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Objective: Evaluate and correlate data between relevant cytokines, disease progression, and handgrip and quality of life among RA patients at different stages of disease progression. Method: Thirty-three RA patients were recruited for analysis, using comparisons and correlations, between levels of circulating cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, IL-1ß, and TNF receptors I and II), activity of the disease (evaluated using the DAS-28), handgrip (Hydraulic dynamometer), and quality of life (SF-36). Result: RA patients in different disease stages showed increases of IL-6 and IL-10 compared control group. Positive correlation between IL-6 with TNF-α, and IL-4 with IL-10 was found. Handgrip strength and quality of life were not related to cytokine levels. However, remission patients had better strength and quality of life indices compared to the active patients. In addition, handgrip of the non-dominant side, physical functions, role limitations physical health, pain, energy/fatigue and social functions have a negative correlation with the DAS28-PCR. Conclusion: High levels of IL-6 and IL-10 were observed in the chronic RA patients, but the values did not show correlation with disease activity, handgrip strength and quality of life. Disease activity show correlation with handgrip strength and quality of life. Furthermore, remission patients had better strength and quality of life indices compared to the active patients.
Objetivo: Avaliar e correlacionar dados entre citocinas relevantes, progressão da doença, preensão manual e qualidade de vida entre pacientes com AR em diferentes estágios de progressão da doença. Método: Trinta e três pacientes com AR foram recrutados para análise, por meio de comparações e correlações, entre níveis de citocinas circulantes (IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, IL-1ß e receptores de TNF-I e -II), atividade da doença (avaliada pelo DAS-28), preensão manual (dinamômetro hidráulico) e qualidade de vida (SF-36). Resultado: Pacientes com doença ativa e inativa apresentaram aumento de IL-6 e IL-10 comparados ao grupo controle. Foi encontrada correlação positiva entre IL-6 com TNF-α e IL-4 com IL-10. A força de preensão e a qualidade de vida não relacionaram aos níveis de citocinas. Entretanto, pacientes em remissão apresentaram melhores índices de força e qualidade de vida comparados aos pacientes com doença ativa. Além disso, preensão manual do lado não dominante, e quesitos dos SF-36, apresentam correlação negativa com o DAS28-PCR. Conclusão: Foram observados níveis elevados de IL-6 e IL-10 nos pacientes com AR crônica, mas os valores não mostraram correlação com DAS-28, força de preensão manual e SF-36. A atividade da doença apresenta correlação com força de preensão manual e qualidade de vida. Além disso, os pacientes em remissão apresentaram melhores índices de força e qualidade de vida em comparação aos pacientes ativos.
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Humanos , Artritis Reumatoide , Fuerza de la ManoRESUMEN
Rheumatoid Arthritis (RA) is a multifactorial autoimmune disease. Currently, several genes play an important role in the development of the disease. The objective was to evaluate the association of the STAT4 rs7574865 and rs897200 gene variants with RA susceptibility, DAS28, RF, and anti-CCP in Western and Southern Mexico populations. Genotyping was performed on 476 samples (cases = 240; controls = 236) using the Taqman® system and qPCR probes. Disease activity was assessed using DAS28 and HAQ DI. CRP, ESR, RF, and anti-CCP were determined for clinical assessment. Our study showed there is a statistically significant association with susceptibility to RA for the rs7574865 variant in the Western population for the GT and TT genotypes. The same genotypes also showed a moderate-to-high activity according to DAS28 and positive anti-CCP compared to the control group. This association was not found in the Southern population. This work confirms the association of the rs7574865 variant with RA, as well as a moderate-to-high activity and positive anti-CCP in the Western population but not in the Southern population. No association of the rs897200 variant was found in any of the studied populations.
