypic analysis of platelets, surface expression of CD62P (P-selectin), membrane-bound TGF (transforming growth factor)-beta, CD147 (emmprin), CD142 (tissue factor), CD31 (platelet endothelial cell adhesion molecule (PECAM)-1) on CD41+CD45-CD14- platelets was examined. For the activation status of platelets, the ratio of CD62P or PAC1-positive to -negative platelets for the activation and the ratio of MPs to platelets as a marker for the release of MPs. Clinical parameters at blood drawing were retrospectively obtained and correlation was examined.We first examined the phenotype of circulating platelets in RA and controls to have a general picture of the difference. Proportion of CD62P+ platelets were higher in both RA and SSc compared to HI (0.054 ± 0.032, 0.060 ± 0.030 versus 0.021 ± 0.006, P = 0.0005, P < 0.0002, respectively). Interestingly, CD147+ platelets were significantly higher in RA (0.61 ± 0.05 versus 0.29 ± 0.01, P = 0.0004), whereas not only proportion of CD147+ platelets (0.69 ± 0.11) but that of TGF-beta+ platelets (0.073 ± 0.021 versus 0.014± 0.006) were higher in SSc compared to healthy controls (P = 0.0001, P = 0.0001, respectively). Thus, phenotype of platelets is altered in RA compared to HI or SSc. Then, we focused on RA and activation status of circulating platelets was further examined by expression of activation markers and release of MPs. Proportion of activated platelets such as CD62P (0.047 ± 0.041 versus 0.012 ± 0.007) and PAC1 (0.075 ± 0.072 versus 0.013 ± 0.011) and that of MPs (0.034 ± 0.06 versus 0.21 ± 0.03) were higher in RA compared to HI (P < 0.001, P < 0.004, P < 0.00001, respectively). In patients with RA, proportion of activated platelets (CD62P+ or PAC1+ platelets) and that of MPs were correlated each other (r = 0.57, P < 0.0001; r = 0.36, P < 0.004, respectively). When activation status of platelets was compared to clinical parameters, ratio of CD62P+ platelets and that of MPs were positively correlated with clinical parameters associated with disease activity of patients with RA, such as serum CRP (r = 0.36, P < 0.006 and r = 0.29, P < 0.03), erythrocyte sedimentation rate (r = 0.31, P < 0.02 and r = 0.35, P < 0.009) and composite disease markers such as Simplified Disease Activity Index (SDAI) (r = 0.28, P < 0.04 and r = 0.31, P < 0.02) and Clinical Disease Activity Index (CDAI) (r = 0.28, P < 0.04 and r = 0.32, P < 0.02), but interestingly, there was no correlation between proportion of PAC1+ platelets and clinical parameters. No correlation was observed with age, sex, HAQ-DI, nor MMP-3. Furthermore, six patients with RA who were in active phase and treated with methotrexate and/or biologics and achieved improvement of disease activity at 12 week after the treatment were compared. The ratio of CD62+ platelets and that of MPs were decreased along with the improvement of disease. (P < 0.03, P < 0.03, respectively).In conclusion, circulating platelets in RA were activated and their activation status is correlated with the inflammatory markers and disease activity, suggesting that circulating platelets reflects and can contribute to the process of systemic chronic inflammation in RA. Phenotype of platelets can be a novel biomarker for the disease. DisclosuresNo relevant conflicts of interest to declare.

AB0277 ASSOCIATION BETWEEN INTRA-ERYTHROCYTE METHOTREXATE POLYGLUTAMATE CONCENTRATION AND CLINICAL RESPONSE IN RHEUMATOID ARTHRITIS IN PATIENTS TREATED WITH METHOTREXATE INJECTABLE SUBCUTANEOUSLY

