Rheumatism Classification Criteria For Rheumatoid Arthritis Research Articles

Cachexia Prevalence in a Population of Moroccan Women with Rheumatoid Arthritis.

To assess body composition in women with rheumatoid arthritis (RA) compared to healthy controls, to calculate the prevalence of rheumatoid Cachexia (RC), and to identify the associated factors. We conducted a case-control study on 112 female patients with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA; and 224 age-matched healthy women. Body composition (BC) and bone mineral density (BMD) scans were obtained using Dual-energy X-ray absorptiometry (DXA). RC was defined by a fat-free mass index (FFMI) below the 10th percentile and a fat mass index (FMI) above the 25th percentile compared with the control group. We conducted a comparison between RA patients and healthy controls then a multiple regression analysis was conducted where the dependant variable is the presence of RC. RC prevalence was 42.85% while the mean body mass index (BMI) was the same in both groups. RA patients had a higher FM and lower FFM comparing to healthy controls. In our population, 78.60% of patients were on methotrexate and 12.50% on anti TNF therapy. Comparison between patients with and without RC showed that patients with RC have a higher proportion of erosive arthritis and of active disease. Regression logistic analysis showed that RC was significantly associated to erosive arthritis and active disease (OR at 33.31 (8.42-131.70) and 8.98 (1.64-49.20) respectively), independently of age, erythrocyte sedimentation rate, C-reactive protein, disease duration, steroid cumulative dose and biologic Disease-Modifying Anti-Rheumatic Drugs(bDMARDs) use. Our study showed that almost half of our RA patients have RC, even with a high BMI.

China rheumatoid arthritis registry of patients with Chinese medicine (CERTAIN): Rationale, design, and baseline characteristics of the first 11,764 enrollees

BackgroundChinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PurposeThe main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. Study designThe CERTAIN is a prospective, multicenter, observational disease registry. MethodsAdult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. ResultsIn the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. ConclusionsThe CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. RegistrationThe study was registered at ClinicalTrials.gov (NCT05219214).

Adherence to the dietary approaches to stop hypertension dietary pattern and rheumatoid arthritis in Iranian adults.

To examine the hypothesis that rheumatoid arthritis (RA) patients are less likely than healthy individuals to adhere to the dietary approaches to stop hypertension (DASH) dietary pattern. A multi-centre cross-sectional study involving a total of 300 eligible Iranian adults (aged >19 years; 93·0 % female) recruited during 2019-2020. Participants' actual dietary intakes were measured via self-administered 3-d dietary records. The DASH score was computed based on the energy-adjusted intakes of eight major dietary components usually emphasised (i.e. fruits, vegetables, nuts and legumes, low-fat dairy products and whole grains) or minimised (i.e. sweets, red or processed meats and sodium) in the DASH diet. The higher the DASH score of subjects, the greater their adherence to the DASH pattern. The outpatient clinics of major general hospitals in Shiraz, Iran. 100 incident cases with definite RA according to the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA and 200 apparently healthy controls frequency-matched by gender and age. After adjusting for several potential covariates in the binary logistic regression analysis, RA cases were less likely than controls to have high adherence to the DASH pattern (OR = 0·08; 95 % CI 0·03, 0·20; P = 0·001). Our findings in a sample of Iranian adults revealed that RA patients are less likely than healthy individuals to adhere to the DASH dietary pattern. However, the potential causal association of greater adherence to the DASH pattern and lower risk of RA needs to be confirmed by prospective studies of high methodological quality.

Clinical Profile and Comorbidities Associated with Rheumatoid Arthritis Patients in Sudair, Saudi Arabia.

Background:Rheumatoid arthritis (RA) is a chronic, debilitating condition that has a significant effect on the lives of patients, their families, and society at large.Aims:The aim is to determine the clinical profile and any comorbidities associated with RA patients in the Sudair region of Saudi Arabia.Subjects and Methods:Sixty patients were included in this cross-sectional observational study, both newly or already diagnosed with RA, fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA. They were followed up in the rheumatology clinic in King Khalid Majmaah Hospital in the Majmaah province from January 2017 to December 2020.Results:The subjects' mean age was 47.87 ± 11.55 years, 52 female and 8 male (female-to-male ratio 6.5:1). About 23.3% of patients with RA had positive family history. The main comorbidities and associated diseases were hypertension (18.3%) and hypothyroidism (15%). The most frequently involved joints were the wrist, metacarpophalangeal, proximal interphalangeal, elbow, and knee joints. Subjects were positive in 66.7% for rheumatoid factor and 78.3% for anti-cyclic citrullinated peptide. Both markers were positive in 60% of the patients.Conclusion:Approximately one-quarter of the studied group had a family history of RA. Hypertension followed by hypothyroidism was the most common comorbidities reported in our study.

