Maintenance of cytomegalovirus-specific CD4pos T-cell response in rheumatoid arthritis patients receiving anti-tumor necrosis factor treatments

International audienceINTRODUCTION: Anti-tumor necrosis factor (TNF)-α biotherapies have considerably changed the treatment of rheumatoid arthritis (RA). However, serious infections are a major concern in patients with rheumatic diseases treated with anti-TNF-α. Little is known about viral, especially latent, infections in anti-TNF-α treatments. Infections by cytomegalovirus (CMV), a β-herpes virus, are frequent and induce a strong CD4pos T-cell immunity, which participates in the control of infection. We thus have chosen to analyze the CD4pos T-cell response to CMV antigens as a model of antiviral response in RA patients treated with anti-TNF-α. CD28 expression was evaluated. METHODS: We have measured the CD4pos response to CMV antigens in RA patients, before and after initiation of treatment with an anti-TNF-α agent. The intracellular production of interferon (IFN)-γ in total and CD28neg CD4pos T cells in response to CMV antigens (Ags) was evaluated with flow cytometry. The proliferation of total CD4pos T cells in the presence of CMV antigens was measured with 3H-thymidine incorporation. RESULTS: Anti-TNF-α treatments impaired neither the anti-CD4pos anti-CMV IFN-γ response nor the proliferative response in patients. The percentage of CD28neg CD4pos cells remained constant. CONCLUSIONS: Our data suggest that the CD4pos T-cell response against CMV is not altered by anti-TNF-α treatments and that infection remains controlled in treated RA patients latently infected with CMV. Our observation brings new insight into the current knowledge of the risks of infection in patients treated with anti-TNF-α biotherapies

Relationships between ultrasound enthesitis, disease activity and axial radiographic structural changes in patients with early spondyloarthritis: data from DESIR cohort

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Aiming for SDAI remission versus low disease activity at 1 year after inclusion in ESPOIR cohort is associated with better 3-year structural outcomes

International audienceOBJECTIVES: Using data for patients with early rheumatoid arthritis (RA) from the ESPOIR cohort, we aimed to evaluate the impact of remission versus low disease activity (LDA) by the Simple Disease Activity Index (SDAI) at 1 year on 3-year structural damage assessed by the modified Sharp-van der Heijde total score (mTSS) and functional impairment assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI). METHODS: We included 625 patients from the ESPOIR cohort who fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and had an SDAI score at 1 year. mTSS and HAQ-DI scores were compared at 3 years for patients with SDAI remission or LDA status at 1 year. A linear mixed model was used to assess the independent effect of SDAI status at 1 year on mTSS and HAQ-DI at 3 years. RESULTS: Of the 625 patients included (mean (SD) age 48.5 (12.1) years; 491 (78.6%) were women), 121 (19.4%) were in SDAI remission and 223 (35.7%) in LDA at 1 year. The mean (SD) mTSS and HAQ-DI score at 3 years was 9.6 (9.2) and 0.23 (0.42), respectively, for patients in remission at 1 year and 15.8 (16.1) and 0.43 (0.52), respectively, for patients with LDA (both p<0.05). Multivariate analysis revealed an association of remission rather than LDA status at 1 year and reduced mTSS score (p=0.005) but not HAQ-DI score (p=0.4) at 3 years. CONCLUSIONS: Aiming for SDAI remission rather than LDA at 1 year leads to better radiographic outcomes at 3 years in early RA patients

Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts).

International audienceTo assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients.This work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions.The AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14-3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68-6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94-18.69], p = 0.002) on the risk of erosions in ACPA+ patients.A haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA

Link between traditional cardiovascular risk factors and inflammation in patients with early arthritis: results from a French multicenter cohort.