Background:Methotrexate (MTX) is the first-line treatment for rheumatoid arthritis (RA). Due to its short half-life, blood MTX dosage is not performed in current practice. Erythrocyte MTX-polyglutamate (MTX-PG), which penetrates into the red blood cells, would be correlated with the area under the MTX curve and would be more accessible for dosing. When treatment is initiated, its concentration correlates with efficacy and therapeutic adherence.Objectives:To determine the interest of erythrocyte MTX-PG dosage in case of failure of 1st line MTX treatment.Methods:In this single-centre cross-sectional study, RA patients presenting for consultation at the Saint-Etienne University Hospital, with a stable dose of MTX for more than 3 months at least 15 mg/week subcutaneously with either clinical remission (DAS28&lt;2.6) or active disease (DAS28&gt;3.2) were included between July 2nd 2018 and May 28th 2020. In order to assess therapeutic compliance, the patient completed the compliance questionnaire of Rheumatology (CQR) questionnaire. The determination of erythrocytic MTX-PG was performed on a 5 mL blood sample by liquid chromatography method for the determination of the different PG forms.Results:Sixty patients were included, 34 in the active RA group and 26 in the RA group in remission. One patient withdrew his consent. Only 16% of patients were observed with a CQR score &gt; 80%. Patients in remission were leaner with a longer duration of disease and MTX treatment. The sex ratio, RA status, creatinine clearance and MTX dose was not different in both groups. The CQR was better in the remission group than in the active RA group. However, total MTX-PG was not different in the two groups. The same results were observed for the different forms of MTX-PG 1, 2, 3 or 4. In contrast, in the remission PR group, total MTX-PG or MTX-PG2, 3, 4 and 5 correlated inversely with BMI while MTX-PG3 correlated positively with BMI in the active PR group. In the active PR group, MTX-PG5 correlated with MTX dose.Conclusion:MTX-PG dosage is not a biomarker of good response to MTX in our study. However, compliance is a key factor to be considered in RA with active disease in adapting patient management.

Subgingival microbiome of deep and shallow periodontal sites\xa0in patients with rheumatoid arthritis: a pilot study

BackgroundSubgingival microbiome in disease-associated subgingival sites is known to be dysbiotic and significantly altered. In patients with rheumatoid arthritis (RA), the extent of dysbiosis in disease- and health-associated subgingival sites is not clear.Methods8 RA and 10 non-RA subjects were recruited for this pilot study. All subjects received full oral examination and underwent collection of subgingival plaque samples from both shallow (periodontal health-associated, probing depth ≤ 3mm) and deep subgingival sites (periodontal disease-associated, probing depth ≥ 4 mm). RA subjects also had rheumatological evaluation. Plaque community profiles were analyzed using 16 S rRNA sequencing.ResultsThe phylogenetic diversity of microbial communities in both RA and non-RA controls was significantly higher in deep subgingival sites compared to shallow sites (p = 0.022), and the overall subgingival microbiome clustered primarily according to probing depth (i.e. shallow versus deep sites), and not separated by RA status. While a large number of differentially abundant taxa and gene functions was observed between deep and shallow sites as expected in non-RA controls, we found very few differentially abundant taxa and gene functions between deep and shallow sites in RA subjects. In addition, compared to non-RA controls, the UniFrac distances between deep and shallow sites in RA subjects were smaller, suggesting increased similarity between deep and shallow subgingival microbiome in RA. Streptococcus parasanguinis and Actinomyces meyeri were overabundant in RA subjects, while Gemella morbillorum, Kingella denitrificans, Prevotella melaninogenica and Leptotrichia spp. were more abundant in non-RA subjects.ConclusionsThe aggregate subgingival microbiome was not significantly different between individuals with and without rheumatoid arthritis. Although the differences in the overall subgingival microbiome was driven primarily by probing depth, in contrast to the substantial microbiome differences typically seen between deep and shallow sites in non-RA patients, the microbiome of deep and shallow sites in RA patients were more similar to each other. These results suggest that factors associated with RA may modulate the ecology of subgingival microbiome and its relationship to periodontal disease, the basis of which remains unknown but warrants further investigation.

P130 The relationship between antinuclear antibodies and erosive disease in patients with rheumatoid arthritis

Abstract Background/Aims The effects of antinuclear antibodies (ANA) in rheumatoid arthritis (RA) are not fully characterised. Studies investigating the effect of ANA on disease activity in RA have yielded mixed results. The presence of ANA has been correlated with higher levels of CRP and joint inflammation in RA. Evidence suggests that ANA positivity at baseline may predict poor response to both traditional disease modifying agents and biologic therapy. ANA may also be associated with higher incidences of ocular disease, Felty’s syndrome, vasculitis and subjective pain in RA patients. On the other hand, other studies showed a lack of correlation between ANA status and joint inflammation in RA. Our study investigates the relationship between ANA positivity and joint erosions in rheumatoid patients. Methods This is a cross-sectional study of patients attending the early arthritis clinic at Northwick Park Hospital in London over a five year period (2014-2019). A total of 631 patients were identified of whom 261 had RA. We collected data on the age, gender, ANA positivity, the presence of anti-CCP (anti cyclic-citrullinated peptide) antibodies and rheumatoid factor (RF) at presentation as well as the presence of erosive disease on radiological reports of hand X-rays. Positive ANA was defined as having a titre of 1:80 or greater. Patients with missing ANA result or hand X-ray reports were excluded, leaving 228 patients. Two-tailed Chi-square tests for categorical data and two-tailed student’s t-tests for continuous data were performed to determine the statistical significance of comparisons made between the ANA positive and negative groups. Results Of the 228 patients, 49 (21.5%) were male and 179 (78.5%) were female. The mean age was 58 years. 84 (36.8%) patients were ANA positive (group 1) and 144 (63.2%) were ANA negative (group 2). In group 1, 23/84 (27.4%) patients had erosive disease. In group 2, erosions were found in 25/144 patients (17.4%). This difference was not statistically significant (p = 0.073). The number of patients who were RF positive in groups 1 and 2 were 79.5% and 73.6% respectively (p = 0.317); 75/84 (89.3%) patients in group 1 and 113/143 (79.0%) in group 2 were anti-CCP antibody positive (p = 0.048). The means of the age of patients were 53 and 62 years in group 1 and group 2 respectively (p &amp;lt; 0.0001); the ANA positive group was significantly younger. The male:female ratio was 13:71 in group 1 and 36:108 in group 2 (p = 0.091). Conclusion Our study showed no significant association between ANA status and erosive disease in RA, although a greater proportion of patients had erosions in the ANA positive group. Larger observational studies may better study this relationship. Disclosure T. Guruparan: None. M. Hutchinson: None. R. Hayward: None. H. Penn: None. P. Kalia: None.

