Immunodominant T-cell epitopes of hnRNP-A2 associated with disease activity in patients with rheumatoid arthritis.

The heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2) has been described as an important autoantigen in rheumatoid arthritis (RA) since it is targeted by autoantibodies, autoreactive T cells, and is aberrantly expressed in synovial cells in patients. To identify hnRNP-A2-specific T-cell epitopes possibly associated with pathogenicity, we used an innovative approach. We first scanned 280 overlapping hnRNP-A2 peptides for binding to the RA-associated class II molecules HLA-DR4 and HLA-DR1, leading to a comprehensive selection of binders. The selected peptides were tested in IFN-gamma-specific ELISPOT assay: PBMC from 18% of RA patients showed a significant IFN-gamma response to hnRNP-A2 peptides, 15% to the overlapping sequences 117-133 and/or 120-133, whereas PBMC from healthy individuals tested negative. We measured proliferative responses to these two peptides in another cohort of patients with RA or osteoarthritis: positive responses were found in 28% of RA, but also in 11% of osteoarthritis patients and these responses could be blocked by anti-MHC class II Ab. Remarkably, the presence of 117/120-133-specific T cells was significantly associated with active disease in RA patients, and bone erosion appeared to be more common in T-cell positive patients. These data suggest involvement of hnRNP-A2 specific cellular autoimmune responses in RA pathogenesis.

I have mastered the challenge of living with a chronic disease: life stories of people with rheumatoid arthritis.

Our aim with this study was to explore the narrative life story of individuals diagnosed with rheumatoid arthritis. An open qualitative approach, namely narrative biographic methodology, was applied to include the life context of the participants and to deliberately exclude predefinitions of concepts. Ten people with rheumatoid arthritis who retired early because of the disease participated and were interviewed three times according to a narrative biographic interview style. The biographical data and the interview texts were analyzed both individually and in comparison to each other. Some participants regarded rheumatoid arthritis as a challenge for mastery in their lives, whereas others adapted to the disease and "made the best out of a bad situation." Especially in countries where the medical model predominates in health care, our findings can be used to broaden the current view that some health professionals have toward patients, and stress the importance of patients being self-responsible.

Concepts important to patients with psoriatic arthritis are not adequately covered by standard measures of functioning.

OBJECTIVE: To explore whether the concepts important to patients with psoriatic arthritis (PsA) are covered by self-report instruments assessing functioning. METHODS: We conducted a qualitative focus group study with PsA patients about their problems in daily functioning. Focus groups were tape recorded and transcribed verbatim. The transcribed texts were divided into meaning units, and concepts contained in these meaning units were extracted. Self-report instruments assessing functioning in PsA were identified in a structured literature search. Using the International Classification of Functioning, Disability and Health (ICF) as a common frame of reference, we determined whether each concept identified in the focus groups was covered by each of the instruments. RESULTS: Thirty-one patients participated in 6 focus groups. The following 9 instruments were included in the present analysis: Arthritis Impact Measurement Scale Short Form; Bath Ankylosing Spondylitis Disease Activity Index; Disabilities of the Arm, Shoulder, and Hand Questionnaire; Dermatology Quality of Life Index; Dougados Functional Index; Health Assessment Questionnaire (HAQ); HAQ-S (HAQ adapted for spondylarthropathies); PsA-specific Quality of Life Instrument; and Short Form 36 Health Survey. Of the 54 concepts identified in 590 meaning units in the transcribed data, 19 concepts (35%) were not covered by any of the instruments. Of these, 11 concepts that were linked to the ICF component environmental factors were not covered by any of the instruments, whereas all concepts linked to the ICF component activities and participation were covered by at least 1 of the instruments (but no single instrument covered all concepts). CONCLUSION: The impact of environmental factors, attitudes towards individuals with health problems, and loss of leisure time may represent important aspects addressing participation that are currently not covered in the instruments assessing functioning in PsA.

Aspects of early arthritis. Traditional DMARD therapy: is it sufficient?

There is increasing evidence for beneficial effects of early DMARD (disease-modifying antirheumatic drug) therapy over delayed treatment in patients who present with arthritis of recent onset. However, no universal consensus exists concerning the choice of initial drug or whether single drugs or combinations should be given as initial treatments. Recent studies have focused on the benefits of various strategies in which treatments were tailored to achieve low levels of disease activity, as assessed using validated response criteria. These studies demonstrated superiority of 'aggressive' over 'conventional' approaches. Whether the inclusion of tumour necrosis factor antagonists or other biologic targeted therapies in such strategies confers additional benefits in terms of improved long-term outcomes must be clarified by further studies. Assessment of risks in the individual patient, allowing individual 'tailoring' of the initial treatment, would be desirable.

