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Objectives We sought to identify metabolic changes potentially related to rheumatoid arthritis (RA) pathogenesis occurring in the blood prior to its diagnosis. Methods In a US military biorepository, serum samples collected at two...
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Objectives We sought to identify metabolic changes potentially related to rheumatoid arthritis (RA) pathogenesis occurring in the blood prior to its diagnosis. Methods In a US military biorepository, serum samples collected at two timepoints prior to a diagnosis of RA were identified. These were matched to controls who did not develop RA by subject age, race and time between sample collections and RA diagnosis time to stored serum samples. Relative abundances of 380 metabolites were measured using liquid chromatography-tandem mass spectrometry. We determined whether pre-RA case versus control status predicted metabolite concentration differences and differences over time (trajectories) using linear mixed models, assessing for interactions between time, pre-RA status and metabolite concentrations. We separately examined pre-RA and pre-seropositive RA cases versus matched controls and adjusted for smoking. Multiple comparison adjustment set the false discovery rate to 0.05. Results 291 pre-RA cases (80.8% pre seropositive RA) were matched to 292 controls, all with two serum samples (2.7 +/- 1.6 years; 1.0 +/- 0.9 years before RA/matched date). 52.0% were women; 52.8% were White, 26.8% Black and 20.4% other race. Mean age was 31.2 (+/- 8.1) years at earliest blood draw. Fourteen metabolites had statistically significant trajectory differences among pre-RA subjects versus controls, including sex steroids, amino acid/lipid metabolism and xenobiotics. Results were similar when limited to pre seropositive RA and after adjusting for smoking. Conclusions In this military case-control study, metabolite concentration trajectory differences in pre-RA cases versus controls implicated steroidogenesis, lipid/amino acid metabolism and xenobiotics in RA pathogenesis. Metabolites may have potential as biomarkers and/or therapeutic targets preceding RA diagnosis.
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In rheumatoid arthritis (RA), chronic inflammation can enhance the development of sarcopenia with a depletion of muscle mass, strength and performance. Currently, a consensus definition for sarcopenia and solid results for the pre...
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In rheumatoid arthritis (RA), chronic inflammation can enhance the development of sarcopenia with a depletion of muscle mass, strength and performance. Currently, a consensus definition for sarcopenia and solid results for the prevalence of sarcopenia in patients with RA are lacking.In this cross-sectional study, 289 patients ≥18 years with RA were recruited. Dual X-ray absorptiometry was performed to measure appendicular lean mass. Assessment of muscle function included grip strength, gait speed and chair rise time. Prevalence of sarcopenia was defined using the updated European Working Group on Sarcopenia in Older People (EWGSOP2) and the Foundation for the National Institutes of Health (FNIH) definition. In addition, the RA study population was compared with existing data of healthy controls (n=280).4.5% of patients (59.4±11.3 years) and 0.4% of controls (62.9±11.9 years) were affected by sarcopenia according to the EWGSOP2 definition. Body weight (OR 0.92, 95% CI 0.86 to 0.97), body mass index (BMI) (OR 0.70, 95% CI 0.57 to 0.87), C reactive protein (CRP) (OR 1.05, 95% CI 1.01 to 1.10), disease duration (OR 1.08, 95% CI 1.02 to 1.36), current medication with glucocorticoids (OR 5.25, 95% CI 2.14 to 24.18), cumulative dose of prednisone equivalent (OR 1.04, 95% CI 1.02 to 1.05) and Health Assessment Questionnaire (HAQ) (OR 2.50, 95% CI 1.27 to 4.86) were associated with sarcopenia in patients with RA. In contrast, the prevalence was 2.8% in patients compared with 0.7% in controls when applying the FNIH definition, and body height (OR 0.75, 95% CI 0.64 to 0.88), BMI (OR 1.20, 95% CI 1.02 to 1.41), CRP (OR 1.06, 95% CI 1.01 to 1.11) and HAQ (OR 2.77, 95% CI 1.17 to 6.59) were associated with sarcopenia.Sarcopenia is significantly more common in patients with RA compared with controls using the EWGSOP2 criteria. The FNIH definition revealed sarcopenia in individuals with high BMI and fat mass, regardless of the presence of RA.It was registered at the German Clinical Trials Registry (DRKS) as well as WHO Clinical Trials Registry (ICTRP) (DRKS00011873, registered on 16 March 2017).
