Development Of RA Research Articles

Citrullination in periodontium is associated with Porphyromonas gingivalis

ObjectiveTo analyse the citrulline level in the periodontium in association with the presence of or antibody levels against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. DesignGingival crevicular fluid (GCF), subgingival biofilm and blood serum were sampled from 98 subjects (26 with RA, 72 without RA (NoRA)). GCF was analyzed for the level of citrulline, for interleukin (IL)-1β, IL-17, IL-10 and monocyte-chemoattractant protein (MCP)-1. Microorganisms were identified in subgingival biofilms. Antibodies againstP. gingivalis, and Aggregatibacter actinomycetemcomitans were quantified in serum. ResultsGCF citrulline level was the lowest (by trend) in NoRA group without periodontitis. In NoRA, but not in RA an association between GCF citrulline level and P. gingivalis antibody levels was found and the GCF citrulline levels were higher in P. gingivalis positive samples. Any association of A. actinomycetemcomitans with GCF citrulline level did not exist. A model of univariate variance analysis (p = 0.001) showed a dependence of GCF citrulline level from the number of sites with PD (probing depth) ≥5 mm (p = 0.003) and the GCF MCP-1/CCL2 level (p = 0.019). Compared with NoRA in RA the number of teeth was lower, the number of sites with PD ≥ 5 mm was less, GCF levels of interleukin-17 and MCP-1/CCL2 were higher and those of IL-10 lower. Yeasts were only cultured in 15 RA patients (p < 0.001). ConclusionCitrullination in periodontium might be associated with P. gingivalis supporting the potential role as a trigger in the development of RA. Pathogenesis of periodontal disease in RA patients seems to differ from that in NoRA and should be investigated further.

The promoting effect of MMP13 on mediating the development of HFLS-RA by the target of miR-19a through IL-17 signaling pathway.

By investigating the expression profiles of miR-19a andmetalloproteinases (MMP13) in human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) and HFL cells lines, this study intends to confirm the directly target connection between them and reveal the effect of suppressing MMP13 on HLFS-RA migration, invasion and apoptosis. After screening the abnormal expressed messenger RNAs and microRNAs in synovial tissues of patients with RA, the underlying pathway was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The HFLS-RA cell line was transfected for the following experiments with pcDNA3.1(+) served as vector. The directly target association between miR-19a and MMP13 was confirmed by Luciferase reporter assay. Microarray analysis suggested that MMP13 was upregulated while miR-19a was downregulated in HFLS of RA tissues compared with the healthy control group. MMP13 was related to many proteins in protein-protein interaction network, which might be the main influencing factor of RA. KEGG pathway analysis identified that interleukin (IL)-17 pathway was activated in the regulation of MMP13 in the development of RA. Through observing the alteration of luciferase activity, miR-19a could indeed bind to the 3'UTR of the downstream of MMP13, the target association was then confirmed. The proliferation and invasion of HFLS-RA were promoted by overexpressing MMP13 protein. miR-19a could function as a suppressor of MMP13 and thereby retard the severity of RA. The results showed that miR-19a could regulate the expression of MMP13 in HFLS-RA by mediating the proliferation and invasion of HFLS-RA through IL-17 signaling pathway, thereby participating in the degradation of chondrocytes in the progression of RA.

EULAR definition of "arthralgia suspicious for progression to rheumatoid arthritis" in a large cohort of patients included in a program for rapid diagnosis: role of auto-antibodies and ultrasound.