International audienceOBJECTIVE: To compare the characteristics of traditional cardiovascular risk factors for untreated patients with early arthritis (EA) and healthy subjects, and to look for a link between cardiovascular risk factors and inflammation in EA patients.METHODS: This multicenter case-control study enrolled 607 patients with EA (ESPOIR cohort) and 1,821 age- and sex-matched controls (World Health Organization MONICA survey). Lipid levels, blood pressure, glucose levels, and exposure to smoking were characterized in patients and controls. Systemic inflammation was quantified in EA patients. Traditional cardiovascular risk factor characteristics were compared between patients with EA and controls. The link between cardiovascular risk factors and inflammation was assessed in EA patients.RESULTS: Mean ± SEM total cholesterol (2.14 ± 0.022 versus 2.34 ± 0.017 gm/liter; P < 0.001), high-density lipoprotein (HDL) cholesterol (0.60 ± 0.011 versus 0.63 ± 0.007 gm/liter; P = 0.020), and low-density lipoprotein (LDL) cholesterol (1.28 ± 0.025 versus 1.51 ± 0.016 gm/liter; P < 0.001) were lower in EA patients than in controls. Triglycerides, triglycerides/HDL ratio, and pulse pressure were higher in patients with EA. Diastolic blood pressure and glucose levels were lower in EA patients. Former or current smokers were more frequent in patients with EA. Total and HDL cholesterol levels were negatively associated with C-reactive protein or serum interleukin-6 levels.CONCLUSION: Total, HDL, and LDL cholesterol, triglycerides, diastolic blood pressure, pulse pressure, glucose, and triglycerides/HDL ratio differ between patients with EA and controls. Some of these risk factors appear to be linked to systemic inflammation. Such initial differences could modulate the risk of cardiovascular events later in the course of arthritis

Impact of Body Mass Index on the Agreement Between Ultrasound- and Clinical Assessments of Disease Activity in Rheumatoid Arthritis : Multicenter and Cross-sectional Study

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Impact of Body Mass Index on the Agreement Between Ultrasound- and Clinical Assessments of Disease Activity in Rheumatoid Arthritis : Multicenter and Cross-sectional Study

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A new classification of HLA-DRB1 alleles based on acid-base properties of the amino acids located at positions 13, 70 and 71: impact on ACPA status or structural progression, and meta-analysis on 1235 patients with rheumatoid from two cohorts (ESPOIR and EAC cohort).

International audienceObjective: To group HLA-DRB1 alleles based on acid–base properties of amino acids at positions 13, 70 and 71 and analyse their association with the presence of anticitrullinated peptide antibodies (ACPA) and structural progression in 2 cohorts of early rheumatoid arthritis (RA).Methods: Patients with RA (N=612) from ESPOIR cohort and from EAC cohort (n=624) were genotyped for HLA-DRB1 alleles. The alleles containing the RAA sequence at positions 72–74 were classified into 3 groups according to the amino acid at positions 13, 70 and 71: BB encoding basic amino acids at positions 13, 70 and 71; A encoding acidic amino acids at positions 70 and 71; and BN encoding either neutral amino acids at position 13 and basic amino acids at positions 70 and 71, or basic amino acid at position 13 and neutral amino acids at positions 70 and 71. The associations between the different alleles and (1) the ACPA presence, and (2) the structural progression were assessed by χ2 test; a meta-analysis was performed on the 2 cohorts using the Mantel-Haenszel method.Results: After meta-analysis, BB alleles were significantly associated with ACPA presence (OR (95% CI) 4.08 (3.14 to 5.31)) and structural progression (OR (95% CI) 2.33 (1.76 to 3.09)). The alleles protected significantly against ACPA presence (OR (95% CI) 0.37 (0.28 to 0.50)) and structural progression (OR (95% CI) 0.34 (0.23 to 0.50)). This acid–base classification allowed to separate another group BN with an intermediate risk of ACPA production (OR (95% CI) 1.14 (0.91 to 1.44)) and structural progression (OR (95% CI) 1.01 (0.77 to 1.33)).Conclusions: This new classification permitted to make a hierarchy of HLA-DRB1 alleles in terms of association with ACPA presence or structural progression in early R

Validation of the 2010-ACR/EULAR – classification criteria using newly EULAR-defined erosion for rheumatoid arthritis on the very early arthritis community-based (VErA) cohort

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