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The mutilans type of rheumatoid arthritis (RA)is refractory to several treatments and involves many types of surgical application. It is difficult to prevent its progress, and it has a poor functional prognosis. However, the defin...
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The mutilans type of rheumatoid arthritis (RA)is refractory to several treatments and involves many types of surgical application. It is difficult to prevent its progress, and it has a poor functional prognosis. However, the definition is not always distinct. In this report, I attempt to clarify the clinical features of the mutilans type of RA and establish an accurate definition of the disease. Previous definitions have been divided into three groups: (1) the mutilans group (Mu-G), which has more than three joints showing severe resorptive bone destruction and joint instability; (2) the suspected mutilans group (sMu-G) which has one to two joints with joint instability or showing no instability but with highly resorptive bone destruction; (3) the Larsen V group (LV-G), which has radiological findings indicating Larsen grade V disease. Patients suffering from rheumatoid arthritis for over 10 years and who do not fall into any of the above groups are referred to as the control group. Among 337 patients who suffered from RA for more than 10 years, 58 were classified as being in the mutilans group, 59 in the suspected Mu-G, 47 in the LV-G, and 173 in the control group. The mutilans group had distinctive features which were different from those of the other groups, which had a radiological finding of Larsen grade V disease or severe resorptive bone destruction without instability. From these data, the definition of the mutilans type of RA should be specified as the Mu-G. Thus, the Mu-G shows a distinctive clinical picture which is unlike that in the other groups. It is important to define the mutilans type of RA clearly because it has a poor prognosis. Early identification will help in the establishment of a treatment plan.
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In den Jahren 1985–1993 wurden 120 Ellenbogengelenke bei 106 Patienten offen synovektomiert. Retrospektiv konnten 2 Patientengruppen nachuntersucht werden. Die 1. Gruppe umfasst die offene Synovektomie mit Erhalt des Radiusköpfc...
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In den Jahren 1985–1993 wurden 120 Ellenbogengelenke bei 106 Patienten offen synovektomiert. Retrospektiv konnten 2 Patientengruppen nachuntersucht werden. Die 1. Gruppe umfasst die offene Synovektomie mit Erhalt des Radiusköpfchens (36 Patienten mit 38 Gelenken); 28 Patienten konnten nach durchschnittlich 8,2 Jahren klinisch und radiologisch nachuntersucht werden. Im 2. Kollektiv der Spätsynovektomien mit Radiusköpfchenresektion wurden 70 Patienten (82 Gelenke) operiert. Nachuntersucht werden konnten 50 Patienten mit einem durchschnittlichen Beobachtungszeitraum von 9,3 Jahren.
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The hand and wrist are among the most common anatomical areas involved in rheumatic diseases, especially seropositive and seronegative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The purpose of this study was to ident...
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The hand and wrist are among the most common anatomical areas involved in rheumatic diseases, especially seropositive and seronegative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The purpose of this study was to identify the most differentiating radiographic characteristics of PsA, seropositive RA, and seronegative RA, particularly in the early stages. A retrospective analysis of radiographic hand findings was performed on 180 seropositive RA patients (29 males, 151 females, mean age at the point of acquisition of the analyzed radiograph of 53.4 y/o, SD 12.6), 154 PsA patients (45 males, 109 females, age median of 48.1 y/o, SD 12.4), and 36 seronegative RA patients (4 males, 32 females, age median of 53.1 y/o, SD 17.1) acquired during the period 2005–2020. Posterior–anterior and N?rgaard views were analyzed in all patients. The radiographs were evaluated for three radiographic findings: type of symmetry (asymmetric/bilateral/changes in corresponding joint compartments/‘mirror-image’ symmetry), anatomic location (e.g., wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP) joints), and type of lesions (e.g., juxta-articular osteoporosis, bone cysts, erosions, proliferative bone changes). The study showed that symmetric distribution of lesions defined as ‘lesions present in corresponding compartments’ was more suggestive of seropositive or seronegative RA than PsA. Lesions affecting the PIP joints, wrist, or styloid process of the radius; juxta-articular osteoporosis, joint space narrowing, joint subluxations, or dislocations were more common in patients with seropositive RA than in those with PsA, whereas DIP joints’ involvement and proliferative bone changes were more likely to suggest PsA than seropositive RA. Lesions in PIP, MCP, and wrist joints, as well as erosions, advanced bone damage, joint subluxations, dislocations, and joint space narrowing, were more common in seropositive RA patients than in seronegative RA patients. The ulnar styloid was more commonly affected in seronegative RA patients than in PsA patients. The study confirmed that types of bone lesions and their distribution in the hands and wrists can be useful in differentiating seropositive RA from PsA and suggests that seronegative RA varies in radiological presentation from seropositive RA and PsA.
