Rheumatoid Factor Status Research Articles

Brief Report: Association of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan-European Registry Analysis.

To investigate the role of rheumatoid factor (RF) status and anti-citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA). We conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden], ATTRA [Czech Republic], BIOBADASER [Spain], DANBIO [Denmark], GISEA [Italy], NOR-DMARD [Norway], ORA [France], Reuma.pt [Portugal], and SCQM-RA [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated. We identified 2,942 patients with available data on RA-associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease- and treatment-related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason (HR 0.79 [95% CI 0.69-0.90], P < 0.001 and HR 0.78 [95% CI 0.68-0.90], P < 0.001, respectively), compared to RF-negative and ACPA-negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61-0.84) and 0.74 (95% CI 0.62-0.88), respectively (both P < 0.001). Our results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy.

Prevalence of Periodontitis in Patients with Established Rheumatoid Arthritis: A Swedish Population Based Case-Control Study.

IntroductionThe possible hypothesis of a link between periodontitis and rheumatoid arthritis (RA), specifically anti-citrullinated protein antibody (ACPA) positive RA, prompted us to investigate the prevalence of periodontitis in the Swedish Epidemiological Investigation of RA (EIRA), a well-characterised population-based RA case-control cohort.MethodsPeriodontal status of 2,740 RA cases and 3,942 matched controls was retrieved through linking EIRA with the National Dental Health Registry (DHR), where dental diagnostic- and treatment codes on the adult Swedish population have been registered. Dental records from 100 cases and controls were reviewed to validate the periodontal diagnostic codes in DHR.ResultsThe reviewed dental records confirmed 90% of the periodontitis diagnoses in DHR among RA cases, and 88% among controls. We found the positive predictive value of periodontitis diagnoses in the DHR to be 89% (95% CI 78 to 95%) with a sensitivity of 77% (95% CI: 65 to 86%). In total, 86% of EIRA participants were identified in DHR. The risk for periodontitis increased by age and current smoking status in both cases as well as controls. No significant differences in prevalence of periodontal disease in terms of gingivitis, periodontitis, peri-implantitis or increased risk for periodontitis or peri-implantitis were observed between RA cases and controls. In addition, there was no difference on the basis of seropositivity, ACPA or rheumatoid factor (RF), among patients with RA.ConclusionsOur data verify that smoking and ageing are risk factors for periodontitis, both in RA and controls. We found no evidence of an increased prevalence of periodontitis in patients with established RA compared to healthy controls, and no differences based on ACPA or RF status among RA subjects.

The association between anti-carbamylated protein (anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis: a study exploring replication and the added value to ACPA and rheumatoid factor

ObjectiveAnti-carbamylated protein (anti-CarP) antibodies are reported to associate with more radiographic progression within the total rheumatoid arthritis (RA) population and anti-citrullinated peptide antibody (ACPA)-negative subgroup. We explored the association of...

Serum adiponectin and its impact on disease activity and radiographic joint damage in early rheumatoid arthritis – A cross-sectional study

ObjectiveTo study the level of serum adiponectin in steroid and DMARD naïve early rheumatoid arthritis patients and its correlation with disease activity and radiographic damage. Materials and methodsForty-three patients fulfilling ACR 2010 criteria for rheumatoid arthritis, with disease duration less than 2 years and 25 age, sex and BMI matched controls were recruited for the study between July 2012 to January 2013. Demographic data, tender joint count, swollen joint count, erythrocyte sedimentation rate, and rheumatoid factor status were recorded. Radiographs of hands and feet were obtained. BMI, DAS28-ESR and HAQ-DI were calculated. Serum concentration of adiponectin was measured by ELISA. ResultsAmong 43 early rheumatoid patients (38 females), 18 had erosive disease. There were 25 controls (21 females). Median serum adiponectin levels (14μg/ml), range (8.5–19) were significantly higher in early RA patients compared to controls (10.2μg/ml), range (7.9–13.5) (p=0.02). No difference in the adiponectin levels between erosive and nonerosive disease was noted. No correlation to duration of disease, BMI, waist hip ratio and disease activity was noted. ConclusionIn this study, while exploring the levels of adiponectin in a cohort of early RA, we observed increased serum adiponectin concentration in steroid and DMARD naïve early rheumatoid arthritis patients.