Altered Antibody Response to Epstein-Barr Virus in Patients With Rheumatoid Arthritis and Healthy Subjects Predisposed to the Disease. A Twin Study.

Objectives: To study Epstein-Barr virus (EBV) antibody patterns in twin individuals with rheumatoid arthritis (RA) and their healthy co-twins, and to determine the heritability of antibody responses against the EBV encoded EBNA1 protein.Methods: Isotypes of EBNA1 antibodies were measured in 137 RA affected- and 150 healthy twin pairs. We estimated the effect of RA and RA predisposition, anti-citrullinated antibodies (ACPA), IgM rheumatoid factor (RF), the shared epitope (SE) and the PTPN22-T allele (PTPN22) on the level of EBNA1 antibodies. We also determined the heritability of EBNA1 antibody levels.Results: IgA-EBNA1 antibody levels were increased in twins from RA discordant twin pairs irrespective of RA, ACPA or IgM-RF status. The IgG-EBNA1 antibody level was elevated in healthy co-twins from RA discordant twin pairs but not in RA affected twins. The IgM-EBNA1 antibody level was elevated in both RA twins and their healthy co-twins. The effect of RA on the IgA-EBNA1 antibody level was reversed when SE was present and with no effect of PTPN22. The heritability of IgA-, IgG- and IgM-EBNA1 antibody level was 40.6, 65.5, and 54.3%, with no effect of environment shared by the twins.Conclusion: EBNA1 antibody levels are distinctively different between patients with RA and healthy subjects but also between relatives of RA strongly predisposed to RA and healthy subjects. The high level of IgA EBNA1 antibodies associated with RA and a family predisposition to RA is attributable to both genetics incl. the shared epitope and environmental variation.

Reduced cardiorespiratory fitness is a mediator of excess all-cause mortality in rheumatoid arthritis: the Trøndelag Health Study

ObjectivesInvestigate if low cardiorespiratory fitness (CRF) was associated with and acted as a mediator of excess all-cause mortality rate in persons suffering from rheumatoid arthritis (RA) compared with the general...

Oral Hygiene Status in Rheumatoid Arthritis Patients and Related Factors.

Objectives:To evaluate oral hygiene status in Rheumatoid arthritis (RA) patients, to analyse possible related factors, and to investigate the role of the rheumatologist in information about importance of adequate oral hygiene status in RA patients.Methods:A cross-sectional study that included 100 consecutive RA patients (89% female, mean age 46.7 ± 11.7 years). For each patient, we recorded oral symptoms, oral hygiene status and role of rheumatologist in information on the oral hygiene status. Factors associated with regular brushing (≥2/day) were also analysed.Results:Median disease duration was 8 years (4;2). Dental pain was reported by 74% of patients and bleeding by 51% of them. Regular brushing was noted in 45% of patients. The use of a correct brushing method was noted in 14% of cases. Two patients reported visiting a dentist regularly. Information explaining that poor oral hygiene has a negative impact on RA was delivered by rheumatologist to 11 patients. Regular brushing of teeth was recommended by rheumatologist to 8 patients and 10 patients were advised by their rheumatologist to consult a dentist. Regular brushing was more important in women (48,3% vs 18,2%; p=0.05) and in the literate patients (57,6 vs 31,2%, p<0.01). No association was found between regular brushing, Disease Activity Score 28 (DAS28) and health Assessment Questionnaire (HAQ).Conclusion:This study illustrates bad oral hygiene status in RA patients, which seems more important in men and illiterate patients. It also highlights poor information given by the rheumatologist.

