Altered Antibody Response to Epstein-Barr Virus in Patients With Rheumatoid Arthritis and Healthy Subjects Predisposed to the Disease. A Twin Study.

To study Epstein-Barr virus (EBV) antibody patterns in twin individuals with rheumatoid arthritis (RA) and their healthy co-twins, and to determine the heritability of antibody responses against the EBV encoded EBNA1 protein. Isotypes of EBNA1 antibodies were measured in 137 RA affected- and 150 healthy twin pairs. We estimated the effect of RA and RA predisposition, anti-citrullinated antibodies (ACPA), IgM rheumatoid factor (RF), the shared epitope (SE) and the PTPN22-T allele (PTPN22) on the level of EBNA1 antibodies.

White blood cell mitochondrial DNA copy number is decreased in rheumatoid arthritis and linked with risk factors. A twin study.

Low mitochondrial DNA copy number (mtDNA CN) has been associated with e.g. cancer, cardiovascular and autoimmune diseases.

Twin DNA Methylation Profiling Reveals Flare-Dependent Interferon Signature and B Cell Promoter Hypermethylation in Systemic Lupus Erythematosus.

Objective: Systemic lupus erythematosus (SLE) has limited monozygotic twin concordance, implying a role for pathogenic factors other than genetic variation, such as epigenetic changes. Using the disease-discordant twin model, we investigated genome-wide DNA methylation changes in sorted CD4+ T cells, monocytes, granulocytes, and B cells in twin pairs with at least 1 SLE-affected twin.

Methods: Peripheral blood obtained from 15 SLE-affected twin pairs (6 monozygotic and 9 dizygotic) was processed using density-gradient centrifugation for the granulocyte fraction.

Concordance of autoimmune disease in a nationwide Danish systemic lupus erythematosus twin cohort.

Objective: To determine the concordance of systemic lupus erythematosus (SLE) and co-aggregating autoimmune diseases among Danish twins.

Methods: SLE-affected twins were ascertained by record linkage between the National Patient Register (NPR) and the Danish Twin Registry (DTR). Registered SLE codes were validated through medical chart review and information from the treating physicians.

Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study.

Objectives: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA.

Methods: Genomic DNA was isolated from whole blood samples from 28 MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips.

Incidence of Chronic Persistent Rheumatoid Arthritis and the Impact of Smoking: A Historical Twin Cohort Study.

Objective: To assess the incidence of chronic persistent rheumatoid arthritis (RA) in a population-based cohort of twins and to determine the impact of smoking.

Methods: In a historical cohort study on twins born in 1920 to 1982, we identified 157 cases of RA among 45,280 responders (response rate 80%). Information on smoking was obtained by questionnaire and interview.

Low-field magnetic resonance imaging or combined ultrasonography and anti-cyclic citrullinated peptide antibody improve correct classification of individuals as established rheumatoid arthritis: results of a population-based, cross-sectional study.

Background: The aim of the present study was to evaluate the accuracy of two approaches using magnetic resonance imaging (MRI) or combined ultrasonography (US) and anti-cyclic citrullinated peptide antibody (ACPA) for diagnosis and classification of individuals with established rheumatoid arthritis (RA).

Methods: In 53 individuals from a population-based, cross-sectional study, historic fulfilment of the American College of Rheumatology (ACR) 1987 criteria ("classification") or RA diagnosed by a rheumatologist ("diagnosis") were used as standard references. The sensitivity, specificity and Area under Curve for Receiver Operating Characteristics curves (ROC-area: (sensitivity + specificity)/2) were calculated for "current fulfilment of the ACR 1987 criteria" (list format), "adapted ACR 1987 criteria" (list format, substituting IgM rheumatoid factor with ACPA and clinical joint swelling and erosions on radiography with synovitis and erosions detected by US on a semi-quantitative scale), and RA MRI scoring System (RAMRIS) scores on low-field MRI in the unilateral hand.

Newborn infant characteristics and risk of future rheumatoid arthritis: a twin-control study.

Low birth weight has been proposed as a risk factor for rheumatoid arthritis (RA). The twin-control study design provides an opportunity to investigate the significance of potential prenatal determinants for adult morbidity by accounting for maternal characteristics and early environmental and genetic factors. We investigated the association between birth weight and RA in a sample of 42 twin pairs discordant for rheumatoid arthritis in which valid information on birth weight, birth length, and order was available from midwife records.

On the origin of rheumatoid arthritis: the impact of environment and genes--a population based twin study.