FCRL3 gene polymorphisms as risk factors for rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. As a member of FCRLs clusters, Fc receptor-like 3 (FCRL3) has been recognized as a neoteric autoimmune activation factor for RA. The aim of our study is to evaluate the correlation between four single-nucleotide polymorphisms (SNPs) on FCRL3 and RA risk in a Chinese Han population. Material and methodsThe hospital-based case-control study included 630 RA patients together with 696 healthy individuals as the control group and all subjects are Chinese ancestry. Four tagging single-nucleotide polymorphisms (tag-SNPs) on FCRL3 were selected and genotyped by TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were employed to evaluate the correlations between FCRL3 polymorphisms and RA. A systematic meta-analysis was also carried out based on the present study and previously published studies to further examine the association between FCRL3 variations and RA risk. ResultsSignificant association was found between −169T/C SNP and RA risk (CC vs. TT, OR=1.62, 95% CI=1.18–2.22; TC/CC vs. TT, OR=1.47, 95% CI=1.18–1.84; C vs. T, OR=1.32, 95% CI=1.12–1.54). Apart from that, mutations of −169T/C was significantly correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positive status. The meta-analysis also suggested that −169T/C mutation might have positive correlation with risk of RA in the overall population, particularly for Asian. Stratified analysis based on clinical characteristics of RF and ACPA also provided evidence that −169T/C polymorphisms could alter phenotypes of RA. ConclusionThe FCRL3 −169T/C variant was significantly linked with an increased RA risk in the Chinese Han population. Moreover, this meta-analysis also provides notion that −169T/C variant could act as a susceptible factor for RA. However, further investigations about the functional impacts of this polymorphism are essential to confirm the above conclusions.

Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose–response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial

ObjectivesTo evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients...

High serum cholesterol predicts rheumatoid arthritis in women, but not in men: a prospective study.

IntroductionEnvironmental exposures, including smoking, hormone-related factors, and metabolic factors, have been implicated in the etiology of rheumatoid arthritis (RA). A previous study has indicated that blood lipid levels may influence the development of RA. The objective of this study was to investigate the impact of serum total cholesterol and triglycerides on the risk of RA in a prospective study.MethodsAmong participants in a large population-based health survey (n = 33,346), individuals who subsequently developed RA were identified by linkage to four different registers and a structured review of the medical records. In a nested case-control study, with controls, matched for age, sex, and year of inclusion, from the health survey database, the relation between serum lipids (levels of total cholesterol and triglycerides) and future RA development was examined.ResultsIn total, 290 individuals (151 men and 139 women) whose RA was diagnosed a median of 12 years (range of 1–28) after inclusion in the health survey were compared with 1160 controls. Women with a diagnosis of RA during the follow-up had higher total cholesterol levels at baseline compared with controls: odds ratio (OR) 1.54 per standard deviation; 95 % confidence interval (CI) 1.22–1.94. This association remained statistically significant in multivariate models adjusted for smoking and a history of early menopause and in analyses stratified by rheumatoid factor status and time to RA diagnosis. Total cholesterol had no significant impact on the risk of RA in men (OR 1.03; 95 % CI 0.83–1.26). Triglycerides did not predict RA in men or women.ConclusionsA high total cholesterol was a risk factor for RA in women but not in men. This suggests that sex-specific exposures modify the impact of lipids on the risk of RA. Hormone-related metabolic pathways may contribute to RA development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0804-1) contains supplementary material, which is available to authorized users.

Does combined clinical and ultrasound assessment allow selection of individuals with rheumatoid arthritis for sustained reduction of anti-tumor necrosis factor therapy?

