Development of type 1 diabetes in a patient treated with anti-TNF-α therapy for active rheumatoid arthritis

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Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate

Contains fulltext : 80996.pdf (publisher's version ) (Closed access)OBJECTIVE: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). METHODS: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on the two DAS28 definitions were examined. Trends in radiographic progression (erosion score, joint space narrowing score and total score) and physical function (Health Assessment Questionnaire Disability Index (HAQ-DI)) across the EULAR responder states (none, moderate and good) were analysed. RESULTS: There was general agreement in determining the EULAR responder state using both DAS28 definitions (kappa = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: kappa = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. CONCLUSIONS: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis

Model-based data analysis of individual human postprandial plasma bile acid responses indicates a major role for the gallbladder and intestine

BACKGROUND: Bile acids are multifaceted metabolic compounds that signal to cholesterol, glucose, and lipid homeostasis via receptors like the Farnesoid X Receptor (FXR) and transmembrane Takeda G protein-coupled receptor 5 (TGR5). The postprandial increase in plasma bile acid concentrations is therefore a potential metabolic signal. However, this postprandial response has a high interindividual variability. Such variability may affect bile acid receptor activation. METHODS: In this study, we analyzed the inter- and intraindividual variability of fasting and postprandial bile acid concentrations during three identical meals on separate days in eight healthy lean male subjects using a statistical and mathematical approach. MAIN FINDINGS: The postprandial bile acid responses exhibited large interindividual and intraindividual variability. The individual mathematical models, which represent the enterohepatic circulation of bile acids in each subject, suggest that interindividual variability results from quantitative and qualitative differences of distal active uptake, colon transit, and microbial bile acid transformation. Conversely, intraindividual variations in gallbladder kinetics can explain intraindividual differences in the postprandial responses. CONCLUSIONS: We conclude that there is considerable inter- and intraindividual variation in postprandial plasma bile acid levels. The presented personalized approach is a promising tool to identify unique characteristics of underlying physiological processes and can be applied to investigate bile acid metabolism in pathophysiological conditions

The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study

The integrin αvβ3, whose αv subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population

Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study

INTRODUCTION: A candidate gene approach, in a large case-control association study in the Dutch population, has shown that a 480 kb block on chromosome 4q27 encompassing KIAA1109/Tenr/IL2/IL21 genes is associated with rheumatoid arthritis. Compared with case-control association studies, family-based studies have the added advantage of controlling potential differences in population structure. Therefore, our aim was to test this association in populations of European origin by using a family-based approach. METHODS: A total of 1,302 West European white individuals from 434 trio families were genotyped for the rs4505848, rs11732095, rs6822844, rs4492018 and rs1398553 polymorphisms using the TaqMan Allelic discrimination assay (Applied Biosystems). The genetic association analyses for each SNP and haplotype were performed using the Transmission Disequilibrium Test and the genotype relative risk. RESULTS: We observed evidence for association of the heterozygous rs4505848-AG genotype with rheumatoid arthritis (P = 0.04); however, no significance was found after Bonferroni correction. In concordance with previous findings in the Dutch population, we observed a trend of undertransmission for the rs6822844-T allele and rs6822844-GT genotype to rheumatoid arthritis patients. We further investigated the five SNP haplotypes of the KIAA1109/Tenr/IL2/IL21 gene region. We observed, as described in the Dutch population, a nonsignificant undertransmission of the AATGG haplotype to rheumatoid arthritis patients. CONCLUSIONS: Using a family-based study, we have provided a trend for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in populations of European descent. Nevertheless, we failed to replicate a significant association of this region in our rheumatoid arthritis family sample. Further investigation of this region, including detection and testing of all variants, is required to confirm rheumatoid arthritis association

A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Introduction. Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods. We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, aminoacid residues and single nucleotide polymorphisms was undertaken. Results. The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two aminoacid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions. Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition

Internal branding in universities and the lessons learnt from the past: the significance of employee brand support and transformational leadership

The paper reviews the literature on the concept of internal branding and its effects in the service sector in general, as well as in UK universities. In addition, the concept of employee brand support is reviewed, discussing the influence of leadership characteristics on internal branding in universities. Employee brand support is a crucial element to successful internal branding activities. A great concern is that the knowledge of internal branding and employee brand support in higher education institutions is based on knowledge imported from the business sector, and more practices should thus be adapted and implemented. It is found that transformation leadership, despite being little researched in the internal branding context, remains the pivotal element to the successful implementation of internal branding, as transformational leadership provides space for intellectual stimulation and consideration of individuals that are present at universities. Potential future research areas for internal branding studies are identified and discussed