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The adaptive immune response in rheumatoid arthritis (RA) is influenced by an interaction between host genetics and environment, particularly the host microbiome. Association of the gut microbiota with various diseases has been re...
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The adaptive immune response in rheumatoid arthritis (RA) is influenced by an interaction between host genetics and environment, particularly the host microbiome. Association of the gut microbiota with various diseases has been reported, though the specific components of the microbiota that affect the host response leading to disease remain unknown. However, there is limited information on the role of gut microbiota in RA. In this study we aimed to define a microbial and metabolite profile that could predict disease status. In addition, we aimed to generate a humanized model of arthritis to confirm the RA-associated microbe. To identify an RA biomarker profile, the 16S ribosomal DNA of fecal samples from RA patients, first-degree relatives (to rule out environment/background as confounding factors), and random healthy non-RA controls were sequenced. Analysis of metabolites and their association with specific taxa was performed to investigate a potential mechanistic link. The role of an RA-associated microbe was confirmed using a human epithelial cell line and a humanized mouse model of arthritis. Patients with RA exhibited decreased gut microbial diversity compared with controls, which correlated with disease duration and autoantibody levels. A taxon-level analysis suggested an expansion of rare taxa, Actinobacteria, with a decrease in abundant taxa in patients with RA compared with controls. Prediction models based on the random forests algorithm suggested that three genera, Collinsella, Eggerthella, and Faecalibacterium, segregated with RA. The abundance of Collinsella correlated strongly with high levels of alpha-aminoadipic acid and asparagine as well as production of the proinflammatory cytokine IL-17A. A role for Collinsella in altering gut permeability and disease severity was confirmed in experimental arthritis. These observations suggest dysbiosis in RA patients resulting from the abundance of certain rare bacterial lineages. A correlation between the intestinal microbiota and metabolic signatures could determine a predictive profile for disease causation and progression.
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The study was conducted to investigate the frequency of three gene polymorphisms in the 3-untranslated region (3-UTR) of human leucocyte antigen-G (HLA-G) gene in south Indian patients with rheumatoid arthritis (RA) and analyze th...
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The study was conducted to investigate the frequency of three gene polymorphisms in the 3-untranslated region (3-UTR) of human leucocyte antigen-G (HLA-G) gene in south Indian patients with rheumatoid arthritis (RA) and analyze their influence on disease susceptibility, phenotype and treatment response. HLA-G 14bp insertion (Ins)/deletion (del) (rs66554220), HLA-G +3142G>C (rs1063320) and +3187A>G (rs9380142) polymorphism was analyzed in 221 RA patients and 200 healthy controls. Frequency of HLA-G genotypes or alleles did not differ between patients and controls. Analysis based on rheumatoid factor (RF) status revealed that the frequency of allele A' (rs9380142) was significantly higher in RF-positive than in RF-negative patients [84% vs 74%, Yates-corrected P value (Pc)=0.04, odds ratio (OR)=1.8, 95% confidence interval (CI)=1.0-3.2]. A similar difference was maintained in RF-positive female patients than their RF-negative counterparts (83% vs 71%, Pc=0.02, OR=1.9, 95% CI=1.0 to 3.4) and between RF-positive and RF-negative young onset RA (YORA) patients (84% vs 73%, Pc=0.03, OR=1.9, 95% CI=1.0-3.2), suggesting that rs9380142 polymorphism influenced RF status. The 14bp Ins allele of rs66554220 was significantly more prevalent in RF-positive YORA than in RF-positive late onset RA (LORA) patients (51% vs 25%, P=0.03, OR=3.1, 95% CI=1.1-9.8). Frequency of the four major haplotypes [InsGA (48%), DelGA (22%), DelCG (18%), DelCA (9.7%)] observed did not differ between cases and controls. HLA-G does not appear to be a risk factor for development of RA in south Indian Tamils but may act as a genetic modifier of clinical phenotype in terms of autoantibody production, gender preference and age at disease onset.
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