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Anticuerpos Antiproteína Citrulinada , Artritis Reumatoide , Humanos , México , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Artritis Reumatoide/genética , Factor de Transcripción STAT4/genéticaRESUMEN
Few studies analyze the role of B-cell subpopulations in rheumatoid arthritis (RA) pathophysiology. Therefore, this study aimed to analyze the differences in B-cell subpopulations and B-cell activation according to disease activity, RA subtype, and absence of disease-modifying antirheumatic drugs (DMARDs) therapy. These subgroups were compared with control subjects (CS). One hundred and thirty-nine subjects were included, of which 114 were RA patients, and 25 were controls. Patients were divided into 99 with seropositive RA, 6 with seronegative RA, and 9 without DMARDs. The patients with seropositive RA were subclassified based on the DAS28 index. A seven-color multicolor flow cytometry panel was used to identify B-cell immunophenotypes and cell activation markers. There were no changes in total B-cell frequencies between RA patients and controls. However, a lower frequency of memory B cells and pre-plasmablasts was observed in seropositive RA compared to controls (P < 0.0001; P = 0.0043, respectively). In contrast, a higher frequency of mature B cells was observed in RA than in controls (P = 0.0002). Among patients with RA, those with moderate activity had a higher percentage of B cells (P = 0.0021). The CD69+ marker was increased (P < 0.0001) in RA compared to controls, while the CD40+ frequency was decreased in patients (P < 0.0001). Transitional, naïve, and double-negative B-cell subpopulations were higher in seronegative RA than in seropositive (P < 0.01). In conclusion, in seropositive and seronegative RA patients, there are alterations in B-cell activation and B-cell subpopulations, independently of clinical activity and DMARDs therapy.
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Antirreumáticos , Artritis Reumatoide , Humanos , Autoanticuerpos , Artritis Reumatoide/tratamiento farmacológico , Linfocitos B , Antirreumáticos/uso terapéutico , Citometría de FlujoRESUMEN
Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2-4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0-56.0) years old and disease duration of 12.0 (6.0-12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. Conclusion The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.
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Abstract Background Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. Methods We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. Results Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. Conclusion In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.
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B cells, follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are part of a circuit that may play a role in the development or progression of rheumatoid arthritis (RA). With the aim of providing further insight into this topic, here we evaluated the frequency of different subsets of Tfh and Tfr in untreated and long-term treated RA patients from a cohort of Argentina, and their potential association with particular human leukocyte antigen (HLA) class-II variants and disease activity. We observed that the frequency of total Tfh cells as well as of particular Tfh subsets and Tfr cells were increased in seropositive untreated RA patients. Interestingly, when analyzing paired samples, the frequency of Tfh cells was reduced in synovial fluid compared to peripheral blood, while Tfr cells levels were similar in both biological fluids. After treatment, a decrease in the CCR7loPD1hi Tfh subset and an increase in the frequency of Tfr cells was observed in blood. In comparison to healthy donors, seropositive patients with moderate and high disease activity exhibited higher frequency of Tfh cells while seropositive patients with low disease activity presented higher Tfr cell frequency. Finally, we observed that HLA-DRB1*09 presence correlated with higher frequency of Tfh and Tfr cells, while HLA-DRB1*04 was associated with increased Tfr cell frequency. Together, our results increase our knowledge about the dynamics of Tfh and Tfr cell subsets in RA, showing that this is altered after treatment.
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Artritis Reumatoide , Linfocitos T Reguladores , Humanos , Células T Auxiliares Foliculares , Cadenas HLA-DRB1/genética , Linfocitos T Colaboradores-InductoresRESUMEN
Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR. METHODOLOGY: 101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0. RESULTS: According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p <0.05). CONCLUSIONS: The results support the need for further study of the role of sCD74 as a soluble MIF decoy receptor, sequestering it to negatively regulate MIF signaling though its membrane receptors. The expression patterns of CXCR4 and CXCR7 show that the latter is a scavenger-type receptor that prevents endocytosis and even degradation of CXCR4 under inflammatory conditions.