To evaluate the performance of the European League Against Rheumatism (EULAR) definition of arthralgias suspicious for progression to RA in patients with hand arthralgias and to estimate the added value of both auto-antibodies and ultrasound (US) with power Doppler (PD). Consecutive patients admitted for hand arthralgias to "Reuma-check" ® program were included. This program includes the following at baseline: clinical assessment, laboratory tests, US with PD of both hands, and radiography of both hands and feet. All patients were followed-up after baseline evaluation by their treating rheumatologists, and a definitive diagnosis of RA (ACR/EULAR 2010 criteria) was established or not. A total of 465 consecutive patients were included. During follow-up, 44 (9.4%) were diagnosed with RA. Mean of baseline EULAR features describing arthralgia suspicious for progression to RA was 4.1 in patients with final diagnosis of RA vs 2.3 in non-RA patients (p < 0.0001). The AUC for the EULAR defined features describing arthralgia suspicious for progression to RA for the final diagnosis of RA was 0.7827, while adding US with PD, rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibodies (ACPA) data, the AUC was 0.9172 (p < 0.0001). In the multivariate regression logistic analysis, baseline features associated with a final diagnosis of RA were difficulty with making a fist, RF, ACPA, and US with PD. EULAR definition of arthralgia suspicious for progression to RA had an acceptable performance to predict the future development of RA and improves adding information of both RF, ACPA and US with PD data.Key Points• Clinically suspect arthralgia may trigger rheumatologists to monitor patients closely for an early diagnosis.• EULAR definition of arthralgia suspicious for progression to RA predicts future development of arthritis.• Auto-antibodies and ultrasound improve EULAR definition of arthralgia suspicious for progression to RA.

T-cell specific upregulation of Sema4A as risk factor for autoimmunity in systemic lupus erythematosus and rheumatoid arthritis

The aim of the present study was to evaluate the impact of SEMA4A genetic variants on expression of sema4A protein and its relation to autoimmunity development in Systemic Lupus Erythematosus and Rheumatoid Arthritis patients. A total of 541 SLE patients, 390 RA patients and 607 healthy individuals were genotyped. We also assessed SEMA4A mRNA expression from whole blood cells and the in vitro protein production from resting and activated T lymphocytes as well as mature dendritic cells from healthy individuals stratified according to their genotypes for SLE/RA associated SEMA4A variants. Our results showed that T/T genotype for rs3738581 SNP is associated with both RA and SLE development (p = .000053, OR = 2.35; p = .0019, OR = 2.07, respectively; statistical power = 100%) and also to an increased in vitro sema4A production in active T lymphocytes. Our findings are indicative of a T cell-specific upregulation of sema4A in the presence of T/T genotype, being a risk factor for SLE and RA.

Timing of Elevations of Autoantibody Isotypes Prior to Diagnosis of Rheumatoid Arthritis.

To evaluate patterns of elevations of isotypes of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) pre-rheumatoid arthritis (RA) diagnosis and post-RA diagnosis. Using the Department of Defense Serum Repository we identified 214 RA cases and 210 matched controls. Up to 3 pre-RA diagnosis and 1 post-RA diagnosis serum samples per subject were tested for RF and for IgA, IgG, and IgM ACPAs. The timing and trajectories of elevations of autoantibodies were evaluated. Autoantibody levels were elevated in cases versus controls a mean of 17.9 years before RA diagnosis for IgG ACPA, 14.2 years for IgA-RF, 7.2 years for IgM-RF, 6.2 years for IgA ACPA, and 5.0 years for both IgM ACPA and IgG-RF (P < 0.01 for all comparisons). There were similar relationships for positive or negative autoantibody status, with cases first showing positivity for IgG ACPA 1.9 years pre-RA and for IgA-RF 1.7 years pre-RA, followed by the other isotypes. Only IgA ACPA positivity was significantly increased in post-RA diagnosis samples (19% 0-2 years pre-RA versus 39% >2 years post-RA diagnosis; P = 0.04). All autoantibody levels demonstrated an early initial elevation, a period of stability, then an increase immediately before RA diagnosis. A pre-RA endotype of early elevation of autoantibodies was associated with increased use of biologic therapy, and a higher prevalence of sicca symptoms and lung disease post-RA diagnosis. Differences in patterns of elevations of autoantibody isotypes have implications for understanding the pathophysiology of RA development. These include understanding what factors drive initial autoantibody elevations compared to what factors (including mucosal) drive later increases in autoantibody levels and a transition to clinically apparent RA, and how pre-RA endotypes may influence post-RA diagnosis phenotypes.

Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients.

ObjectivesSmoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients.MethodsDisease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status.ResultsOf the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5–6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable.ConclusionSmoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.

Rhetorical Organization of Applied Linguistics Abstracts: Does Scopus Journal Quartile Matter?

