Identification of a genetic variant for joint damage progression in autoantibody-positive rheumatoid arthritis.

Background: Joint destruction is a hallmark of autoantibody-positive rheumatoid arthritis (RA), though the severity is highly variable between patients. The processes underlying these interindividual differences are incompletely understood.

Methods: We performed a genome-wide association study on the radiological progression rate in 384 autoantibody-positive patients with RA.

Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage.

Autoimmune responses against posttranslationally modified antigens are a hallmark of several autoimmune diseases. For example, antibodies against citrullinated protein antigens (ACPA) have shown their relevance for the prognosis and diagnosis of rheumatoid arthritis (RA), and have been implicated in disease pathogenesis. It is conceivable that other autoantibody systems, recognizing other posttranslationally modified proteins, are also present in RA.

Distinct ACPA fine specificities, formed under the influence of HLA shared epitope alleles, have no effect on radiographic joint damage in rheumatoid arthritis.

Objectives: Human leucocyte antigen shared epitope (SE) alleles are associated with joint destruction, the presence of anticitrullinated protein antibodies (ACPA) and the ACPA fine specificity repertoire in rheumatoid arthritis (RA). A large variation in joint destruction is seen within the ACPA-positive patient population, and it is conceivable that certain ACPA reactivities contribute to radiological damage. The authors investigated whether ACPA fine specificities, which are formed under the influence of SE alleles, associate with the extent of radiographic joint damage.

Baseline serum adipokine levels predict radiographic progression in early rheumatoid arthritis.

Objective: Adipose tissue can secrete soluble mediators (adipokines) with potent immune regulatory functions. Some adipokines have been previously associated with radiographic damage in patients with rheumatoid arthritis (RA). In the present study, we investigated the capacity of baseline adipokine levels to predict radiographic progression over a period of 4 years and studied their contribution relative to that of other known risk factors, such as anti-cyclic citrullinated peptide (anti-CCP) antibodies.

Identification of CXCL13 as a marker for rheumatoid arthritis outcome using an in silico model of the rheumatic joint.

Objective: Rheumatoid arthritis (RA) is characterized by inflammation and joint destruction, with the degree of damage varying greatly among patients. Prediction of disease severity using known clinical and serologic risk factors is inaccurate. This study was undertaken to identify new serologic markers for RA severity using an in silico model of the rheumatic joint.

Long-term impact of delay in assessment of patients with early arthritis.

Objective: During the last decade, rheumatologists have learned to initiate disease-modifying antirheumatic drugs (DMARDs) early to improve the outcome of rheumatoid arthritis (RA). However, the effect of delay in assessment by a rheumatologist on the outcome of RA has scarcely been explored. The purpose of this study was to examine the association between delay in assessment by a rheumatologist, rates of joint destruction, and probability of achieving DMARD-free remission in patients with RA.

Predicting arthritis outcomes--what can be learned from the Leiden Early Arthritis Clinic?

Objectives: In order to allow personalized medicine, adequate prediction of disease outcome is required. In early undifferentiated arthritis (UA), prediction of the development of RA is crucial, and in case of RA predicting the severity of the disease course may guide individualized treatment decisions.

Methods: A total of 570 UA patients and 676 RA patients included in the Leiden Early Arthritis Clinic cohort were studied for baseline characteristics.

The ACPA isotype profile reflects long-term radiographic progression in rheumatoid arthritis.

Background: The presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been shown to consist of various isotypes, but the consequences of differences in isotype distribution have not been extensively investigated.

Objective: To investigate the relationship between ACPA isotypes, disease progression and radiological outcome.

Value of anti-modified citrullinated vimentin and third-generation anti-cyclic citrullinated peptide compared with second-generation anti-cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis.

Objective: Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPAs) determined by testing with second-generation anti-cyclic citrullinated peptide (anti-CCP-2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third-generation anti-CCP (anti-CCP-3) and anti-modified citrullinated vimentin (anti-MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease-modifying antirheumatic drug (DMARD)-free remission in RA.

Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis.

Objective: The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14.

Repair of joint erosions in rheumatoid arthritis: prevalence and patient characteristics in a large inception cohort.

Background: Joint destruction in rheumatoid arthritis (RA) was until recently seen as an irreversible state. Lately, it was found that repair of bone erosions occurs; however, little is known about its prevalence.

Objective: To investigate the frequency of repair and patients' characteristics associated with repair in an inception cohort.

Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis.

Background: Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor alpha-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-kappaB and is involved in inhibiting TNF-receptor-mediated signalling effects.