Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression

Rönnelid, Johan; Wick, Marius C.; Lampa, Jon; Lindblad, Staffan; Nordmark, Birgitta; Klareskog, Lars; Vollenhoven, R F van

doi:10.1136/ard.2004.033571

Cited by 299 publications

(268 citation statements)

References 21 publications

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“…There was no difference in treatment regimens between the 2 groups. These data confirm that clinical disease activity is similar in ACPAϩ and ACPA-RA patients, even if the former subset has a worse prognosis in terms of structural damage (15,16). Similar levels of inflammation and T cell infiltration in ACPA؉ and ACPA-RA synovitis.…”

Section: Resultssupporting

confidence: 68%

“…At the clinical level, several studies have consistently indicated that the presence of ACPAs is associated with more-severe joint destruction over time (15,16). In contrast, the clinical presentation and disease severity are not different between ACPAϩ and ACPApatients and the difference in the severity of joint destruction holds true only at the group level, with an important overlap between the two subsets at the individual level.…”

mentioning

confidence: 99%

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Alterations of the synovial T cell repertoire in anti–citrullinated protein antibody–positive rheumatoid arthritis

Cantaert¹,

Brouard²,

Thurlings³

et al. 2009

Arthritis & Rheumatism

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Objective. The association of HLA-DRB1 alleles with anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) suggests the potential involvement of T lymphocytes in ACPA-seropositive disease. The purpose of this study was to investigate this hypothesis by systematic histologic and molecular analyses of synovial T cells in ACPA؉ versus ACPA-RA patients.Methods. Synovial biopsy samples were obtained from 158 RA patients. Inflammation was determined histologically and immunohistochemically. RNA was extracted from peripheral blood mononuclear cells and synovial tissues obtained from 11 ACPA؉ RA patients, 7 ACPA-RA patients, and 10 spondylarthritis (SpA) patients (arthritis controls). T lymphocyte clonality was studied by combined quantitative and qualitative T cell receptor CDR3 length distribution (LD) analysis and direct sequencing analysis.Results. ACPA؉ and ACPA-RA patients were similar at both the clinical and histologic levels. At the molecular level, however, patients with ACPA؉ synovitis displayed a marked elevation of qualitative CDR3 LD alterations as compared with those with ACPA-synovitis and with the SpA controls. These differences in CDR3 LD were not observed in the peripheral blood, indicating a selective recruitment and/or local expansion of T cells in the synovial compartment. The CDR3 LD alterations reflected true monoclonal or oligoclonal expansions, as confirmed by direct sequencing of the T cell receptor. The CDR3 LD alterations in RA synovium did not correlate with B cell clonal expansions but were inversely associated with synovial lymphoid neogenesis.Conclusion. The T cell repertoire is specifically restricted in RA patients with ACPA؉ synovitis. Whereas the origin and role of these clonal alterations remain to be determined, our data suggest the preferential involvement of T lymphocytes in ACPAseropositive RA.

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Section: Resultssupporting

confidence: 68%

mentioning

confidence: 99%

Alterations of the synovial T cell repertoire in anti–citrullinated protein antibody–positive rheumatoid arthritis

Cantaert¹,

Brouard²,

Thurlings³

et al. 2009

Arthritis & Rheumatism

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“…The presence of ACPA was determined using the Immunoscan RA Mark 2 enzyme-linked immunosorbent assay test (EuroDiagnostica), as described previously (26). ACPA was considered present if the serum antibody level was Ͼ25 units/ ml.…”

Section: Methodsmentioning

confidence: 99%

Association between body mass index and anti–citrullinated protein antibody–positive and anti–citrullinated protein antibody–negative rheumatoid arthritis: Results from a population‐based case–control study