To investigate whether a strategy combining clinical and ultrasound (US) assessment can select individuals with rheumatoid arthritis (RA) for sustained dose reduction of anti-tumor necrosis factor (anti-TNF) therapies. As part of a real-world approach, patients with RA receiving anti-TNF therapies were reviewed in a dedicated biologic therapy clinic. Patients not taking oral corticosteroids with both Disease Activity Score in 28 joints (DAS28) remission (≤2.6) and absent synovitis on power Doppler US (PDUS 0) for >6 months were invited to reduce their anti-TNF therapy dose by one-third. Between January 2012 and February 2014, a total of 70 patients underwent anti-TNF dose reduction. Combined DAS28 and PDUS remission was maintained by 96% of patients at 3 months followup, 63% at 6 months, 37% at 9 months, and 34% at 18 months followup. However, 88% of patients maintained at least low disease activity (LDA) with DAS28 <3.2 and PDUS ≤1 at 6 months. The addition of PDUS identified 8 patients (25% of those that flared) in DAS28 remission, with subclinically active disease. Those who maintained dose reduction were more likely to be rheumatoid factor (RF) negative (46% versus 17%; P = 0.03) and have lower DAS28 scores at biologic therapy initiation (5.58 versus 5.96; P = 0.038). Combined clinical and US assessment identifies individuals in remission who may be suitable for anti-TNF dose reduction and enhances safe monitoring for subclinical disease flares. Despite longstanding severe RA, a subset of our cohort sustained prolonged DAS28 and PDUS remission. LDA at biologic therapy initiation and RF status appeared predictive of sustained remission.

Associations of rheumatoid factor and anti-citrullinated peptide antibody with disease progression and treatment outcomes in patients with rheumatoid arthritis.

The objective of this study was to investigate the association of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) status with disease progression and treatment outcomes in patients with rheumatoid arthritis (RA). A total of 276 adult patients who fulfilled the American College of Rheumatology 1987 classification criteria for RA were recruited from the Rheumatology clinic, Siriraj Hospital, from January 2011 to December 2012. Demographic, clinical, and laboratory data were collected at baseline and every 3months up to 1year of follow-up. RF and ACPA were measured at baseline. Radiography of the hands and feet was performed at baseline and 1year. Patients with RF+/ACPA+ had significantly more severe disease activity and impaired functional status than those who had RF-/ACPA-. Although they received more aggressive treatment with methotrexate and combination of non-biologic, disease-modifying antirheumatic drug than other groups, fewer patients in this group achieved remission at 1 year of follow-up, especially when compared to RF-/ACPA- group (12 vs. 18%). For radiographic erosion, patients with the presence of either RF or ACPA had a higher proportion of hand erosion than seronegative patients at baseline (77, 73, 83, and 32%, p<0.001 for RF+/ACPA+, RF+/ACPA-, RF-/ACPA+, and RF-/ACPA-, respectively). After 1year of follow-up, patients who developed new erosion at the hands were more prevalent in RF+/ACPA+ (32%) and RF+/ACPA- (33%) groups. However, "newly developed" feet erosion was most common in RF+/ACPA- group (40%) than in other groups. Patients with positive either RF or ACPA or both have more severe and aggressive disease that requires intensive treatment to improve outcomes.

Human leukocyte antigen-G polymorphism influences the age of onset and autoantibody status in rheumatoid arthritis.