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BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine capable of stimulating inflammatory cytokine and matrix metalloproteinase production from macrophages and synovial fibroblasts, which leads to persistent inflammation and bone degradation, two of the major pathological processes in rheumatoid arthritis (RA). The aim of this study was to evaluate the association of MIF promoter polymorphisms (-794CATT5-8 rs5844572 and -173G > C, rs755622), circulating MIF levels, and mRNA expression with RA susceptibility and disease activity. METHODS: A case-control study was conducted in 200 RA patients and 200 control subjects (CS) from Southern Mexico. Genotyping was performed by conventional PCR and PCR-RFLP methods. MIF mRNA expression was quantified by real-time PCR and MIF serum levels were determined by an ELISA kit. RESULTS: The 7,7 (-794CATT5-8 ) and -173CC (-173G > C) genotypes were associated with higher disease activity in RA patients. MIF serum levels were increased, and MIF mRNA expression was reduced in RA patients as compared to CS. In addition, RA patients with moderate disease activity had higher MIF levels than those with low disease activity. The -794CATT5-8 and -173G > C MIF polymorphisms were not associated with RA susceptibility. CONCLUSION: These results suggest an important role of MIF polymorphisms and MIF serum levels with disease activity in RA.
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Artritis Reumatoide/genética , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Artritis Reumatoide/patología , Femenino , Humanos , Oxidorreductasas Intramoleculares/sangre , Oxidorreductasas Intramoleculares/metabolismo , Factores Inhibidores de la Migración de Macrófagos/sangre , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Masculino , México , Persona de Mediana Edad , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
We performed this study to measure the Tumor Necrosis Factor-alpha (TNF-α) plasma level and to survey its correlation with disease activity in the newly diagnosed Rheumatoid Arthritis (RA) patients and those who were under treatment with the combination of Disease-Modifying Anti-Rheumatic Drug (DMARD) plus Prednisolone (PSL).We enrolled 30 newly diagnosed RA patients who received no treatment regarding their disease, 30 patients under treatment with the combination of Methotrexate (MTX) + Hydroxychloroquine (HCQ) + PSL and 30 healthy subjects in this case-control study from September 2017 to December 2017. The level of plasma TNF-α was measured by enzyme-linked immunosorbent assay (ELISA) in each group. For assessment of disease severity, we used Disease Activity Score-28 (DAS-28) formula, and regarding DAS-28, we divided patients into four groups, including remission, low, moderate and high disease activity. There were no significant differences in the plasma level of TNF-α between the newly diagnosed RA patients and subjects who received MTX + HCQ + PSL, as well as healthy controls (p>0.05). There was a significant correlation between plasma levels of TNF-α and DAS-28 in the newly diagnosed patients with RA (r = 0.594, P = 0.001). Targeting TNF-α at the early stage of RA could have more beneficial effects on the amelioration of disease activity
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Pacientes/clasificación , Artritis Reumatoide/patología , Linfotoxina-alfa/farmacología , Antirreumáticos/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Factor de Necrosis Tumoral alfa/farmacología , AntirreumáticosRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) and periodontal disease are inter-related conditions. However, factors predictive of periodontal disease progression in patients with early rheumatoid arthritis (eRA) are lacking. The aim of this study was to identify factors associated with the progression of clinical attachment loss (CAL) in interproximal dental sites of eRA patients. METHODS: Twenty-eight eRA patients were evaluated for the progression of CAL at 280 interproximal dental sites at 1 year of follow-up. Markers of RA activity (rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein), a marker of bone resorption (Dickkopf-related protein 1), Disease Activity Score 28 and Simple Disease Activity Index were included as potential systemic predictive factors. Plaque index, gingival index, pocket depth, clinical attachment level and Dickkopf-related protein 1 in crevicular fluid at baseline were included as potential local predictive factors. Data were analysed in a hierarchical structure using generalised linear mixed models for progression at each site (> 2 mm) during follow-up. RESULTS: C-reactive protein level was the most important predictive systemic factor for the progression of CAL. The mean CAL and a high degree of gingival inflammation in interproximal sites at baseline were important predictive local factors (p < 0.0001). Patients who received combined treatment with disease-modifying antirheumatic drugs and corticosteroids exhibited less CAL (p < 0.0001). The predictive value of the generalised linear mixed model for progression was 85%. CONCLUSIONS: Systemic factors, including RA disease activity and baseline periodontal condition, were associated with periodontal progression. Pharmacological treatment may affect periodontal progression in patients with early RA.