This study investigates whether Scopus journal quartile affects the rhetorical organization and linguistic realizations of applied linguistics research article (hereafter RA) abstracts from Scopus-indexed journals. Embracing the corpus-based approach, this study analyzed 28 abstracts from four AL journals (seven abstracts each) with different quartile. Hyland’s (2000) model was adopted as the analysis guideline. The phrase was the unit of analysis to obtain fine-grained results of the moves occurrences. The analysis revealed that most of the articles from Q2-Q4 journals applied the informative typology, while those from Q1 journal applied the indicative-informative one. Journal quartile does not necessarily affect the manifestation of all moves and steps. The number of occurrences of Step 1- describing participants and Step 3- describing procedure in the Method move was similar in all journals. Moreover, the Purpose and Findings moves were obligatory in all journals. Journal quartile played an influential role in employing the verb tense of Introduction, Purpose, and Conclusion moves and the sentence voice of Method and Conclusion moves. The findings reach a conclusion that journal quartile does not necessarily affect the domination of the standard rules of the RA abstracts’ rhetorical organization and linguistic realizations in AL journals. This study provides insight into the realm of English academic writing about the current trends of move analysis from the journal quartile lens. Further comparative research on the rhetorical features between the accepted and rejected RA abstracts and materials development for the pedagogy of English for research publication purposes are recommended.

ASYMPTOMATIC URINARY TRACT INFECTION BY PROTEUS MIRABILIS IN RHEUMATOID ARTHRITIS PATIENTS

Background: Proteus mirabilis is thought to contribute in rheumatoid arthritis (RA) development in susceptible individuals through molecular mimicry mechanism. This study was detecting the prevalence of asymptomatic bacteriuria (ABU) caused by Proteus mirabilis in RA patients to shed light on its rule in RA pathogenesis. Submit Date 2019-03-25 Revise Date 2019-04-17 Accept Date 2019-04-21 Methods: This work has been conducted in medical Microbiology and Immunology Department and Rheumatology and Rehabitilation Department, Faculty of Medicine, Zagazig University, during the period from May 2017 to May 2018 over a period of 12 months. This study is a case control included 70 RA patients (66 females and 4 males), with age ranged from 25 to 65 years, and 70 healthy controls (67 females and 3 males), with age ranged from 24 to 65 years. Two consecutive urine samples one week interval were collected from each participant for urine count and culture. Blood samples were collected from each participant for detection the level of IgG antibodies against both Proteus mirabilis and E. coli (the most frequent isolated organism from the RA urine) by homely prepared ELISA. Results: The ABU was detected in (40%) of RA patients and in (4.3%) of healthy controls. The most common isolated organisms were E. coli (50%) followed by Proteus mirabilis (25%). A significant difference between both studied groups regarding IgG antibodies levels against Proteus mirabilis was detected (P< 0.001). No significant difference was observed between both studied groups regarding IgG antibodies levels against E. coli (P= 0.902). Significant positive correlation was found between Proteus mirabilis IgG antibodies levels and the levels of ESR and CRP in RA patients. In conclusion: Proteus mirabilis seems to have a role in RA development.

Association of adipokines with rheumatic disease activity indexes and periodontal disease in patients with early rheumatoid arthritis and their first-degree relatives.

To evaluate the adipokine levels in early rheumatoid arthritis (eRA) and first-degree relatives (FDR) of patients with RA and establish their association with rheumatic disease activity and periodontal variables. A cross-sectional study with eRA patients, FDR and a healthy population. Adipokine levels, clinical, joint radiological indexes and periodontal variables were evaluated. A descriptive, bivariate analysis was performed based on the adipokine levels by χ2 , Fisher's test and Mann-Whitney U test. A logistic regression was made for associations. High leptin levels were associated with the diagnosis of eRA (odds ratio [OR]=2.79; 95% CI 1.54-5.07). Early rheumatoid arthritis with high adiponectin levels was less likely to have Multidimensional Health Assessment Questionnaire score >3, body mass index (BMI) >25 and Routine Assessment of Patient Index Data 3 score >12 (OR=0.16; 95% CI 0.03-0.72). Early rheumatoid arthritis was more likely to present high leptin and interleukin (IL)6 levels with low adiponectin simultaneously (OR=5.03; 95% CI 1.05-24.0). High leptin levels were associated with the FDR adjusted for IgG2 Porphyromonas gingivalis, swollen joints, Pgingivalis and low IL6 (OR=2.57; 95% CI 1.14-5.95). High adipokine levels in eRA may modulate the disease activity. Having more than 1 adipokine at high serum levels is associated with increased disability, disease activity and BMI, indicating that RA is controlled by adiponectin levels in the early stages of the disease. High leptin levels, presence of Pgingivalis and swollen joints may be the factors associated with the development of RA in FDR.

