Clonal expansion of T cell specificities in the synovial fluid of patients has been taken as evidence for a local stimulation of T cells. By studying the T cell receptor (TCR) repertoire of CD4± T cells in the synovial and peripheral blood compartments of patients with early rheumatoid arthritis (RA), we have identified clonally expanded CD4 + populations. Expanded clonotypes were present in the peripheral blood and the synovial fluid but were not preferentially accumulated in the joint. Dominant single clonotypes could not be isolated from CD4+ cells of HLA-DRB1 *04+ normal individuals. Clonal expansion involved several distinct clonotypes with a preference for Vf633, V1314', and VJ817'CD4+ T cells. A fraction of clonally related T cells expressed IL-2 receptors, indicating recent activation. The frequencies of clonally expanded V/317+CD4+ T cells fluctuated widely over a period of one year. Independent variations in the frequencies of two distinct clonotypes in the same patient indicated that different mechanisms, and not stimulation by a single arthritogenic antigen, were involved in clonal proliferation. These data support the concept that RA patients have a grossly imbalanced TCR repertoire. Clonal expansion may result from intrinsic defects in T cell generation and regulation.The dominance of expanded clonotypes in the periphery emphasizes the systemic nature of RA and suggests that T cell proliferation occurs outside of the joint. (J. Clin. Invest. 1994. 94
Background Timely diagnosis and treatment are essential in the effective management of inflammatory rheumatic diseases (IRDs). Symptom checkers (SCs) promise to accelerate diagnosis, reduce misdiagnoses, and guide patients more effectively through the health care system. Although SCs are increasingly used, there exists little supporting evidence. Objective To assess the diagnostic accuracy, patient-perceived usability, and acceptance of two SCs: (1) Ada and (2) Rheport. Methods Patients newly presenting to a German secondary rheumatology outpatient clinic were randomly assigned in a 1:1 ratio to complete Ada or Rheport and consecutively the respective other SCs in a prospective non-blinded controlled randomized crossover trial. The primary outcome was the accuracy of the SCs regarding the diagnosis of an IRD compared to the physicians’ diagnosis as the gold standard. The secondary outcomes were patient-perceived usability, acceptance, and time to complete the SC. Results In this interim analysis, the first 164 patients who completed the study were analyzed. 32.9% (54/164) of the study subjects were diagnosed with an IRD. Rheport showed a sensitivity of 53.7% and a specificity of 51.8% for IRDs. Ada’s top 1 (D1) and top 5 disease suggestions (D5) showed a sensitivity of 42.6% and 53.7% and a specificity of 63.6% and 54.5% concerning IRDs, respectively. The correct diagnosis of the IRD patients was within the Ada D1 and D5 suggestions in 16.7% (9/54) and 25.9% (14/54), respectively. The median System Usability Scale (SUS) score of Ada and Rheport was 75.0/100 and 77.5/100, respectively. The median completion time for both Ada and Rheport was 7.0 and 8.5 min, respectively. Sixty-four percent and 67.1% would recommend using Ada and Rheport to friends and other patients, respectively. Conclusions While SCs are well accepted among patients, their diagnostic accuracy is limited to date. Trial registration DRKS.de, DRKS00017642. Registered on 23 July 2019
IntroductionThe aim of this study was to evaluate the safety and efficacy of rituximab (RTX) in a large cohort of patients with rheumatoid arthritis in routine care, and to monitor changes in daily practice since the introduction of RTX therapy.MethodsThis was a multicentre, prospective, non-interventional study conducted under routine practice conditions in Germany. Efficacy was evaluated using Disease Activity Score in 28 joints (DAS28) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed by recording adverse drug reactions (ADRs). Physician and patient global efficacy and tolerability assessments were also evaluated.ResultsOverall, 2,484 patients (76.7% female, mean age 56.4 years, mean disease duration 11.7 years) received RTX treatment (22.7% monotherapy). The total observation period was approximately six-years (median follow-up 14.7 months). RTX treatment led to improvements in DAS28 and HAQ-DI that were sustained over multiple courses. DAS28 improvements positively correlated with higher rheumatoid factor levels up to 50 IU/ml. Response and tolerability were rated good/very good by the majority of physicians and patients. Mean treatment intervals were 10.5 and 6.8 months for the first and last 400 enrolled patients, respectively. Infections were the most frequently reported ADRs (9.1%; 11.39/100 patient-years); approximately 1% of patients per course discontinued therapy due to ADRs.ConclusionsProlonged RTX treatment in routine care is associated with good efficacy and tolerability, as measured by conventional parameters and by physicians’ and patients’ global assessments. Rheumatoid factor status served as a distinct and quantitative biomarker of RTX responsiveness. With growing experience, physicians repeated treatments earlier in patients with less severe disease activity.