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Antirreumáticos , Artritis Reumatoide , Enfermedades Periodontales , Antirreumáticos/uso terapéutico , Artritis Reumatoide/complicaciones , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Pérdida de la Inserción Periodontal , Enfermedades Periodontales/complicacionesRESUMEN
BACKGROUND: Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA). It has recently been reported that in addition to T helper (Th) 17 cells, other cells, including neutrophils, produce IL-17A, an important inflammatory cytokine involved in the pathogenesis of RA. The purpose of this study was to examine the presence of interleukin 17A-producing neutrophils in patients with RA. METHODS: We performed a cross-sectional study including 106 patients with RA and 56 healthy individuals. Whole peripheral blood cells were analyzed by flow cytometry to identify CD66b+ CD177+ IL-17A+ neutrophils and CD3+ CD4+ IL-17A+ T cells. Serum levels of IL-17A and IL-6 were measured by means of cytometry bead array (CBA). In purified neutrophils, mRNA levels of IL-17 and RORγ were measured by RT-PCR. In addition, purified neutrophils from patients and healthy controls were stimulated with the cytokines IL-6 and IL-23 to evaluate differences in their capacity to produce IL-17A. RESULTS: Neutrophils from RA patients expressed IL-17 and RORγ mRNA. Consequently, these cells also expressed IL-17A. Serum IL-17A levels but not Th17 cell numbers were increased in RA patients. Neutrophils positive for cytoplasmic IL-17A were more abundant in patients with RA (mean 1.2 ± 3.18%) than in healthy individuals (mean 0.07 ± 0.1%) (p < 0.0001). Although increased IL-17A+ neutrophil numbers were present in RA patients regardless of disease activity (mean 6.5 ± 5.14%), they were more frequent in patients with a more recent diagnosis (mean time after disease onset 3.5 ± 4.24 years). IL-6 and IL-23 induced the expression of RORγ but failed to induce IL-17A expression by neutrophils from RA patients and healthy individuals after a 3 h stimulation. CONCLUSION: IL-17A-producing neutrophils are increased in some RA patients, which are not related to disease activity but have an increased frequency in patients with recent-onset disease. This finding suggests that IL-17A-producing neutrophils play an early role in the development of RA.
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The predominance of the effector mechanisms by CD4 + T cells is a characteristic of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). The CD40/CD40L costimulatory pathway contributes to these pathogenic mechanisms by promoting autoantibody production and inflammation. Aberrant expression of CD40 and CD40L in RA patients has been shown, the latter prevailing in females. However, contrasting results have emerged regarding the clinical associations of these findings. We determined the association of CD40 and CD40L expression with the clinical activity evaluated through DAS28 in RA patients. A total of 38 female RA patients and 10 age- and sex-matched control subjects were included. CD40 and CD40L mRNA expression was quantified by real-time qPCR, cell surface proteins were determined by flow cytometry, and protein soluble forms were determined by ELISA. The expansion of a CD4 + T cell subpopulation expressing CD40 was identified in the RA group. In addition, high frequencies of CD4 + CD40L + T cells expressing high levels of CD40L, increased levels of sCD40L and overexpression of CD40L mRNA were observed in these patients. Moreover, there was a gradual increase in CD40L when data were stratified according to DAS28, except for very active patients. No correlation was observed between the levels of mRNA, cell surface protein and soluble protein of CD40 and CD40L with the clinical features of RA patients. There is an altered expression of CD40L in female RA patients in association with clinical activity assessed by DAS28, these findings support the evidence that suggests CD40L as a marker of clinical activity.