PTPN22 1858 C/T polymorphism is associated with alteration of cytokine profiles as a potential pathogenic mechanism in rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is one of the most common prevalent autoimmune diseases. The 1858 C/T (rs2476601) single nucleotide polymorphism (SNP) within the PTPN22 gene has been associated with susceptibility to inflammatory based diseases in several populations. It is implicated that altered cytokine production has a potential pathogenic role in the development of RA. The aim of this work was to analyze the association of 1858 C/T PTPN22 polymorphism in RA patients with cytokine profiles. Materials and MethodsThis study was performed on 120 RA patients who were referred to the Rheumatology Research Centre, Shariati Hospital (Tehran, Iran), and 120 healthy controls. Genomic DNA was extracted and genotyped for 1858 C/T PTPN22 gene SNP using the PCR-RFLP technique. Serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ as well as Anti−CCP and RF was measured by ELISA method. ResultsResults showed that 1858 C/T PTPN22 SNP significantly (P = 0.007, OR = 2.321, 95% CI = 1.063–5.067) associated with RA. The 1858 T allele frequency was also significantly increased in RA patients in comparison to the controls (P = 0.008, OR = 3.583, 95% CI = 1.3–9.878). Our data demonstrated a significant reduction of IL-4 and IL-10 in PTPN22 1858C/T compared to 1858C/C RA patients. In addition, upregulation of IL-6, IFN-γ, and TNF-α was observed in PTPN22 1858C/T vs. 1858C/C RA patients. DiscussionOur findings implicate altered cytokine profiles as a possible pathogenic mechanism by which the 1858 T allele may contribute to the progress of RA.

Improving the feasibility of MRI in clinically suspect arthralgia for prediction of rheumatoid arthritis by omitting scanning of the feet.

ObjectivesThe use of MR-imaging is recommended for the early detection of RA. Next to the small joints of the hands, foot-joints are often involved. Therefore, imaging inflammation of the feet in addition to hands may be informative, but prolongs scan-time and leads to additional costs. We studied the value of MRI of the feet alone and complementary to MRI of the hands in patients with clinically suspect arthralgia (CSA).Methods357 consecutively included CSA patients underwent contrast-enhanced 1.5 T-MRI of hand (MCP2-5 and wrist) and foot (MTP1-5) joints at baseline. Scans were scored for synovitis, osteitis and tenosynovitis. After ⩾1 year follow-up, the development of clinically apparent inflammatory arthritis (IA) was studied. Cox regression was performed and test characteristics were evaluated. Sensitivity analyses were performed for the outcome RA-development (2010-criteria).ResultsMRI-detected tenosynovitis of the feet was associated with IA-development, independently from synovitis and osteitis hazard ratio (HR) (95%CI) 4.75 (2.38; 9.49), and independently from ACPA and CRP, HR 3.13 (1.48; 6.64). From all CSA patients, 11% had inflammation in hands and feet, 29% only in hands and 3% only in feet. In line with this finding, the addition of MRI-feet to MRI-hands did not increase the predictive accuracy; the sensitivity remained 77%, while the specificity decreased from 66% to 62%. Sensitivity analyses with RA development as outcome showed similar results.ConclusionTenosynovitis at the forefeet in CSA predicted IA and RA development. Addition of foot MRI to hand MRI did not increase the accuracy. Foot MRI can be omitted to reduce scan time and costs and increase the feasibility.