The study was conducted to investigate the frequency of three gene polymorphisms in the 3'-untranslated region (3'-UTR) of human leucocyte antigen-G (HLA-G) gene in south Indian patients with rheumatoid arthritis (RA) and analyze their influence on disease susceptibility, phenotype and treatment response. HLA-G 14 bp insertion (Ins)/deletion (del) (rs66554220), HLA-G +3142G>C (rs1063320) and +3187A>G (rs9380142) polymorphism was analyzed in 221 RA patients and 200 healthy controls. Frequency of HLA-G genotypes or alleles did not differ between patients and controls. Analysis based on rheumatoid factor (RF) status revealed that the frequency of allele 'A' (rs9380142) was significantly higher in RF-positive than in RF-negative patients [84% vs 74%, Yates-corrected P value (Pc) = 0.04, odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.0-3.2]. A similar difference was maintained in RF-positive female patients than their RF-negative counterparts (83% vs 71%, Pc = 0.02, OR = 1.9, 95% CI = 1.0 to 3.4) and between RF-positive and RF-negative young onset RA (YORA) patients (84% vs 73%, Pc = 0.03, OR = 1.9, 95% CI = 1.0-3.2), suggesting that rs9380142 polymorphism influenced RF status. The 14 bp Ins allele of rs66554220 was significantly more prevalent in RF-positive YORA than in RF-positive late onset RA (LORA) patients (51% vs 25%, P = 0.03, OR = 3.1, 95% CI = 1.1-9.8). Frequency of the four major haplotypes [InsGA (48%), DelGA (22%), DelCG (18%), DelCA (9.7%)] observed did not differ between cases and controls. HLA-G does not appear to be a risk factor for development of RA in south Indian Tamils but may act as a genetic modifier of clinical phenotype in terms of autoantibody production, gender preference and age at disease onset.

Characterization of cumulative joint damage patterns in patients with rheumatoid arthritis: a clinical, serological, and gene polymorphism perspective.

To characterize cumulative joint damage (CJD) patterns in rheumatoid arthritis (RA) and determine their associations with demographic/clinical features and HLA-DRB1 gene polymorphism. Hand and foot radiographs were obtained from 404 patients with RA. CJD patterns were determined by 3 derivations from Sharp/van der Heijde scores, obtained by the mathematical division of scores for hands/feet (Sharp-h/f score), fingers/wrists (Sharp-f/w score), and erosion/space narrowing (Sharp-e/sn score), respectively. DNA and serum were obtained for determination of HLA-DRB1 polymorphism, rheumatoid factor (RF), and anticitrullinated protein antibodies (ACPA). Patients with wrist-dominant CJD pattern were more likely to have severe RA than those with finger-dominant pattern (68.4% vs 46.0%; p = 0.036) as were those with foot-dominant vs hand-dominant CJD pattern (76.5% vs 56.4%; p = 0.044). HLA-DRB1 shared epitope (SE) alleles were associated with erosion-dominant CJD pattern (p = 0.021). Patients with erosion-dominant CJD pattern had higher levels of RF and ACPA than those with space-narrowing-dominant CJD pattern (median RF 71.35 U/ml vs 22.05 U/ml, respectively; p = 0.003; median ACPA 187.9 U/ml vs 143.2 U/ml, respectively; p < 0.001). The majority of triple-positive patients (SE+, RF+, ACPA+) had erosion-dominant CJD pattern (62.3%) while the majority of triple-negative patients (SE-, FR-, ACPA-) had space narrowing-dominant CJD pattern (75%; p = 0.017). ACPA was associated with HLA-DRB1 SE alleles (p < 0.05). Patients with foot-dominant CJD pattern were taller than those with hand-dominant CJD pattern (p = 0.002); those with erosion-dominant CJD pattern had higher weight and body mass index than those with space narrowing-dominant CJD pattern (p = 0.014, p = 0.001). CJD patterns were associated with disease severity, HLA-DRB1 SE status, presence and titer of ACPA and RF, and morphometric features.

Rates of serious infections and malignancies among patients with rheumatoid arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy.

Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy. The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users. Data on infections and malignancies were acquired from national healthcare registers. A Poisson model was used to calculate the adjusted incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis, year of the beginning of the followup, rheumatoid factor status, Disease Activity Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior serious infection, prior biologic use, and time-updated use of methotrexate, sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders. In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63-2.3), 0.84 (95% CI 0.53-1.3), 0.98 (95% CI 0.60-1.6), and 1.1 (95% CI 0.59-1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR. Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.