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Artritis Reumatoide/inmunología , Antígenos CD40/genética , Antígenos CD40/metabolismo , Ligando de CD40/genética , Ligando de CD40/metabolismo , Adulto , Artritis Reumatoide/genética , Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Regulación hacia ArribaRESUMEN
Abstract Objectives: The cross-sectional study aimed to assess left ventricular systolic function using global longitudinal strain (GLS) by speckle-tracking echocardiography (STE) and arterial stiffness using cardio-ankle vascular index (CAVI) in Thai adults with rheumatoid arthritis (RA) and no clinical evidence of cardiovascular disease (CVD). Methods: Confirmed RA patients were selected from a list of outpatient attendees if they were 18 years (y) without clinical, ECG and echocardiographic evidence of CVD, diabetes mellitus, chronic kidney disease, and excess alcoholic intake. Controls were matched with age and sex to a list of healthy individuals with normal echocardiograms. All underwent STE and CAVI. Results: 60 RA patients (females = 55) were analysed. Mean standard deviation of patient and control ages were 50 ± 10.2 and 51 ±9.9 y, respectively, and mean duration of RA was 9.0 ± 6.8 y. Mean DAS28-CRP and DAS28-ESR were 2.9 ± 0.9 and 3.4 ± 0.9, respectively. There was no between-group differences in left ventricular ejection fraction (LVEF), LV sizes, LVMI, LV diastolic function and CAVI were within normal limits but all GLSs values was significantly lower in patients vs. controls: 17.6 ± 3.4 vs 20.4 ± 2.2 (p = 0.03). Multivariate regression analysis demonstrated significant correlations between GLSs and RA duration (p = 0.02), and GLSs and DAS28-CRP (p = 0.041). Conclusions: Patients with RA and no clinical CV disease have reduced LV systolic function as shown by lower GLSs. It is common and associated with disease activity and RA disease duration. 2D speckle-tracking GLSs is robust in detecting this subclinical LV systolic dysfunction.
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Femenino , Humanos , Masculino , Persona de Mediana Edad , Artritis Reumatoide/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Artritis Reumatoide/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Ecocardiografía/métodos , Enfermedades Cardiovasculares , Estudios Transversales , Análisis de Regresión , Reproducibilidad de los Resultados , Diagnóstico por Computador/métodos , Disfunción Ventricular Izquierda/diagnóstico por imagen , Rigidez VascularRESUMEN
AIM: To investigate the relationships of polymorphisms in genes whose protein products are related in the metabolic pathway of folic acid, particularly MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C, and disease activity in Mexican patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). MATERIALS AND METHODS: Sixty-eight patients with RA were included in the study who were being treated with MTX, either with or without other drugs. In addition to general data, disease activity was measured by the disease activity score 28 (DAS28). Single nucleotide polymorphisms (SNPs) genotyping was performed by allelic discrimination using real-time polymerase chain reaction. RESULTS: Differences in genotype (homozygotic or heterozygotic for each allele), allele distributions, and phenotype were not statistically different between the RA group and control populations. We did not find any association between the studied polymorphisms and disease activity nor with the intragroup variables (e.g., clinical activity, body mass index, and single- or combined-drug treatment) or between genetic markers; we also did not find any association within the RA group or between the RA group and control populations. CONCLUSION: Additional studies of more polymorphisms related to this or other metabolic pathways are required to determine the influence of genetics on disease activity in RA.