In vivo imaging of early stages of rheumatoid arthritis by \u03b15\u03b21-integrin-targeted positron emission tomography

BackgroundRheumatoid arthritis (RA) is one of the most common rheumatic diseases. Joint inflammation and pathological growth of joint cartilage cause swollen and painful joints, which severely diminishes the patients’ life quality. There is no causal treatment. Symptomatic therapies should start as early as possible to take maximal effect. Hence, diagnostic procedures capable of detecting affected joints before the onset of clinical symptoms are highly desirable. We explored the value of PET imaging of integrin subtypes αvβ3 and α5β1 for early detection of RA foci in collagen-induced arthritis (CIA) mouse models.ResultsDevelopment of RA in CIA mice was monitored by paw scoring, and αvβ3- and α5β1-integrin expression was quantified by μPET using 68Ga-Avebetrin and 68Ga-Aquibeprin. For consecutive sections of selected decalcified joints (knee, ankle), arthritic degeneration and integrin expression were assessed by MOVAT staining and β3/α5 immunohistochemistry (IHC), respectively. β3- and α5-IHC revealed elevated levels of both αvβ3- and α5β1-integrin in arthritic joints. Unlike αvβ3, α5β1 is strongly expressed in the proliferating synovial lining layer, which suggests that its presence is directly related to RA development. For mice with advanced RA (6 weeks after CIA), PET signals for α5β1-integrin were substantially stronger (> 300% of baseline) than that of αvβ3-integrin (< 200%). A longitudinal PET follow-up revealed that the manifestation of clinical symptoms of RA is preceded by upregulation of α5β1- but not of αvβ3-integrin.Conclusionα5β1-integrin PET could add a new functional imaging aspect to the portfolio of RA diagnostics because it appears to be a sensitive biomarker for early RA development. We suggest α5β1-integrin PET as a valuable tool to achieve a higher precision for early diagnosis of RA, including initial staging, monitoring of the disease course, and drug treatment, and for planning of radiosynoviorthesis (RSO).

Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk.

ObjectivesConsidering growing evidence of mucosal involvement in RA induction, this study investigated circulating free secretory component (SC) in patients with either recent-onset RA or with ACPA and musculoskeletal pain.MethodsTwo prospective cohorts were studied: TIRA-2 comprising 452 recent-onset RA patients with 3 years of clinical and radiological follow-up, and TIRx patients (n = 104) with ACPA IgG and musculoskeletal pain followed for 290 weeks (median). Blood donors and three different chronic inflammatory diseases served as controls. Free SC was analysed by sandwich ELISA.ResultsSerum levels of free SC were significantly higher in TIRA-2 patients compared with TIRx and all control groups (P < 0.01). Among TIRx patients who subsequently developed arthritis, free SC levels were higher compared with all control groups (P < 0.05) except ankylosing spondylitis (P = 0.74). In TIRA-2, patients with ACPA had higher baseline levels of free SC compared with ACPA negative patients (P < 0.001). Free SC status at baseline did not predict radiographic joint damage or disease activity over time. In TIRx, elevated free SC at baseline trendwise associated with arthritis development during follow-up (P = 0.066) but this disappeared when adjusting for confounders (P = 0.72). Cigarette smoking was associated with higher levels of free SC in both cohorts.ConclusionSerum free SC levels are increased in recent-onset RA compared with other inflammatory diseases, and associate with ACPA and smoking. Free SC is elevated before arthritis development among ACPA positive patients with musculoskeletal pain, but does not predict arthritis development. These findings support mucosal engagement in RA development.

Bariatric surgery and the incidence of rheumatoid arthritis - a Swedish Obese Subjects study.

ObjectiveThe aim of this study was to determine the effect of bariatric surgery on the incidence of RA in participants of the Swedish Obese Subjects (SOS) study.MethodsThe SOS is a longitudinal study aiming to assess the effect of bariatric surgery on mortality and obesity-related diseases. This report includes 2002 subjects with obesity who underwent bariatric surgery and 2034 matched controls; none of them had RA at baseline. Cases of incident RA were identified through the Swedish National Patient Register by searching for International Classification of Diseases codes. Both intention-to-treat analyses and per-protocol analyses are reported. In the per-protocol analysis, participants from the control group who underwent bariatric surgery later on during follow-up were censored at the time of surgery.ResultsDuring follow-up, 92 study participants developed RA. The median follow-up was 21 years (range 0–29). Bariatric surgery was neither associated with the incidence of RA in the intention-to-treat analysis [hazard ratio (HR) 0.92 (95% CI 0.59, 1.46), P = 0.74], nor in the per-protocol analysis [HR 0.86 (95% CI 0.54, 1.38), P = 0.53]. Weight change at the 2 year follow-up, expressed as the change in BMI compared with baseline, did not associate with the development of RA. Higher serum CRP levels and smoking associated with the future development of RA independent of other factors.ConclusionsWe did not detect any association between bariatric surgery and the incidence of RA in subjects affected by obesity followed up for up to 29 years.ClinicalTrials.gov(http://clinicaltrials.gov): NCT01479452.