Wesley¹,

Bengtsson²,

Elkan³

et al. 2012

Arthritis Care & Research

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Objective. Being overweight or obese is associated with many chronic diseases, but previous studies of the association with rheumatoid arthritis (RA) have shown inconsistent results. The aim of this study was to investigate the association between body mass index (BMI) and the risk of developing the 2 main subtypes of RA. Methods. At inclusion, cases and controls answered questions about their weight and height and donated blood samples. The presence of antibodies to citrullinated protein antigens (ACPAs) was analyzed among 2,748 cases and 3,444 controls (28% men). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional logistic regression. Results. Compared to those with normal weight (BMI <25 kg/m 2 ), the adjusted overall OR for developing ACPA-negative RA was 1.1 (95% CI 0.9 -1.3) for overweight individuals (BMI >25 to <30 kg/m 2 ) and 1.4 (95% CI 1.1-1.9) for obese individuals (BMI >30 kg/m 2 ). When stratified by sex, the OR for ACPA-negative RA for obese women was 1.6 (95% CI 1.2-2.2), and there was no association between obesity and ACPA-negative RA in men (OR 1.1, 95% CI 0.6 -1.8). In obese men compared to men with normal weight, the OR for ACPA-positive RA was 0.6 (95% CI 0.3-0.9), while there was no association between BMI and ACPA-positive RA among women (OR 1.0, 95% CI 0.8 -1.2). Conclusion. Our findings show that obesity is associated with developing ACPA-negative RA in women, and indicate an inverse association between BMI and ACPA-positive RA in men.

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“…Baseline variables possibly influencing the patient's disease state and MTX response were selected based on the literature (10)(11)(12)(13)(14)(15)(16)(17)(18)20,23,27,28). The following factors were iden-tified: sex; rheumatoid factor (RF) status; age; duration of joint symptoms; alcohol consumption; smoking; body mass index; menopausal status; hormone supplementation; scores for physician's assessment of disease activity, pain, patient's assessment of disease activity, patient's assessment of global health, and morning stiffness on a 0-100-point VAS; Health Assessment Questionnaire (HAQ) score (29); ESR; C-reactive protein level; DAS; SJC; RAI; kidney function (defined as creatinine clearance); anti-cyclic citrullinated peptide (anti-CCP) status; NSAID use; and the existence of comorbidity based on drug use (other than RA disease-related drugs).…”

Section: Methodsmentioning

confidence: 99%

A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent‐onset rheumatoid arthritis

Wessels

Kooij

Cessie

et al. 2007

Arthritis & Rheumatism

223

152

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Objective. To develop a clinical pharmacogenetic model to predict the efficacy of methotrexate (MTX) in rheumatoid arthritis (RA).Methods. Two hundred five patients with newly diagnosed RA and active disease were treated with MTX (initiated at a dosage of 7.5 mg/week and increased to 15 mg/week after 4 weeks) and folic acid (1 mg/day). If the Disease Activity Score (DAS) was >2.4 at 3 months, the dosage of MTX was increased up to 25 mg/week. Twenty-four baseline variables possibly influencing disease state and drug response were selected. In addition, 17 polymorphisms in 13 genes related to the MTX mechanism of action, purine and pyrimidine synthesis, were determined. Factors were compared between responders (defined as patients with a DAS <2.4 at 6 months) and nonresponders. In case of differences, a stepwise selection procedure identified the predictors for response. A clinical score was designed by simplifying regression coefficients of the independent variables. Cutoff levels were chosen based on the clinical score, and positive and negative response rates were calculated. An evaluation of the model was performed in a second group of patients.Results. The model for MTX efficacy consisted of sex, rheumatoid factor and smoking status, the DAS, and 4 polymorphisms in the AMPD1, ATIC, ITPA, and MTHFD1 genes. This prediction model was transformed into a scoring system ranging from 0 to 11.5. Scores of <3.5 had a true positive response rate of 95%. Scores of >6 had a true negative response rate of 86%. Sixty percent of the patients were categorized as either responders or nonresponders, whereas 32% of the patients were categorized using a nongenetic model. Evaluation of the model in 38 additional patients with RA supported the results.Conclusion. This study established a model for predicting the efficacy of MTX in patients with RA. This pharmacogenetic model may lead to better-tailored initial treatment decisions in patients with RA.

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Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression

Cited by 299 publications

References 21 publications

Alterations of the synovial T cell repertoire in anti–citrullinated protein antibody–positive rheumatoid arthritis

Alterations of the synovial T cell repertoire in anti–citrullinated protein antibody–positive rheumatoid arthritis

Association between body mass index and anti–citrullinated protein antibody–positive and anti–citrullinated protein antibody–negative rheumatoid arthritis: Results from a population‐based case–control study

A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent‐onset rheumatoid arthritis

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