First-in-human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti-CD40 monoclonal antibody.

Iscalimab is a fully human, CD40 pathway blocking, nondepleting monoclonal antibody being developed as an immunosuppressive agent. We describe a first-in-human, randomized, double-blind, placebo-controlled study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of iscalimab in healthy subjects and rheumatoid arthritis patients. Healthy subjects (n=56) received single doses of intravenous iscalimab (0.03, 0.1, 0.3, 1, or 3mg/kg), or subcutaneous iscalimab (3mg/kg), or placebo. Rheumatoid arthritis patients (n=20) received single doses of intravenous iscalimab (10 or 30mg/kg) or placebo. Iscalimab exhibited target-mediated drug disposition resulting in dose-dependent and nonlinear pharmacokinetics. Complete (≥90%) CD40 receptor occupancy on whole blood B cells was observed at plasma concentrations >0.3-0.4µg/mL. In subjects receiving 3mg/kg iscalimab, antibody responses to keyhole limpet hemocyanin were transiently suppressed. CD40 occupancy by iscalimab prevented ex vivo human rCD154-induced expression of CD69 on B cells in whole blood. All doses were generally safe and well tolerated, with no clinically relevant changes in any safety parameters, including no evidence of thromboembolic events. Iscalimab appears to be a promising blocker of the CD40-CD154 costimulatory pathway with potential use in transplantation and other autoimmune diseases.

Diastolic dysfunction in patients with rheumatoid arthritis

ObjectiveThe aim of this study was to evaluate left ventricular diastolic function parameters as an early predictor of cardiac involvement in patients with rheumatoid arthritis (RA) without any evidence of hypertension, diabetes mellitus, rheumatic fever or underlying cardiac disease, detected by Doppler echocardiography and to correlate diastolic function in RA patients with different RA disease characteristics.Patients and methodsSeventy-five RA patients were diagnosed according to the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA and another 38 age-matched and sex-matched healthy participants were included. All patients and the control groups were submitted to M-mode, two-dimensional, Doppler (continuous and pulsed wave) echocardiography. Diastolic dysfunction was defined as when transmitral flow E/A ratio is less than one.ResultsLeft ventricular diastolic dysfunction was found in 28 (37.3%) of 75 RA patients and four (10.5%) of 38 controls with a P value of less than 0.05. In the patients’ group, a statistically significant correlation was found between diastolic dysfunction and duration of the disease (P<0.05), and disease activity was assessed by 28 Joint Disease Activity Score (P<0.05).ConclusionAmong those without a history of cardiac disease, patients with RA have a higher prevalence of diastolic dysfunction than those without RA. Diastolic dysfunction in RA was associated with disease duration and disease activity. Thus, early identification of diastolic dysfunction in asymptomatic RA patients by the use of echocardiography may provide an opportunity to manage the underlying etiology to prevent progression to diastolic heart failure.

The value of joint ultrasonography in predicting arthritis in seropositive patients with arthralgia: a prospective cohort study