Background: Antibodies targeting DNA topoisomerase I (ATA) or centromere proteins (ACA) are associated with clinical subsets of patients with systemic sclerosis (SSc). The occurrence of those autoantibodies is considered to be mutually exclusive. Objective: To describe the clinical and immunogenetic data of three patients who are co-expressing both antibodies, and then review previous publications. Methods: Both antibodies were detected by different methods, including indirect immunofluorescence technique, enzyme linked immunosorbent assay, immunodiffusion, and immunoblot. Patients were HLA typed by serological and molecular genetic methods. Data were extracted from published reports for comparison. The search for published studies was through Medline and other database research programmes. Results: During routine laboratory diagnostics over several years three patients with scleroderma and coincidence of ATA and ACA were identified: patient 1 with diffuse SSc, Raynaud's phenomenon, puffy fingers and fingertip necrosis, contractures, and calcinosis; patient 2 with diffuse SSc, Raynaud's phenomenon, oedema of the hands, and interstitial calcinosis of hands, knees, and shoulders, and pulmonary fibrosis; patient 3 with scleroderma of hands, forearms, and face, Raynaud's phenomenon, puffy fingers, finger contractures, fingertip necrosis, and calcinosis. All three patients studied were carriers of HLA alleles known to be associated with these autoantibodies. In serial measurements the concentrations of the two antibodies showed independent or even reverse fluctuations. Screening of 100 patients with ACA for ATA and vice versa disclosed no further patients with coincidence of these antibodies. Twenty eight cases of ACA/ATA coexistence in 5423 patients (0.52%) with SSc or SSc associated symptoms were found in an analysis of published studies. Conclusion: The expression of ATA and ACA is not totally mutually exclusive, but coincidence is rare (<1% of patients with SSc). Patients with both autoantibodies often have diffuse scleroderma and show immunogenetic features of both antibody defined subsets of SSc.
Objective. To characterize the clinical and immunogenetic features of patients with Mi-2 autoantibodies.Methods. Eighteen adult white patients with Mi-2 antibodies were clinically characterized and compared with 41 Mi-%negative dermatomyositis (DM) patients. HLA class I and class I1 typing for DRB alleles was done by microcytotoxicity assay and for DQA and DQB alleles by polymerase chain reaction-based oligotyping.Results. Seventeen of the 18 Mi->positive patients had DM. Symptoms of scleroderma, lung involvement, and arthritis were less common in this group than in the Mi-%negative DM patients; the V-sign rash and nailfold involvement were found more frequently. Mi-2 antibodies were strongly associated with HLA-DR7 (88% versus 24% in healthy controls), HLA-DQA1*0201(86% versus 23%), and DR7 "homozygosity" (31% versus 0%). A tryptophan residue at position 9 of the HLA-DRP chain was present in all Mi-% positive patients (100% versus 62 % ; homozygous in 81% versus i5%).Conclusion. Our results reemphasize the specificity of Mi-2 antibodies for DM, and extend previous reports that Mi-2 antibody production is associated with certain HLA class I1 antigens. We propose m-Trp as a Supported by the Verein zur Forderung der Rheumaforschung bei der Rheumaklinik Aachen e.V. and by the Deutsche Forschungsgemeinschaft (SFB 217).
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