Lack of autoantibody induction by mercury exposure in artisanal gold mining settings in Colombia: Findings and a review of the epidemiology literature

Mercury (Hg) has been implicated as an immunotoxicant in experimental animal models, but its role in the induction of human autoimmunity remains unclear due to contradictory findings. Therefore, it has been claimed that it is important to examine other populations in order to clarify the role of Hg in these diseases. The aim of this study was to investigate whether occupational Hg exposure due to artisanal gold mining is associated with the prevalence of autoimmune biomarkers. A cross-sectional study was conducted comparing Hg-exposed gold miners (n = 164) with a control population (n = 127). Hair, blood, and 24-h urine samples were collected for measures of Hg levels, as well as of anti-nuclear antibodies (ANA) and rheumatoid factor (RF). Participants were clinically evaluated by a general practice physician, a rheumatologist, and a toxicologist. Statistically significant differences (p < 0.001) were found between Hg-exposed and non-exposed groups for all Hg biomarkers tested: blood (7.03 versus 2.46 µg Hg/L), urine (3.96 versus 1.48 µg Hg/g creatinine), and hair (0.79 versus 0.39 µg Hg/g). No difference was observed in ANA (cut-off titre of 1:80; PR = 0.93, 95% CI = 0.45–1.90) and RF (cut-off = 30 IU/mL; PR = 0.062, 95% CI = 0.03–1.08) status between the groups. In conclusion, the findings here do not support the hypothesis that Hg exposure due to artisanal gold mining activities had a significant impact on autoantibodies as biomarkers of autoimmune diseases. In a review context, the epidemiological findings were interpreted in light of the conflicting data in the literature about how Hg exposure was linked to development of autoantibodies. Validation of these findings in prospective studies is needed to firmly establish the role of Hg in development of autoimmunity in human populations.

Rheumatoid factor and anti-citrullinated protein antibody positivity, but not level, are associated with increased mortality in patients with rheumatoid arthritis: results from two large independent cohorts.

IntroductionThis study aimed to investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA).MethodsData from the Norfolk Arthritis Register (NOAR) and Leiden Early Arthritis Clinic (EAC) cohorts were used. At baseline, patients had demographic data and smoking status recorded; RF, ACPA and inflammatory markers were measured in the local laboratories. Patients were flagged with national death registers until death or censor date. Antibody status was stratified as negative, low or high positive by RF and ACPA levels individually. In addition, patients were grouped as seronegative, RF positive, ACPA positive or double antibody (RF and ACPA) positive. Cox regression models explored associations between antibody status and mortality adjusting for age, sex, smoking status, inflammatory markers and year of enrolment.ResultsA total of 4962 patients were included, 64% were female. Median age at onset was 56 (NOAR) and 54 (EAC) years. In NOAR and EAC respectively, 35% and 42% of patients were ACPA/RF positive. When antibody status was stratified as negative, low or high positive, there were no consistent findings between the two cohorts. Double antibody positivity was associated with excess mortality in both cohorts compared to seronegative patients: NOAR and EAC respective adjusted HR (95% confidence interval) 1.35 (1.09 to 1.68) and 1.58 (1.16 to 2.15).ConclusionsPatients with EIA who are seropositive for both RF and ACPA have increased mortality compared to those who are single positive or seronegative. Antibody level in seropositive patients was not consistently associated with excess mortality.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0483-3) contains supplementary material, which is available to authorized users.

Anti–citrullinated protein antibody positivity correlates with cartilage damage and proteoglycan levels in patients with rheumatoid arthritis in the hand joints.

Objective: To investigate the factors associated with cartilage proteoglycan content in patients with rheumatoid arthritis (RA) Methods: 32 RA patients received high-field 3 Tesla Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) for determining cartilage proteoglycan content. Measurements were performed in three individual cartilage regions (medial, central, lateral) of the metacarpophalangeal joints 2 and 3. dGEMRIC values were then related to disease duration, disease activity, anti-citrullinated protein antibody (ACPA) status, rheumatoid factor status and C-reactive protein level. Results: dGEMRIC values were not significantly different between the MCP2 and MCP3 joint. Inter-class correlations were high (>0.92) for all three (medial, central and lateral) cartilage compartments. dGEMRIC values were significantly lower in RA patients with longer disease duration (≥3 years) and those with ACPA positivity than those with a short disease duration (<3 years)(p=0.034) or negative ACPA (p=0.0002), respectively. In contrast, no association between cartilage proteoglycan content and disease activity, C-reactive protein level and rheumatoid factor status was found. Conclusion: Decreased cartilage proteoglycan content in RA patients is associated with disease duration and ACPA positivity but not with the actual disease activity, CRP level or rheumatoid factor status. These data suggest that the cumulative burden of inflammation as well as ACPA are the determinants for cartilage damage in RA.