Cytokines and MMP-9 Levels in Rheumatoid Arthritis and Osteoarthritis Patients with Persistent Parvovirus B19, HHV-6 and HHV-7 Infection

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes erosive changes and ankylosis of joints and may cause internal injuries. Osteoarthritis (OA) is a degenerative process of the articular cartilage. However, inflammatory mediators may play a pivotal role in the initiation and perpetuation of the OA process. It is necessary to continue to study possible factors that may promote the development of the disease. The goal of this study was to evaluate the frequency and activity stage of parvovirus B19 (B19V) and persistent human herpes virus (HHV)-6 and HHV-7 infection in RA and OA patients, and healthy persons, in relation to cytokine levels and presence or absence of viral infections. RA patients with active B19V infection had the highest levels of tumour necrosis factor alpha (TNF-α), which may contribute to the development of RA. In the case of OA, the TNF-α level was higher in patients with active persistent B19V infection, suggesting that B19V reactivation affects also OA. Interleukin (IL)-6, IL-10 and metalloproteinase (MMP)-9 levels were higher in RA patients with latent HHV-6/-7 infection in comparison with active HHV-6/-7 infection, whereas in OA patients levels of all studied cytokines were very variable, ranging from low to high but without significant differences. This suggests that also latent HHV-6 and -7 viral infections can promote development of RA.

The clinical aspect of overweight on rheumatoid arthritis and disease activity

Objective: To investigate the influence of obesity on disease activity in rheumatoid arthritis patients and to determine a probable connection with the acute phase response. Materials and methods: The recruited patients satisfied the criteria from the American College of Rheumatology (ACR). To evaluate the body mass index (BMI), anthropometric tests were carried out at the Rheumatology Department at Baquba Teaching Hospital, which has a consultation unit. The serum levels of anti-cyclic citrullinated peptide antibodies (anti-CCP) were measured from blood samples taken through the particle-enhanced (latex) immunonephelometry assays on the genius analyser (CO, Ltd. China) and test kits from IMTEC-CCP-Antibodies. RF screen and serological tests (latex) were carried out to determine the C-reactive protein (CRP), measure Hb and the total WBCs count, the erythrocyte sedimentation rate (ESR) was also carried out. Results: The current study findings from the sample of RA patients showed that the proportion of patients falling into the overweight classification (BMI 25-29) was 80.6% while the obese classification (BMI 30-35) was 33.33%. Among the RF and ACCP-positive cases, a marginally stronger relationship between the development of RA and the history of obesity was found. Additionally, a significant correlation between acute phase response and free mass was found in RA patients (anti-CCP p-value≤ 0.00021 ESR p≤ 0.00072 Hb p≤ 0.00054, and W.B.C p =≤ 0.000.94, CRP p≤1). Conclusion: The present study’s findings show an elevated prevalence of high body mass among the RA patients. Furthermore, a linear association existed between the fat free mass and the acute phase response.

Periodontal status correlates with anti-citrullinated protein antibodies in first-degree relatives of individuals with rheumatoid arthritis.

To evaluate periodontal status in first-degree relatives of patients with rheumatoid arthritis (FDR-RA) and detect correlation with the presence of anti-citrullinated protein antibodies (ACPAs). Rheumatologic status and periodontal status were evaluated in a nested case-control study of FDR-RA with no diagnosis of RA at enrolment. The following parameters were assessed in 34 ACPA-positive (ACPA+) and 65 ACPA-negative (ACPA-) subjects: gingival index (GI), plaque index (PI), probing depth (PD), bleeding on probing (BOP) and clinical attachment level (CAL). We compared the two groups using conditional logistic regression. In ACPA+ individuals, the mean, PD, BOP, CAL and number of sites per person with PD>4mm and BOP were significantly higher compared tothe ACPA- group. All ACPA+ subjects had periodontitis: 44.1% presenting moderate and 47.1% severe periodontitis. ACPA- subjects had mainly mild (30.8%) and moderate (27%) periodontitis, differences being significantly different for both moderate periodontitis (p=0.001) and severe periodontitis (p<0.001). In multivariable analyses, ACPA status (p=0.04) and age (p=0.002) were significantly andindependently associated with periodontal conditions. High prevalence and severity of periodontitis in FDR-RA was associated with seropositivity to ACPAs. This further strengthens the hypothesis that periodontitis may be a risk factor in the development of RA.