Early rheumatoid arthritis.

PURPOSE OF REVIEW: This review provides novel and updated information on pathogenesis, referral, and clinical characteristics as well as therapeutic approaches in early rheumatoid arthritis. RECENT FINDINGS: Early referral is important, but new classification criteria for early rheumatoid arthritis need to be elaborated. Predictive markers for rheumatoid arthritis are still confined to autoantibodies; respective algorithms have been presented. Other biomarkers will still have to prove their usefulness. Magnetic resonance imaging and sonography do not appear to sufficiently distinguish between early rheumatoid and nonrheumatoid arthritis. Rheumatoid arthritis has become milder at presentation in recent years. In its very early stages, the cytokine profile reflects T-cell activation and switches to abundant proinflammatory cytokines thereafter. Disease-modifying antirheumatic drugs plus glucocorticoids are highly effective, as is early use of tumor necrosis factor blockers plus methotrexate. Tight control of disease activity and subsequent therapeutic adjustments are highly effective. Disease activity indices that are simple to calculate have been presented and validated. Early intensive therapy may lead to decrease in disability and cost reduction in rheumatoid arthritis. SUMMARY: Understanding of early arthritis is increasing, especially in prognostic and therapeutic respects, and new treatment strategies appear to improve the outcome in patients with early arthritis. Nevertheless, much remains to be studied to better address the issue of early rheumatoid arthritis.

Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states.

OBJECTIVE: Several composite scores are available to assess the activity of rheumatoid arthritis (RA). Criteria for remission and active RA based on these continuous scores are important for use in clinical practice and clinical trials. We aimed to reevaluate or to define such criteria for the Disease Activity Score in 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI). METHODS: We sampled patient profiles from an observational RA database that included clinical and laboratory variables. Thirty-five rheumatology experts classified these profiles into 1 of 4 categories: remission, low, moderate, or high disease activity. Cutoff values were estimated by mapping scores on the DAS28 and SDAI to these ratings, and analyses of agreement (kappa statistics) and a diagnostic testing approach (receiver operating characteristic curves) were used to validate the estimates. The final criteria were validated using 2 observational cohorts (a routine cohort of 767 patients and an inception cohort of 91 patients). RESULTS: Results from the 3 analyses were very similar and were integrated. The criteria for separating remission, low, moderate, and high disease activity based on the SDAI were scores of 3.3, 11, and 26, respectively; those based on the DAS28 were scores of 2.4, 3.6, 5.5, respectively. In the routine cohort, these cutoff values showed substantial agreement (weighed kappa = 0.70) and discriminated between groups of patients with clearly different functional capacities (P < 0.001). In the inception cohort, these cutoff scores differentiated responders (those with a 20% response on the American College of Rheumatology improvement criteria) from nonresponders (P < 0.01), as well as patients with and without radiologic progression (P < 0.05). CONCLUSION: New criteria for levels of RA disease activity were determined and internally validated. These criteria, which are based on current and explicit expert judgment, are valuable in this era of rapidly advancing therapeutic approaches.

Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score.