Rheumatoid factor mediates excess serum lipoprotein(a) for independent association with type 2 diabetes in men.

Objective:The potential association of rheumatoid factor (RF) and lipoprotein (Lp)(a) levels, as well as with the likelihood of type 2 diabetes and hypertension, needs exploring.Methods:Cross-sectional associations were sought in this unselected and population-based 1539-adult cohort (age 58.8±10.6 years). RF was assayed nephelometrically. Multiple logistic regression analyses were used for covariates of RF positivity and for the latter’s association with diabetes and hypertension.Results:RF-positive individuals were older, fewer current smokers, had significantly lower fasting triglycerides (by 13%), higher fibrinogen, and tended to higher sex hormone-binding globulin (SHBG) levels. Whereas, women had a similar risk profile irrespective of RF status, RF-positive men had significantly higher Lp(a). In contrast to Lp(a) being positively correlated with SHBG in RF-negative subjects (r=0.08; p=0.007), an inverse correlation existed in seropositive individuals (r=-0.32, p=0.011), suggesting the interplay of an immune complex. In regression analyses, RF positivity was associated with Lp(a) in men but not in women, [OR 1.53 (1.19; 1.96)], independent of age, SHBG, and C-reactive protein (CRP). RF positivity was further associated with diabetes [OR 1.98 (95% CI 1.11; 3.52)] in the whole sample, additively to waist circumference and CRIP major determinants of diabetes. RF-positive subjects were not significantly associated independently with hypertension.Conclusion:Autoimmune activation linked to Lp(a) is mediated by the autoantibody RF in contributing to the development of type 2 diabetes.

Response to Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis for Function and Pain is Affected by Rheumatoid Factor.

Objectives : To investigate differences in response to tumor necrosis factor inhibitor treatment (TNFi) in seropositive (rheumatoid factor positive; RF+) versus seronegative (RF-) patients with established RA as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain.Methods : RA patients from an established RA cohort were studied according to rheumatoid factor (RF) status for change in HAQ-DI and pain (0-3 VAS) one year after starting treatment with a TNFi.Results : There were 238 patients treated with TNFi who had follow-up data (178 RF+ and 60 RF-). Disease duration was longer in RF+ vs RF- (12+8 vs 8+8 years) but the proportion of females (82% vs 72%, P=0.7), baseline HAQ-DI (1.44+0.63 vs 1.41+0.63, P=0.8) and pain (1.92+0.67 vs 1.93+0.67, P=0.9) were not different. The mean duration of treatment of first TNFi was 2.8 vs 2.3 years, P=0.1 and 68% of RF+ vs 62% of RF- were still receiving first TNFi at last visit (P=0.5). For patients with data at baseline and one year, the one-year HAQ-DI change was significantly greater in 90 RF+ patients (-0.356) versus 38 RF- patients (-0.126; P=0.04). The mean pain improvement was also greater in 77 RF+ vs 32 RF- patients (-0.725 vs -0.332 respectively; P=0.03). Numbers are small, data are missing and comorbidities, DAS28 and anti-CCP were not collected.Conclusion : Despite limitations in the data, in established RA after failure of DMARDs, RF+ patients may be more responsive to TNFi therapy as measured by changes in HAQ-DI and pain.Innovation : There may be a better response to TNFi in RA if RF positive for function and pain.