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Artritis Reumatoide/genética , Ferredoxina-NADP Reductasa/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Proteína de Replicación C/genética , Adulto , Anciano , Alelos , Etnicidad/genética , Femenino , Ferredoxina-NADP Reductasa/metabolismo , Ácido Fólico/genética , Ácido Fólico/metabolismo , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino , Metotrexato , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , México , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Proteína de Replicación C/metabolismoRESUMEN
OBJECTIVE: Rheumatoid arthritis (RA) is a systemic and autoimmune disorder whose primary characteristic is the chronic inflammation of joints. The objective of this study was to evaluate whether there was an association between nuclear factor kappa beta1/IKK epsilon (NF-κB1/IKKε) gene expression and clinical activity in RA. METHODS: Sixty patients with RA were included in the study: 30 with clinical activity and 30 with clinical remission. NF-κB1/IKKε gene expression was performed by real-time quantitative polymerase chain reaction through relative quantification with Taqman probes. A ROC curve for NF-κB1 and IKKε was also constructed. RESULTS: There were significant differences in NF-κB1 and IKKε gene expression (P ≤ .001 and P ≤ .029, respectively) between RA patients with clinical activity and clinical remission. The multivariate lineal general model showed that the use of nonsteroidal anti-inflammatory drugs influenced the NF-κB1 (P = .046) and IKKε (P = .005) expression. The ROC curves for the event "clinical activity" showed the greater area under the curve for NF-κB1 (0.827, 95% CI 0.717-0.937), P ≤ .001. CONCLUSION: Although the use of NSAIDs influences the NF-κB1/IKKε pathway, the IKKε expression might be a useful laboratorial analysis to evaluate the RA clinical activity.
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Artritis Reumatoide/metabolismo , Quinasa I-kappa B/metabolismo , Subunidad p50 de NF-kappa B/metabolismo , Adulto , Artritis Reumatoide/epidemiología , Artritis Reumatoide/genética , Estudios Transversales , Femenino , Humanos , Quinasa I-kappa B/sangre , Quinasa I-kappa B/genética , Linfocitos/química , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Subunidad p50 de NF-kappa B/sangre , Subunidad p50 de NF-kappa B/genética , Curva ROC , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Evaluation of the correlation between disease activity and joint involvement was assessed by MRI in the clinically dominant foot of patients with RA. We conducted a cross-sectional descriptive study of 55 patients with RA, who were subjected to clinical evaluation and MRI assessment. Imaging of the clinically dominant foot was performed, and both the Disease Activity Score 28 (DAS28-CRP) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) were measured. The majority of patients classified as in clinical remission presented some degree of inflammatory activity upon MRI evaluation. Statistical analysis demonstrated no correlation between MRI findings and clinical scores. There is evidence of disease activity on MRI of the clinically dominant foot even in patients classified as in clinical remission according to the DAS28-CRP criteria.
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Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/patología , Articulaciones del Pie/diagnóstico por imagen , Imagen por Resonancia Magnética , Sinovitis/diagnóstico por imagen , Sinovitis/patología , Adulto , Anciano , Estudios Transversales , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Físico , Inducción de Remisión , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
The objective of this study is to correlate the patient-driven tool Routine Assessment of Patient Index Data 3 (RAPID-3) with other common tools used in daily practice to measure disease activity in rheumatoid arthritis (RA).One hundred nineteen RA patients according to 1987 American College of Rheumatology criteria who consecutively attended a RA outpatient clinic between August and December 2015 were evaluated. Data was stored in an electronic form that included demographic information, comorbidities, concomitant medication, and laboratory results. The disease activity was determined by tender and swollen joint count, pain and disease activity visual analog scales (VAS), disease activity score 28 (DAS28), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and multidimensional health assessment questionnaire (MDHAQ). Correlations between RAPID-3 and other disease activity tools were assessed. Mean age was 61 ± 13.8 years with a median disease duration of 14 years (IQR 5-21), 77% were females. Median scores were MDHAQ 0.5 (IQR 0.1-1.2), DAS 28 3.8 (IQR 2.7-5.1), and RAPID-3 12.3 (IQR 6-19). A strong correlation was obtained between RAPID-3 and DAS 28 (r 0.719, p < 0.001), CDAI (r 0.752, p < 0.001), and SDAI (r 0.758, p < 0.001). RAPID-3 had a high correlation with tools regularly used for disease activity assessment of RA patients in daily practice. The ease of its application favors routine use as it does not require laboratory results and joint counts.