INTRODUCTION: Frequent assessments of rheumatoid arthritis (RA) disease activity allow timely adaptation of therapy, which is essential in preventing disease progression. However, values of acute phase reactants (APRs) are needed to calculate current composite activity indices, such as the Disease Activity Score (DAS)28, the DAS28-CRP (i.e. the DAS28 using C-reactive protein instead of erythrocyte sedimentation rate) and the Simplified Disease Activity Index (SDAI). We hypothesized that APRs make limited contribution to the SDAI, and that an SDAI-modification eliminating APRs - termed the Clinical Disease Activity Index (CDAI; i.e. the sum of tender and swollen joint counts [28 joints] and patient and physician global assessments [in cm]) - would have comparable validity in clinical cohorts. METHOD: Data sources comprised an observational cohort of 767 RA patients (average disease duration 8.1 +/- 10.6 years), and an independent inception cohort of 106 patients (disease duration 11.5 +/- 12.5 weeks) who were followed prospectively. RESULTS: Our clinically based hypothesis was statistically supported: APRs accounted only for 15% of the DAS28, and for 5% of the SDAI and the DAS28-CRP. In both cohorts the CDAI correlated strongly with DAS28 (R = 0.89-0.90) and comparably to the correlation of SDAI with DAS28 (R = 0.90-0.91). In additional analyses, the CDAI when compared to the SDAI and the DAS28 agreed with a weighted kappa of 0.70 and 0.79, respectively, and comparably to the agreement between DAS28 and DAS28-CRP. All three scores correlated similarly with Health Assessment Questionnaire (HAQ) scores (R = 0.45-0.47). The average changes in all scores were greater in patients with better American College of Rheumatology response (P < 0.0001, analysis of variance; discriminant validity). All scores exhibited similar correlations with radiological progression (construct validity) over 3 years (R = 0.54-0.58; P < 0.0001). CONCLUSION: APRs add little information on top (and independent) of the combination of clinical variables included in the SDAI. A purely clinical score is a valid measure of disease activity and will have its greatest merits in clinical practice rather than research, where APRs are usually always available. The CDAI may facilitate immediate and consistent treatment decisions and help to improve patient outcomes in the longer term.

Validating the International Classification of Functioning, Disability and Health Comprehensive Core Set for Rheumatoid Arthritis from the patient perspective: a qualitative study.

OBJECTIVE: To validate the International Classification of Functioning, Disability and Health (ICF) Comprehensive Core Set for Rheumatoid Arthritis (RA) from the patient perspective. METHODS: Patients with RA were interviewed about their problems in daily functioning. Interviews were tape recorded and transcribed verbatim. Interview texts were divided into meaning units. The concepts contained in these meaning units were linked to the ICF according to 10 established linking rules. Of the transcribed data, 15% were analyzed and linked by a second health professional. The degree of agreement was calculated using the kappa statistic. RESULTS: Twenty-one patients were interviewed. Two hundred twenty different concepts contained in 367 meaning units were identified in the qualitative analysis of the interviews and linked to 109 second-level ICF categories. Of the 76 second-level categories from the ICF RA Core Set, 63 (83%) were also found in the interviews. Twenty-five second-level categories, which are not part of the current ICF RA Core Set, were identified in the interviews. The result of the kappa statistic for agreement was 0.62 (95% boot-strapped confidence interval 0.59-0.66). CONCLUSION: The validity of the ICF RA Core Set was supported by the perspective of individual patients. However, some additional issues raised in this study but not covered in the current ICF RA Core Set need to be investigated.

Very recent onset arthritis--clinical, laboratory, and radiological findings during the first year of disease.

OBJECTIVE: To describe clinical and radiological findings in patients with very early arthritis (< 3 months of symptoms) during one year of observation. METHODS: In an Austrian multicenter setting, patients were eligible if they had nontraumatic swelling or pain in at least one joint and laboratory signs of inflammation [elevated erythrocyte sedimentation rate, C-reactive protein, leukocytosis, or rheumatoid factor (RF)] within the last 3 months. Clinical and laboratory assessments were performed every 3 months. Radiographs of hands and feet were taken at entry and after one year. Treatment decisions were left to the discretion of the participating center. RESULTS: In total, 108 patients included between 1996 and 2000 had followup investigations during at least one year; 61.1% of these patients had rheumatoid arthritis (RA). Over 65% of RA diagnoses were made at the first visit. Lag time to referral was significantly longer in patients with RA than in patients with other inflammatory joint diseases (median 8 vs 4 weeks). Disease modifying antirheumatic drugs were started 19 +/- 10 (mean +/- SD) weeks after symptom onset in patients with RA. Patients with RA improved significantly (by American College of Rheumatology response criteria and the Disease Activity Score 28) during the first year. Erosions were present in 12.8% of RA patients' initial radiographs, compared to 27.6% after one year. Odds ratio to develop new erosions during the first year of RA was 9.7 (95% CI 1.05-89.93) in RF+ patients compared to RF- individuals (p < 0.05). CONCLUSION: When early referral of patients with arthritis is encouraged, RA can be diagnosed and treatment initiated early, with significant clinical response. Moreover, patients with RA tend to be referred later than patients with other inflammatory joint diseases; RA patients at this very early stage have low frequency of joint damage; and RF predicts erosions in the first year.