BackgroundThe value of joint ultrasonography (US) in the prediction of clinical arthritis in individuals at risk of developing rheumatoid arthritis (RA) is still a point of debate, due to varying scanning protocols and different populations. We investigated whether US abnormalities assessed with a standard joint protocol can predict development of arthritis in seropositive patients with arthralgia.MethodsAnti-citrullinated protein antibodies and/or rheumatoid factor positive patients with arthralgia, but without clinical arthritis were included. US was performed at baseline in 16 joints: bilateral metacarpophalangeal 2–3, proximal interphalangeal 2–3, wrist and metatarsophalangeal (MTP) joints 2–3 and 5. Images were scored semi-quantitatively for synovial thickening and for positive signs on power Doppler (PD). Association between US abnormalities and arthritis development at the joint and at the patient level was evaluated. Also, we investigated the added value of US over clinical parameters.ResultsOut of 163 patients who underwent US examination, 51 (31%) developed clinical arthritis after a median follow-up time of 12 (interquartile range 5–24) months, of which 44 (86%) satisfied the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA. US revealed synovial thickening and PD in at least one joint in 49 patients (30%) and 7 patients (4%), respectively. Synovial thickening was associated with both development and timing of clinical arthritis in any joint (patient level) when MTP joints were excluded from the US assessment (odds ratio 6.6, confidence interval (CI) 1.9–22), and hazard ratio 3.4, CI 1.6–6.8, respectively, with a mean time to arthritis of 23 versus 45 months when synovial thickening was present versus not present). There was no association between US and arthritis development at the joint level. Predictive capacity was highest in the groups with an intermediate and high risk of developing arthritis based on a prediction rule with clinical parameters.ConclusionsSynovial thickening on US predicted clinical arthritis development at the patient level in seropositive patients with arthralgia when MTPs were excluded from the US assessment. Positive PD signs were infrequently seen in these at-risk individuals and was not predictive. In patients at intermediate risk of RA, US may help to identify those at higher risk of developing arthritis.

The impacts of state and trait anxiety as moderated by perceived social support among Nigerian patients with rheumatoid arthritis.

ObjectivesTo assess the levels of state and trait anxiety and determine their relationships with perceived social support among Nigerian patients with rheumatoid arthritis (RA).Material and methodsA cross-sectional study of 50 patients satisfying the 2010 American College of Rheumatology/European League against Rheumatism Classification Criteria for RA was conducted. Anxiety was assessed using the Spielberger State-Trait Anxiety Inventory (STAI), perceived social support by the Interpersonal Support Evaluation List (ISEL), health-related quality of life (HRQoL) by the Medical Outcome Study 36-Item Short Form Health Survey (SF-36) and disability by the Health Assessment Questionnaire-Disability Index (HAQ-DI).ResultsThe mean state anxiety (STAI-S), trait anxiety (STAI-T) and ISEL scores among the patients were 35.2 ±10.2, 36.7 ±8.8 and 87.2 ±21.2 respectively. Pathological degrees of state and trait anxiety were found among 7 (14%) and 5 (10.4%) patients respectively. There was a negative correlation between the STAI-T score and the ISEL score (r = –0.362, p = 0.011). However, the correlation between STAI-S and ISEL was not statistically significant (r = –0.193, p = 0.179). A moderate-to-high correlation was found between each of STAI-S and STAI-T and all subscales and component summaries of the SF-36. ISEL score correlated significantly with role emotional (r = 0.377, p = 0.008), mental health (r = 0.482, p ≤ 0.001) and bodily pain (r = 0.320, p = 0.025) domains and the mental component summary (r = 0.380, p = 0.007) of SF-36. HAQ-DI correlated strongly with both STAI-S (r = 0.735, p ≤ 0.001) and STAI-T (r = 0.575, p ≤ 0.001) but not with ISEL.ConclusionsState and trait anxiety correlate negatively with all aspects of HRQoL and disability, and there is a notable relationship between perceived social support and trait anxiety as well as the mental aspect of HRQoL.

Ultrasonographic findings of the shoulders in Egyptian patients with rheumatoid arthritis