The Influence of Menopause and Inflammation on Redox Status and Bone Mineral Density in Patients with Rheumatoid Arthritis.

Although oxidative stress is considered to be one of the key pathogenic factors in rheumatoid arthritis (RA), there is insufficient knowledge regarding the impact of menopause on redox status in this population. Thus, this study is aimed at assessing the influence of menopause within healthy women and within RA patients as well as the impact of RA in premenopausal and postmenopausal women on redox status, with special reference to bone mineral density (BMD). A total of 90 women were included in the study, 42 with RA and 48 age-matched healthy controls. They were divided into subgroups according to the presence of menopause. Following oxidative stress parameters were measured spectrophotometrically: index of lipid peroxidation (measured as TBARS), nitrites (NO2−), superoxide anion radical (O2−), hydrogen peroxide (H2O2), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). BMD was assessed by using a dual-energy X-ray absorptiometry scanner. Comorbidities and drug history were recorded. The levels of H2O2 and TBARS were elevated in patients with RA, while NO2− and O2− increased in healthy women, both in premenopausal and postmenopausal groups. SOD activity decreased in postmenopausal RA patients. BMD was reduced in postmenopausal RA women. There was a correlation between NO2− and O2− with Health Assessment Questionnaire (HAQ) index in RA patients. Given that postmenopausal state was associated with elevated oxidative stress within healthy women and that menopausal state did not affect redox homeostasis within RA patients, but the redox homeostasis was altered in both RA groups compared to healthy women, it can be presumed that impaired redox status in RA occurred due to presence of the disease, irrespective of age. Moreover, menopause attenuates BMD reduction in women with RA. These results may indicate the need for therapeutic use of antioxidants in the form of supplements in women with RA, regardless of age.

Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies.

Objective:To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents.Methods:Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out.Results:A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients.Conclusion:Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.

Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis

Immune regulation status may indicate immunological remission in rheumatoid arthritis (RA). This cross-sectional study aimed to determine the Regulatory T cell (Treg) properties, together with 14 plasma cytokines levels between active RA and clinical remission patients. Peripheral blood (PB) Foxp3+ Treg was collected from RA patients for determination of Treg inhibitory activity using a co-culture system. Other PB T cell types and plasma cytokines were determined by flow-cytometry. The Treg results were analyzed according to the disease activity score-28 (DAS28). Then sensitivity and specificity were calculated for the indication of the remission status. The number and inhibitory activity of Treg are higher in the clinical remission as compared to the active RA (p value < 0.0001). Also, Treg: CD4+CD25+CD127+ cell ratio demonstrates the similar result (p value < 0.05). Treg inhibitory activity is inversely correlated with the DAS28. Specificity and positive likelihood ratio of inhibitory activity for indicating remission status are 92.31% (95% CI 63.97–99.81) and 11.14 (95% CI 1.67–74.14), respectively. Treg inhibitory activity is a promising prognostic marker and probably represents the immunological remission status in RA.

Development of Monitoring System for Assessing Rheumatoid Arthritis within 5 Minutes Using a Drop of Bio-Fluids.

Rheumatoid arthritis (RA) disease activity fluctuates over time. The disease activity score 28 (DAS28ESR) is a widely used and validated scoring system for assessing RA activity; however, it requires time and expertise. This study aimed to develop a new molecular assay capable of rapidly and objectively assessing RA activity. We used a rapid immuno-assay system (FREND™) to measure soluble CD14 (sCD14) levels, which reflect the DAS28ESR. SCD14 concentrations in urine and serum of RA patients were measured, and RA activity and responses to anti-rheumatic drugs were examined at baseline and after 6 months. FREND™ quantified sCD14 levels in a drop of serum and urine accurately and within 5 min. Serum sCD14 concentrations and its changes correlated well with disease activity and treatment responses, and the results were comparable to C-reactive protein. The new composite indices, including the DAS28CD14 and simplified DASCD14, better detected RA activity than a single sCD14 value and correlated strongly with the DAS28ESR. These indices exhibited excellent diagnostic performance for discriminating a good response 6 months after treatment. We developed a new system for assessing RA activity and therapeutic outcome within 5 min. CD14-based composite indices may have utility for accurate and frequent monitoring of RA status.

Depression and anxiety in an early rheumatoid arthritis inception cohort. associations with demographic, socioeconomic and disease features

ObjectiveDepression and anxiety are not uncommon in Rheumatoid arthritis (RA). It is increasingly recognised that they are associated with high disease activity and worse disease outcomes. We aimed to examine...