Background: Rheumatoid arthritis (RA) is an autoimmune disease with a complex origin. Previous studies have reported heritability estimates on RA at about 60%. Only 16% of the genetic background of the disease has been disclosed so far.

The impact of genes on the occurrence of autoantibodies in rheumatoid arthritis. A study on disease discordant twin pairs.

Objective: To assess the genetic effect on the occurrence of rheumatoid arthritis (RA) associated autoantibodies.

Methods: A co-twin control study of 27 monozygotic (MZ) and 51 dizygotic same sexed (DZss) RA discordant twins.

Outcome Measures: The probandwise concordance rate of anti-keratin antibodies (AKA), anti-cyclic citrullinated peptide antibodies (ACPA), IgA- and IgM rheumatoid factor (IgA-RF and IgM-RF).

Prevalence of rheumatoid arthritis in the southern part of denmark.

The aim of the present study was to estimate the prevalence of rheumatoid arthritis in the southern part of Denmark. Using a screening questionnaire, telephone interview, register data, and a clinical examination cases were ascertained from a random sample of 4995 individuals over the age of 15. As case definition we used the original and modified 1987 American College of Rheumatology classification criteria.

Uncoupling of collagen II metabolism in newly diagnosed, untreated rheumatoid arthritis is linked to inflammation and antibodies against cyclic citrullinated peptides.

Objective: To investigate the relationship between markers of collagen II synthesis and degradation with disease activity measures, autoantibodies, and radiographic outcomes in a 4-year protocol on patients with early rheumatoid arthritis (RA) who are naïve to disease-modifying antirheumatic drugs.

Methods: One hundred sixty patients with newly diagnosed, untreated RA entered the Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA) trial. Disease activity and radiograph status were measured at baseline and 4 years.

Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis.

Objective: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA).

Methods: Patients with early RA (n=158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position -221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score).

Results: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2 high producers (YA/YA).

Incidence of rheumatoid arthritis from 1995 to 2001: impact of ascertainment from multiple sources.

The aim of this study was to describe the mean incidence rate of rheumatoid arthritis over a 7-year period from 1995 to 2001 in a population in the southern part of Denmark, using the data from several sources. Cases fulfilling the 1987 American College of Rheumatology criteria for rheumatoid arthritis were identified at hospitals and private practising rheumatologists (referral centres), and in general practice. The observed incidence was 32/100,000 person-years (95% confidence interval 29-35).

[The importance of physical activity and body mass index for body satisfaction].

Introduction: Body satisfaction has mostly been investigated among patients with psychiatric diseases. A few studies have found an association between physical activity, obesity and body satisfaction in the healthy population, but the focus has mostly been on the risk of developing diseases. The aim of the present study has been to study the association between body satisfaction, BMI, physical activity and chronic diseases.

Incidence of Rheumatoid Arthritis in the Southern part of Denmark from 1995 to 2001.

We estimated the incidence of rheumatoid arthritis in the southern part of Denmark from 1995 to 2001. At a rheumatology hospital serving a population of about 200 000 people over the age of 15, medical records were scrutinized. As case definition we used the tree and list format of 1987 American College of Rheumatology criteria for rheumatoid arthritis.

Twin study of genetic and aging effects on X chromosome inactivation.

To investigate the genetic influence on X chromosome inactivation and on age-related skewing of X inactivation, in particular, we analysed the X inactivation pattern (XIP) in peripheral blood cells from 118 young monozygotic (MZ) twin pairs (18-53 years), 82 elderly MZ twin pairs (55-94 years), 146 young dizygotic (DZ) twin pairs (20-54 years) and 112 elderly DZ twin pairs (64-95 years). Elderly twins had a higher frequency of skewed X inactivation (34%) than young twins (15%) (P<0.001).

Validity of rheumatoid arthritis diagnoses in the Danish National Patient Registry.

Discharge diagnoses following hospital admissions in Denmark are recorded in the Danish National Patient Registry (NPR). Such routine hospitalization records may serve as useful research tools in epidemiological studies. The aim of the study was to provide measures of the validity and completeness of rheumatoid arthritis (RA) diagnoses recorded in the NPR.

Relative importance of genetic effects in rheumatoid arthritis: historical cohort study of Danish nationwide twin population.

Objective: To determine the relative importance of environmental and genetic effects in the development of rheumatoid arthritis.

Design: Historical cohort study with record linkage between a twin registry and the Danish discharge registry as well as the Danish national registry of deaths used to estimate completeness.

Setting: Two population based nationwide twin birth cohorts.