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Artritis Reumatoide/diagnóstico , Evaluación de la Discapacidad , Medición de Riesgo/métodos , Artritis Reumatoide/epidemiología , Artritis Reumatoide/rehabilitación , Colombia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Sistema de Registros , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
La artritis reumatoide (AR) es una enfermedad crónica, inflamatoria, autoinmune y multisistémica, cuyo principal blanco es la membrana sinovial. El manejo adecuado y temprano mejora la evolución y pronóstico de la enfermedad. Objetivo: Evaluar los resultados clínicos y funcionales en pacientes con AR temprana. Metodología: Estudio observacional, con seguimiento longitudinal, de una cohorte de pacientes con AR temprana de menos de 12 meses de evolución, clasificados según los criterios de la Liga Europea Contra el Reumatismo y del Colegio Americano de Reumatología (ACR 2010). Se tuvieron en cuenta los criterios de remisión según la Escala de Actividad de la Enfermedad (DAS28-VSG) y el índice de actividad clínica de la enfermedad. Estado funcional según Cuestionario modificado de Evaluación de la Salud. Resultados: Se analizaron 99 pacientes. La edad promedio de los pacientes fue de 47,8 ± 15,5 años, el 93%(92) eran mujeres. Todos los pacientes fueron tratados con fármacos antirreumáticos modificadores de la enfermedad sintéticos. Durante el seguimiento a los 3 meses se observó una disminución significativa en los puntajes del DAS28y actividad clínica de la enfermedad respecto al valor en la visita basal (p <0,05). No se encontraron diferencias significativas en la evolución de pacientes diagnosticados antes y después de 3 meses desde el inicio de los síntomas (p>0,05). Conclusiones: Se evidencia mejoría sustancial de los pacientes con AR temprana tratados durante el primer año de inicio de los síntomas. El seguimiento continuo y periódico de la patología es una herramienta indispensable para evaluar el progreso de la enfermedad y hacer ajustes en el manejo terapéutico
Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune multisystemic disease that affects the synovial joints. An appropriate and early management improves prognosis and course of the disease. Objective: To evaluate the clinical and functional outcomes of patients with RA. Methodology: Observational study with longitudinal follow up in a cohort of patients with early RA, with less than 12 months of evolution, classified according to the European League Against Rheumatism and American College of Rheumatology (ACR 2010) criteria. Remission criteria were taking into account according to Disease Activity Scale (DAS28-VSG), clinical activity disease index, and functional status according to Modified Health Assessment Questionnaire. Results: The analysis included 99 patients with a mean age of 47.8 + 15.5 years, and of which 92 (93%) were women. All patients were treated with synthetic disease-modifying antirheumatic drugs. At 3 months of follow-up, a significant decrease was observed in DAS28 scores and clinical activity disease index compared to the value at baseline values (p<.05). No significant differences were found between patients diagnosed before and after 3 months from onset of symptoms (p>.05). Conclusions: A substantial improvement was observed in patients with early RA treated during first year from onset symptoms. Continuous and periodic monitoring of the pathology is an indispensable tool for evaluating disease progress and making adjustments in the therapeutic management
Asunto(s)
Humanos , Artritis Reumatoide , Derivación y ConsultaRESUMEN
Resumo Introdução: O Disease Activity Score 28 (DAS28) e versões têm sido usados para medir atividade da artrite reumatoide (AR), mas não existe consenso sobre qual é o melhor. Objetivos: Determinar a correlação entre os índices (DAS28 VHS, DAS28 PCR, SDAI e CDAI) e avaliar a concordância dos estratos de atividade com o uso de diferentes pontos de corte. Métodos: Pacientes com artrite reumatoide foram avaliados transversalmente com coleta de dados para cálculo do DAS28 (VHS e PCR), SDAI e CDAI, com o uso de pontos de cortes diferentes para definição de remissão, atividade leve, moderada e alta. Correlações de Pearson foram calculadas para medidas contínuas e concordância (teste de kappa) para os estratos (remissão, atividade leve, moderada e alta). Resultados: De 111 pacientes incluídos, 108 foram mulheres, média de 55,6 anos, tempo de doença de 11 anos. DAS28 (VHS) foi significantemente maior do que DAS28 (PCR) (4 vs. 3,5; p < 0,001) e os valores permaneceram maiores após estratificação por idade, sexo, tempo doença, fator reumatoide e HAQ. Correlações entre índices variaram de 0,84 a 0,99, com melhor correlação entre SDAI e CDAI. Concordâncias entre estratos de atividade variaram de 46,8% a 95,8%. DAS28 (PCR) com ponto de corte para remissão de 2,3 subestimou atividade da doença em 45,8% quando comparado com DAS28 (VHS). SDAI e CDAI apresentaram concordância de 95,8%. Os quatro índices mostraram associação com tempo de doença e HAQ. Conclusões: Embora os índices de atividade apresentem boa correlação, mostram discrepâncias nos estratos de atividade. Tornam-se necessários mais estudos para definir melhor índice e melhores pontos de corte.
