Progression of joint damage in early rheumatoid arthritis: Association with HLA–DRB1, rheumatoid factor, and anti–citrullinated protein antibodies in relation to different treatment strategies

Vries-Bouwstra, Jeska K de; Goekoop-Ruiterman, Yvonne P M; Verpoort, Kirsten N; Schreuder, G. M. T.; Ewals, J. A. P. M.; Terwiel, J. P.; Ronday, H.K.; Kerstens, P.; Toes, René E. M.; Vries, R. R. P. De; Breedveld, Ferdinand C.; Dijkmans, B.A.C.; Huizinga, T.; Allaart, Cornelia F

doi:10.1002/art.23439

Cited by 93 publications

(66 citation statements)

References 17 publications

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“…The classic SE at the DR locus had no influence on the development of erosive disease or on the progression to severe disease. Previous studies of SE alleles in EPA patients have reached similar conclusions about the SE, possibly because current treatments alter its influence on severity (31)(32)(33)35,36). Analysis of the characteristics of patients with early aggressive erosive disease deserves more focused research since close to 75% of such patients reached the severe disease threshold by 30 months despite aggressive treatment with nonbiologic DMARDs.…”

Section: Discussionmentioning

confidence: 83%

The DERAA HLA–DR alleles in patients with early polyarthritis: Protection against severe disease and lack of association with rheumatoid arthritis autoantibodies

Carrier¹,

Cossette²,

Chartier³

et al. 2009

Arthritis & Rheumatism

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Objective. To define the association of alleles encoding the HLA-DR rheumatoid arthritis (RA) protective epitope (DERAA) with the presence of RAassociated antibodies at study inclusion and with severe outcome in patients with early polyarthritis (EPA).Methods. Consecutive EPA patients (n ‫؍‬ 210) were evaluated early (mean of 4.8 months after diagnosis) and prospectively (for 30 months). HLA class II typing was performed by polymerase chain reaction using sequence-specific primers, and HLA-DR alleles DERAA, RA-associated shared epitope (SE), and non-SE/non-DERAA (neither SE nor DERAA) were identified. RA-associated antibodies identified were anti-Sa/ citrullinated vimentin, anti-cyclic citrullinated peptide 2, and IgM rheumatoid factor. Severe disease was defined according to a preset threshold of joint destruction and/or functional limitation.Results. DERAA and SE alleles were present in 62 and 110 of the 210 EPA patients, respectively. At 30 months, severe disease was present in 78 patients (37%). In contrast to SE alleles, DERAA alleles were not associated with the production of RA-associated antibodies, but were strongly protective against severe disease at 30 months (odds ratio 0.30, P < 0.001). DERAA alleles emerged as a strong, independent protective marker on multivariate analysis. The protective effect of DERAA was seen only in patients who did not already have erosions at study inclusion, was independent of the presence of antibodies, but was not associated with spontaneous remission.Conclusion. In our EPA cohort, the presence of a DERAA sequence was a strong independent predictor of a better prognosis, but only in the absence of erosive disease that was already present at inclusion. Identification of DERAA alleles may help in managing the large subgroup of EPA patients who do not have erosions at baseline.

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Section: Discussionmentioning

confidence: 83%

The DERAA HLA–DR alleles in patients with early polyarthritis: Protection against severe disease and lack of association with rheumatoid arthritis autoantibodies

Carrier¹,

Cossette²,

Chartier³

et al. 2009

Arthritis & Rheumatism

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“…Clinical studies show that positive anti-CCP is associated more frequently with radiographic progression. In the BeST study, radiographic progression scores were much higher in patients treated with sequential monotherapy 10 , and ACPA positivity better predicted progressive disease in this monotherapy treatment arm versus RF positivity (odds ratio 12.6, 95% confidence interval 3.0-51.9 for ACPA, compared to OR 4.7, 95% CI 1.5-14.5 for RF).…”

Section: Rheumatologymentioning

confidence: 96%

Anti-Cyclic Citrullinated Peptide Antibody versus HAQ/MDHAQ: Comparing Apples and Oranges?

Bykerk¹

2009

J Rheumatol

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“…The shared epitope has long been known to be associated with the occurrence of RA (de Vries-Bouwstra et al, 2008).…”

Section: Shared Epitopes As Part Of Innate Immunitymentioning

confidence: 99%

Innate immunity, epigenetics and autoimmunity in rheumatoid arthritis

Rodrigues

Jüngel

2009

Molecular Immunology

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by the progressive and irreversible destruction of joints.RA remains an incurable condition, although a new class of drugs, biologicals, have made a major breakthrough in targeting and/or eliminating the immune cells, including T cells, B cells and monocytes/macrophages from the joints. That we cannot (yet?) cure the disease is most likely due to the lack of therapeutic targeting the endogenously activated RA synovial fibroblasts (RASF).Most interestingly, RASF express Toll-like receptors 1-6 rendering them prone to activation by exogenous and endogenous TLR ligands and resulting in the production of numerous powerful chemokines and cytokines. These factors are responsible for the repopulation of immune cells in the joints after ceasing cell depleting therapies.To characterize the molecular mechanisms of synovial activation, a new approach studying the epigenetic characteristics of RASF has been recently undertaken.Thereby, the pattern of histone acetylation, DNA methylation and gene expression regulating microRNA are being explored.Since auto-antibodies have the most predictive and diagnostic value for RA, it is challenging to study more comprehensively the contribution of auto-antibodies to the disease. A new screening technique, serological analysis of recombinant human cDNA expression library (SEREX), adapted from cancer research allowed for the identification of novel auto-antibodies in RA, including anti-serpin E2 auto-antibodies.The serpin E2 auto-antibodies were found to inhibit the activity of serpin E2 and have potentially a functional role in the disease. The recent findings in the field of innate immunity, epigenetics and autoimmunity related to the pathogenesis of RA are in the scope of this review. 2

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Progression of joint damage in early rheumatoid arthritis: Association with HLA–DRB1, rheumatoid factor, and anti–citrullinated protein antibodies in relation to different treatment strategies

Cited by 93 publications

References 17 publications

The DERAA HLA–DR alleles in patients with early polyarthritis: Protection against severe disease and lack of association with rheumatoid arthritis autoantibodies

The DERAA HLA–DR alleles in patients with early polyarthritis: Protection against severe disease and lack of association with rheumatoid arthritis autoantibodies

Anti-Cyclic Citrullinated Peptide Antibody versus HAQ/MDHAQ: Comparing Apples and Oranges?

Innate immunity, epigenetics and autoimmunity in rheumatoid arthritis

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