A non-synonymous single-nucleotide polymorphism in the gene encoding Toll-like Receptor 3 (TLR3) is associated with sero-negative Rheumatoid Arthritis (RA) in a Danish population

BackgroundIt has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA in a predominantly Caucasian population from Denmark using a case–control approach.FindingsDNA samples (3 university hospital outpatient clinics) were obtained from patients with RA (n = 704) and healthy controls (n = 639) in a Danish population. TLR single nucleotide polymorphisms (SNPs) were selected based on the previously reported associations with chronic autoimmune diseases. Genotyping for the TLR SNPs was performed using Sequenom Multiplex technology.We identified one SNP in TLR3, [(rs3775291, P = 0.02, OR (95% CI) 1.31 (1.1087-1.5493)] significantly associated with the whole RA cohort. Subgroup analysis according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status suggested a significant association of sero-negative RA with the rs3775291 A allele and disease activity in this subset.ConclusionThese observations on a RA population of Danish ancestry suggest that variations in the TLR3 locus may be implicated in the pathogenesis of sero-negative RA. Since this TLR3 SNP has previously been associated with systemic lupus erythematous (SLE), the present findings support the notion that TLR3 genetic variants may represent a common risk factor in different chronic inflammatory conditions, including RA and SLE.

Rheumatoid arthritis is associated with IgG antibodies to human endogenous retrovirus gag matrix: a potential pathogenic mechanism of disease?

Human endogenous retrovirus (HERV)-K10 has been implicated in the etiology and pathogenesis of rheumatoid arthritis (RA). A secondary immune response to this virus might suggest an antigen-driven response in patients. The Gag region of HERV-K10 could provide a key epitope important for immunological reactivity. We investigated the presence of IgG antibodies to this region and assessed its significance in RA. We determined an antigenic peptide on the matrix segment of HERV-K10 and developed an ELISA system to detect IgG antibodies in patients with RA and controls. The presence of antibodies to the matrix peptide (denoted as MAG1: RIGKELKQAGRKGNI) was correlated with patient details. On screening patients' serum, we found a significantly higher mean IgG antibody response to MAG1 in 30 patients with RA as compared to 23 patients with inflammatory bowel disease (p = 0.003), 29 patients with osteoarthritis (p = 0.001), and 43 healthy individuals (p = 0.002). Reactivity was not observed to a control peptide possessing a nonhomologous amino acid sequence. On evaluating clinical details with serological activity, no correlation with disease duration (p = 0.128), sex (p = 0.768), or rheumatoid factor status (p = 0.576) was found. A significantly elevated IgG antibody response to an HERV-K10 Gag matrix peptide was observed in patients with RA, suggesting that the exposure of HERV-K10 may cause a secondary, antigenic driven immune response in RA.

An updated meta-analysis of the signal transducer and activator of transcription 4 (STAT4) rs7574865 G/T polymorphism and rheumatoid arthritis risk in an Asian population

Objectives: Signal transducer and activator of transcription 4 (STAT4) transmits signals induced by the cytokines interleukin (IL)-12, IL-23, and interferon (IFN)-γ, which play an important role in the development of rheumatoid arthritis (RA). Studies have shown conflicting results concerning the association between the rs7574865 G/T polymorphism in the STAT4 gene and RA in an Asian population. We have performed a meta-analysis to examine this relationship.Method: We searched PubMed and WanFang databases for all papers published up to 5 October 2013. Eight case–control studies with 6029 cases and 4685 controls were retrieved based on the search criteria for RA susceptibility related to the STAT4 rs7574865 G/T polymorphism. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed using Begg’s test.Results: A significant association was found between the STAT4 rs7574865 G/T polymorphism and RA risk (e.g. GG+GT vs. TT: RR 0.96, 95% CI 0.95–0.97; GG+TT vs. GT: RR 0.94, 95% CI 0.91–0.97). Subgroup analysis of rheumatoid factor (RF) status revealed a protective relationship between the STAT4 rs7574865 G/T polymorphism and RF+/RF− RA risk. A similar relationship was detected in the anti-cyclic citrullinated peptide (CCP) status subgroup. No clear evidence of publication bias was detected in the overall analysis.Conclusions: Our study indicates that the STAT4 rs7574865 G/T polymorphism was significantly associated with a decreased RA risk in an Asian population.