ObjectiveThis study aimed to highlight the diagnostic value of musculoskeletal ultrasonography (US) in the evaluation of inflammatory changes in the shoulders of rheumatoid arthritis (RA) patients and to correlate those findings with the clinical, laboratory, and radiological parameters of the disease activity.Patients and methodsThis study included 40 RA patients diagnosed according to the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA. In addition, 20 age-matched and sex-matched healthy individuals were included. US assessment was performed bilaterally in RA patient’s shoulder and unilaterally in controls. All US examinations were carried out using LOGIQ P6 PRO machine equipped with 6–8 MHz broadband multifrequency linear transducer.ResultUS on shoulders detected that 21 (52.5%) RA patients studied had erosions, 18 (45%) RA patients had synovitis, 21 (52.5%) RA patients had tenosynovitis, seven (17.5%) RA patients had bursitis, and 18 (45%) RA patients had rotator cuff tendinopathy. There was a significant relation between US-detected erosion in RA patients and disease duration (P = 0.037) and rheumatoid factor (RF) level (P = 0.02), whereas there was no significant relation between US-detected erosion in RA patients and shoulder pain (P = 0.185), Disease activity score 28 (DAS28) (P = 0.163), erythrocyte sedimentation rate (P = 0.519), and C-reactive protein levels (P = 0.561). There was a significant relation between US-detected tenosynovitis in RA patients and shoulder pain (P = 0.025). There was no significant relation between US-detected bursitis in RA patients and disease duration (P = 0.970), shoulder pain (P = 0.907), DAS28 (P = 0.471), erythrocyte sedimentation rate (P = 0.220), and RF levels (P = 0.755), whereas there was a significant relation between US-detected bursitis in RA patients and C-reactive protein (P = 0.036).ConclusionUS became a problem-solving approach and the tool of choice for cases with shoulder problem, and can provide an accurate answer to many clinical questions and give an accurate diagnosis of different pathological abnormalities encountered.

PREVALENCE OF DYSLIPIDEMIA AND ITS ASSOCIATION WITH DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS IN SULAIMANI GOVERNORATE

Objectives: Rheumatoid arthritis is a systemic inflammatory disease characterized by chronic and erosive polyarthritis it is the most common inflammatory arthritis, affecting from 0.5-1% of the general population. Dyslipidemia is a quite important problem in Rheumatoid arthritis (RA) patient, which causes morbidity and mortality. Objectives are to measure prevalence of dyslipidemia in patients with Rheumatoid Arthritis compared with healthy control peoples and to find out correlations between dyslipidemia and disease activity in patients with Rheumatoid Arthritis. Methods: A total of one hundred patients with RA (80 female and 20 male) were included in the study, they were attending consultation clinic and division of rheumatology in the General Medical Teaching Hospital in Slemani city from (October 2015 to September 2016) who fulfilling the 2010 American College of Rheumatology/European league against Rheumatism classification criteria for RA and one hundred healthy age and sex-matched controls. Fasting lipid profiles of cases and control were estimated after an overnight fast of 12 hours. Results: RA patients showed a higher prevalence of associated dyslipidemia (48%) in comparison to control (4%) p- value less than 0.001. Results showed a significant reduction in serum high density lipoproteins (HDL) p-value less than 0.001, with significant elevation of serum total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein p-value 0.001, 0.007, 0.01and 0.5 respectively in comparison to controls. There is a significant association between dyslipidemia and high DAS 28 score (p=0.02). Conclusion: There is a significant association between high ESR of RA patients and dyslipidemia (p=0.001). A significant association was observed between high CRP level and RA patients with no dyslipidemia (p<0.001). Dyslipidemia are frequent among the patients with rheumatoid arthritis and highly associated with active RA. Serum HDL significantly reduced while other parameters of lipid profiles significantly increased in comparisons to control. Peer Review History: Article received on- 19 November, Revised on- 26 December, Accepted on- 30 December, Available online 15 January 2017 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Ahmad Abdelsattar El-Ebiary, Tanta University Hospitals, Tanta, Egypt, a.ebiary@med.tanta.edu.eg Dr. Areen Alshweiat, University of Szeged, Hungary, areen.alshweiat@hu.edu.jo Similar Articles: SEROPREVALENCE OF ANTI-MANNOSE BINDING LECTIN AUTOANTIBODIES IN PATIENTS WITH RHEUMATOID ARTHRITIS IN SANA'A CITY- YEMEN

Vitamin D, inflammatory markers, steroid use and systemic factors: which is the culprit in rheumatoid arthritis associated osteoporosis?