Abstract Introduction: The Disease Activity Score 28 (DAS28) and its versions have been used to measure rheumatoid arthritis activity, but there is no consensus about which one is the best. Objectives: Determine the correlation among indexes (DAS28 ESR, DAS28 CRP, SDAI and CDAI) and evaluate agreement of activity strata using different cut-off points. Methods: Rheumatoid arthritis patients were cross-sectionally evaluated with data collection to calculate the DAS28 (ESR and CRP), SDAI and CDAI, using different cut-offs for defining remission, mild, moderate and high activity. Pearson correlations were calculated for continuous measures and agreement (kappa test) for the strata (remission, mild, moderate and high activity). Results: Of 111 patients included, 108 were women, age 55.6 years, 11-year disease duration. DAS28 (ESR) was significantly higher than DAS28 (CRP) (4.0 vs. 3.5; p < 0.001) and the values remained higher after stratification by age, gender, disease duration, rheumatoid factor and HAQ. Correlations among indexes ranged from 0.84 to 0.99, with better correlation between SDAI and CDAI. Agreements among activity strata ranged from 46.8% to 95.8%. DAS28 (CRP) with cut-off point for the remission of 2.3 underestimated disease activity by 45.8% compared with DAS28 (ESR). SDAI and CDAI showed agreement of 95.8%. The four indexes were associated with disease duration and HAQ. Conclusions: Although the activity indexes show good correlation, they show discrepancies in activity strata, thus requiring more researches to define a better index and better cut-off points.
Asunto(s)
Humanos , Masculino , Femenino , Artritis Reumatoide/fisiopatología , Índice de Severidad de la Enfermedad , Brasil , Estudios Transversales , Persona de Mediana EdadRESUMEN
INTRODUCTION: The Disease Activity Score 28 (DAS28) and its versions have been used to measure rheumatoid arthritis (RA) activity, but there is no consensus about which one is the best. OBJECTIVES: Determine the correlation among indexes (DAS28 ESR, DAS28 CRP, SDAI and CDAI) and evaluate agreement of activity strata using different cutoff points. METHODS: Rheumatoid arthritis patients were cross-sectionally evaluated with data collection to calculate the DAS28 (ESR and CRP), SDAI and CDAI, using different cut-offs for defining remission, mild, moderate and high activity. Pearson correlations were calculated for continuous measures and agreement (kappa test) for the strata (remission, mild, moderate and high activity). RESULTS: Of 111 patients included, 108 were women, age 55.6 years, 11-year disease duration. DAS28 (ESR) was significantly higher than DAS28 (CRP) (4.0 vs. 3.5; p<0.001) and the values remained higher after stratification by age, gender, disease duration, rheumatoid factor and HAQ. Correlations among indexes ranged from 0.84 to 0.99, with better correlation between SDAI and CDAI. Agreements among activity strata ranged from 46.8% to 95.8%. DAS28 (CRP) with cut-off point for the remission of 2.3 underestimated disease activity by 45.8% compared with DAS28 (ESR). SDAI and CDAI showed agreement of 95.8%. The four indexes were associated with disease duration and HAQ. CONCLUSIONS: Although the activity indexes show good correlation, they show discrepancies in activity strata, thus requiring more researches to define a better index and better cutoff points.