Quantifying circulating Th17 cells by qPCR: potential as diagnostic biomarker for rheumatoid arthritis.

The diagnosis of RA patients remains a challenge, especially in ACPA-negative disease. Novel T-cell subsets, particularly Th17 may be useful, although data on Th17 frequency using flow cytometry in RA are conflicting. We investigated whether a novel epigenetic qPCR assay for the quantification of Th17 could differentiate patients with RA from those with symptoms evolving towards an alternative diagnosis. We used a qPCR assay measuring the extent of the methylation at a key position in the IL-17 and CD4 genes. Assays were performed on whole blood from 49 healthy controls (HC) and 165 early arthritis clinic patients. Flow cytometry was further used to detect the expression of CXCR4 on Th17 cells. In 75 inflammatory arthritis patients who progressed to RA, the qPCR assays showed significantly fewer Th17 cells compared with 90 patients who did not (P<0.0001). Regression models demonstrated a high predictive value for RA development (75.8% correct prediction), and particularly for the ACPA-negative group (n = 125) where Th17 and swollen joint count (SJC) were the only predictors (73% correct prediction). The chemokine receptor CXCR4 had significantly higher expression on Th17 from early RA patients (n = 11) compared with HC (n = 15). The results of the epigenetic qPCR assay showed that low levels of Th17 cells were predictive of developing RA, particularly in the ACPA-negative patients. This could have value for insights into pathogenesis and management. The results suggest the recruitment of Th17 to the inflammatory disease site, consistent with high CXCR4 expression.

Anti-CD11b antibody treatment suppresses the disease conditions in rheumatoid arthritis (RA)-prone, FcγRIIB-deficient mice

Abstract Previously we established a RA-prone, FcγRIIB deficient mouse strain (KO1). Anti-mouse CD11b mAb (5C6) has been reported to inhibit the recruitment of CD11b+ myelomonocytic cells from the blood to the inflammatory site. The CD11b+ cells include neutrophils and monocytes, both of which are known to play important roles in the development of RA. In this study, we treated KO1 mice with 5C6 mAb to examine its effects on RA development. Four-month-old preclinical KO1 mice were treated for 6 months; with 5C6, rat IgG as a control, or none. Among the 3 groups of mice, the severity of RA and immunological abnormalities were compared. RA-related factors in the ankle joints, spleens, and peripheral blood cells were examined. The 5C6 treatment ameliorated the conditions of RA in KO1 mice, along with the decreases in inflammatory-cell infiltration and osteoclast formation. Transcriptional level analysis for the ankle joints showed that the 5C6 treatment down-regulated the expressions of RANK, RANKL, MCP-1, RANTES, TNFα, and IL-6; and up-regulated that of osteoprotegerin, the decoy receptor for RANKL. Suppression of RA was associated with the lower serum level of autoantibodies, and the decreased frequency of activated B cells. Expressions of B-cell stimulating cytokines were suppressed in the spleens and peripheral leukocytes of the 5C6-treated mice. While untreated KO1 mice spontaneously developed marked monocytosis, the frequency of monocytes was significantly downregulated in the 5C6-treated mice. It is thought that the 5C6-mediated suppression of RA is caused by the decreased numbers of inflammatory cells and monocytes per se at the joints; also secondarily by the reduced amounts of B-cell stimulating cytokines, leading less autoantibodies.

Prevotella copri in individuals at risk for rheumatoid arthritis

ObjectivesRheumatoid arthritis (RA) has been associated with a relative expansion of faecal Prevotellaceae. To determine the microbiome composition and prevalence of Prevotella spp. in a group of individuals at increased...