Aim . To explore the risk factors for osteoporosis in Rheumatoid Arthritis (RA) patients. Methods . A cross-sectional study was conducted on 93 patients meeting the American College of Rheumatology – European League Against Rheumatism classification criteria for RA 2010(ACR-EULAR). Serum 25-OH vitamin D (25(OH) D levels was measured. In addition, the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), rheumatoid factor (RhF), anticyclic - citrullinated protein/peptide antibodies (Anti-CCP) were assessed. Dual-energy X-ray absorptiometry (DEXA) was also used to measure the bone mineral density BMD of the left femur at the time of recruitment. Results . The RA cohort was predominantly female (88.2%). The average age of the participants was 46.5±15.2 years. Osteoporosis was present in 25 (26.9%). Osteoporotic cases were significantly older (p <0.001) , female (p = 0.032) and had significantly more frequencies of diabetes (p = 0.022) and hypertension (p = 0.018) and had significantly lower calcium (p = 0.038 ). Logistic regression model for factors affecting osteoporosis showed that Steroids intake, increasing age and decreasing serum calcium were factors increasing the likelihood of having osteoporosis. Vitamin D did not show any relation with osteoporosis. Serum inflammatory markers like ESR, CRP, R.F and anti- CCP were higher in osteoporotic group but not significant. Conclusions . The results of this analysis indicated that systemic factors like age and intake of steroids are culprit factors in rheumatoid arthritis associated osteoporosis.

Effect of Methotrexate Use and Erythrocyte Methotrexate Polyglutamate on Glycosylated Hemoglobin in Rheumatoid Arthritis

To investigate whether methotrexate (MTX) use, as compared to other therapies, and erythrocyte methotrexate polyglutamate (MTXGlu) concentrations are associated with changes in glycosylated hemoglobin (HbA1c ) levels in rheumatoid arthritis (RA) patients. The derivation cohort consisted of patients selected from the Treatment in the Rotterdam Early Arthritis Cohort who fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA. Patients were randomized to 6 treatment arms: triple disease-modifying antirheumatic drug (DMARD) therapy (consisting of MTX, sulfasalazine, and hydroxychloroquine [HCQ]) + intramuscular (IM) glucocorticoids, triple DMARD therapy + oral glucocorticoids, MTX + oral glucocorticoid therapy, MTX therapy, oral glucocorticoid therapy, and HCQ therapy. HbA1c levels were determined at baseline and at 3 months. Concentrations of erythrocyte MTXGlu1-5 were measured after 3 months of treatment. Within treatment arms, changes in the level of HbA1c were compared by paired t-test. Associations of MTXGlu concentrations with changes in the level of HbA1c were tested using multiple linear regression analysis, adjusted for age, sex, body mass index, and comedication. Significant associations were validated using data on RA patients taking MTX who were enrolled in the Methotrexate in Rotterdam cohort. In the derivation cohort, the mean change in HbA1c level after 3 months of treatment was -1.9 mmoles/mole (-0.18%) (P = 0.001). Levels of HbA1c decreased in 4 of the individual treatment groups, as follows: for the triple DMARD therapy + IM glucocorticoids treatment arm, -5.5 mmoles/mole (-0.50%) (P < 0.001), for the triple DMARD therapy + oral glucocorticoids treatment arm, -3.7 mmoles/mole (-0.34%) (P < 0.001), for the MTX treatment arm, -0.8 mmoles/mole (-0.08%) (P = 0.018), and for the HCQ treatment arm, -2.0 mmoles/mole (-0.19%) (P = 0.175). Increased levels of MTXGlu2 (β = -0.20, P = 0.005), MTXGlu3 (β = -0.31, P < 0.001), MTXGlu4 (β = -0.33, P < 0.001) after treatment, MTXGlu5 (β = -0.39, P < 0.001), and total MTXGlu (β = -0.29, P < 0.001) were associated with decreased levels of HBA1c . In the validation cohort, levels of HbA1c were decreased by 2.6 mmoles/mole (0.23%) (P < 0.001) after treatment, and MTXGlu3 was associated with decreased levels of HbA1c (β = -0.26, P = 0.018). MTX use and higher concentrations of erythrocyte MTXGlu are associated with decreased levels of HbA1c in RA patients. Triple DMARD therapy and HCQ treatment resulted in reduced HbA1c levels, and glucocorticoid treatment resulted in increased levels of HbA1c .

Serum vitamin D level and disease activity in patients with recent onset rheumatoid arthritis

Rheumatoid Arthritis (RA) is one of the most prevalent autoimmune diseases. Due to the significance of the relationship between serum vitamin D levels and autoimmune diseases, this study aimed to determine the relationship between serum vitamin D level and the severity of disease activity in patients with newly diagnosed RA. This cross-sectional study was conducted on 66 patients meeting the American College of Rheumatology - European League Against Rheumatism classification criteria for RA. It was performed in 2012 using simple sampling. The disease activity was measured based on Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) and serum 25-OH vitamin D (25(OH)D) levels using the chemiluminescent immunoassay method. In addition, the levels of ESR and C-reactive protein (CRP), the duration of morning stiffness, and the number of joints with tenderness and swollen were calculated as well. The data were analyzed using the Pearson correlation coefficient. In this study, 10 patients were male (15.2%) and 56 were female (84.8%). The average age of the participants was 45.2 ± 15.3years. The average level of 25(OH)D in the patients' serum was 30.5±28.9ng/mL and the mean DAS28-ESR was 5.6±1.1. The correlation coefficient showed that there was an inverse relationship between 25(OH)D and DAS28-ESR, the number of tender and swollen joints, global patient assessment and duration of morning stiffness (P<0.01). However, the average 25(OH)D level was not related to ESR (P=0.779) and CRP (P=0.269). The results of this analysis indicated that patients with more active RA have a lower serum vitamin D level.

Very high levels of anti–citrullinated protein antibodies are associated with HLA–DRB1*15 non–shared epitope allele in patients with rheumatoid arthritis

Production of anti-citrullinated protein antibodies (ACPAs) is an important biomarker for rheumatoid arthritis (RA). We undertook this study to determine whether genetic factors (HLA-DRB1 alleles) are associated with extreme ACPA levels in individuals with ACPA-positive RA, and to ascertain whether there are any phenotypic characteristics associated with these subgroups of RA. HLA-DRB1 allelic groups were genotyped in 1,073 ACPA-positive RA patients from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. We found that 283 patients (26.4%) had high ACPA levels (defined as >1,500 units/ml using the Euro-Diagnostica anti-CCP2 test), while the rest of the patients had moderate ACPA levels and served as the comparison group. A replication group consisted of 235 RA patients. No significant differences in baseline disease activity were observed between patients with high and those with moderate ACPA levels. However, the HLA-DRB1*15 allele was associated with high ACPA levels (P=0.0002). A similar trend was detected in HLA-DRB1*15-positive patients in the replication cohort, with meta-analysis of the discovery and replication cohorts demonstrating an overall effect of HLA-DRB1*15 on development of high ACPA levels in both the discovery and replication cohorts (P<0.0001 by Mantel-Haenszel test with a fixed-effects model). Our data indicate that HLA-DRB1*15 may promote the production of high ACPA levels. Due to the high value of ACPA level scores in the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA, the presence of HLA-DRB1*15 may, at least in part, contribute to fulfilling the criteria for RA. This illustrates the complex nature of the genetic regulation of ACPA levels. Additional mechanistic studies of the regulation of ACPAs and ACPA-positive RA are pending.

Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis

Objective: The methionine sulfoxide reductase A (MSRA) gene is related to oxidative stress that has been involved in the susceptibility to rheumatoid arthritis (RA) in genome-wide pathway analysis and replication studies. The aim of the present study was to determine whether the MSRA gene is implicated in susceptibility to cardiovascular (CV) disease in RA patients.Methods: A total of 1302 patients fulfilling the 1987 American College of Rheumatism classification criteria for RA were genotyped for the MSRA rs10903323 (G/A) polymorphism. Two hundred and thirty-three (17.9%) patients experienced CV events. Human leucocyte antigen (HLA)-DRB1 genotyping was performed using molecular-based methods. Multiple logistic regression models were constructed with adjustments for gender, age at RA diagnosis, follow-up, rheumatoid shared epitope, and traditional CV risk as potential confounders.Results: There were no statistically significant differences in the allele or genotype frequencies for the MSRA rs10903323 polymorphism between RA patients who experienced CV events and those who did not. However, an adjusted logistic regression model disclosed that the minor allele G yielded a marginally significant increased risk of CV events in this series of patients with RA [p = 0.05, odds ratio (OR) 1.68, 95% confidence interval (CI) 1.00–2.85]. When the logistic regression model was adjusted for anti-cyclic citrullinated peptide (anti-CCP) antibody status instead of for shared epitope, an increased risk of having ischaemic heart disease was found in patients carrying the minor allele G (p = 0.04, OR 2.00, 95% CI 1.03–3.88).Conclusion: The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to develop CV events, in particular ischaemic heart disease, observed in RA patients.