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Presentación del caso. Se trata de una mujer de 26 años de edad, en seguimiento por la especialidad de reumatología desde los 17 años, cuando consultó con historia de un año de evolución de síndrome poliarticular de grandes y pequeñas articulaciones, aditivo, simétrico acompañado de fatiga, rigidez matutina mayor de una hora. Se reportó además factor reumatoide positivo. La radiografía de ambas manos presentó erosiones, que confirmó el diagnóstico de artritis reumatoide. Adicionalmente, la paciente tenía el antecedente de procesos sinobronquiales a repetición desde su infancia. En la evaluación médica se identificó dolor en los senos paranasales, dextrocardia y bronquiectasias, confirmados por los estudios de imágenes, que permitió concluir en el diagnóstico de síndrome de Kartagener. Intervención terapéutica. La paciente presentaba actividad clínica severa de la artritis reumatoide, se inició el tratamiento con metotrexato 10 mg vía oral un día a la semana, prednisona 5 mg al día y ácido fólico 5 mg a la semana y citas periódicas, controlando los datos de actividad y efectos adversos de los medicamentos, con pruebas hepáticas, hemograma y transaminasas. La especialidad de neumología recomendó la inclusión de la paciente en un programa de rehabilitación respiratoria, así como el uso de azitromicina 500 mg cada día por tres días en los períodos de agudización. Evolución clínica. El tratamiento logró mantener una actividad leve de la artritis reumatoide y sin exacerbación de los síntomas respiratorios
Case presentation. A 26-year-old woman, under follow-up by the rheumatology specialty since she was 17 years old, when she consulted with a history of one year of evolution of polyarticular disease of large and small joints, additive, symmetrical, accompanied by fatigue and morning stiffness for more than one hour. Positive rheumatoid factor was also reported. Additionally, the patient had a history of repeated sinobronchial processes since childhood. Medical examination revealed sinus pain in the paranasal sinuses, dextrocardia, and bronchiectasis, confirmed by imaging studies, which led to the diagnosis of Kartagener's syndrome. Treatment. The patient presented the severe clinical activity of rheumatoid arthritis. The treatment was started with methotrexate 10 mg orally one day a week, prednisone 5 mg a day, and folic acid 5 mg a week and periodic appointments, controlling the activity data and adverse effects of the drugs, with liver tests, hemogram, and transaminases. The pneumology department recommended the inclusion of the patient in a respiratory rehabilitation program as well as the use of azithromycin 500 mg every day for three days during periods of exacerbation. Outcome. The treatment was successful in maintaining a mild activity of the rheumatoid arthritis and without exacerbation of respiratory symptoms
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Humans , Female , Adult , El SalvadorABSTRACT
Objective To explore the correlation of serum Chemerin level with disease activity and the ratio of T helper 17/regulatory T cells(Th17/Treg)in patients with rheumatoid arthritis(RA).Methods A total of 180 patients with RA who were admitted to our hospital were regarded as the observation group.According to the DAS28 score,the observation group was divided into the high activity group(60 cases),the moderate activity group(60 cases)and the low activity group(60 cases).Another 180 healthy people who underwent physical examination in our hospital during the same period were regarded as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of Chemerin,interleukin-9(IL-9),interleukin-10(IL-10)and interleukin-17(IL-17).Flow cytometry was used to detect the Th17/Treg ratio.Spearman correlation analysis was applied to analyze the correlation between serum Chemerin level and DAS28 score.Pearson correlation analysis was used to analyze the correlation between serum Chemerin level and Th17,Treg cell percentage and Th17/Treg ratio.Results The results of this study showed that the serum level of Chemerin was higher in the observation group than that in the control group(P<0.05).The serum Chemerin level was positively correlated with DAS28 score(P<0.05).Serum Chemerin levels and DAS28 scores decreased in turn in the high,moderate and low activity groups(P<0.05).The percentage of Th17 cells and the ratio of Th17/Treg were higher in the observation group than those in the control group,and the percentage of Treg cells was lower in the observation group than that in the control group(P<0.05).The level of IL-10 was lower in the observation group than that in the control group,while levels of IL-17 and IL-9 were higher in the observation group than those in the control group(P<0.05).The results of Pearson correlation analysis showed that serum Chemerin level was positively correlated with the percentage of Th17 cells and the ratio of Th17/Treg,and negatively correlated with the percentage of Treg cells(P<0.05).Conclusion Serum Chemerin level is elevated in patients with RA,which is closely related to disease activity and Th17/Treg ratio.
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Purpose To assess the right atrial and right ventricular strain and right ventricular-pulmonary artery(RV-PA)coupling in rheumatoid arthritis(RA)via two-dimensional speckle tracking.Materials and Methods Sixty patients with RA in the General Hospital of Ningxia Medical University from June 2020 to June 2022 were prospectively selected,and all RA patients were divided into three groups according to pulmonary artery systolic pressure(PASP),including group A(n=20 cases)with PASP<33 mmHg,group B(n=20 cases)with PASP 33-39 mmHg as mild ePH,and group C(n=20 cases)PASP≥40 mmHg,twenty healthy individuals were selected as the control group.All subjects underwent transthoracic echocardiography,and right atrial and right ventricular systolic function was assessed by two-dimensional speckle tracking technique,and RV-PA coupling was assessed noninvasively by right ventricular free wall strain/pulmonary artery systolic pressure(RV FWS/PASP),pulmonary function was analyzed by pulmonary function instruments.Spearman's analysis was used to analyze the correlation between right heart function and RV-PA coupling to pulmonary diffusion function.Results There were statistical differences in right ventricular base diameter,right atrium diameter,tricuspid annular plane systolic excursion,inferior vena cava diameter,PASP,right ventricular global strain,RV FWS,right atrium strain-reservoi,right atrium strain-conduit(S-CD),RV FWS/PASP among the four groups(F/H=2.369-74.880,all P<0.05).Right atrium strain-reservoi[(36.0±7.9)%vs.(30.9±7.8)%],right atrium S-CD[(19.9±6.9)%vs.(15.3±4.7)%]and RV FWS/PASP(0.96±0.19 vs.0.56±0.13)in group B were significantly lower than those of group A(t=2.040,2.262,7.704,all P<0.05).There was a good correlation between diffusing capacity of the lung for carbon monoxide single-breathmethod and right ventricular global strain,RV FWS,right atrium S-CD and RV FWS/PASP in RA patients(r=0.392,0.472,0.431,0.572,all P<0.05).Conclusion The more increases of pulmonary artery pressures,the more decreases of right heart function in RA patients,and the more uncoupling in RV-PA.Right heart dysfunction and right ventricle-pulmonary artery uncoupling have developed in RA patients with PASP 33-39 mmHg,with association of pulmonary diffusion dysfunction.
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Objective:To compare the efficiency and purity of exosomes extracted from synovial fibroblasts of patients with rheumatoid arthritis by ultracentrifugation, size exclusion chromatography and modified polymer precipitation.Methods:The exosomes were extracted from human synovial fibroblasts by ultracentrifugation, size exclusion chromatography and modified polymer precipitation. Transmission electron microscopy, particle size detection and western Blot were used to identify the morphological characteristics, particle size distribution, concentration, and expression of marker proteins. One-way analysis of variance (ANOVA) was used for comparison among the three groups, and LSD- t test was used for pairwise comparison. P<0.05 was considered statistically significant. Results:Exosomes could be successfully obtained with all three extraction methods. The typical "saucer-like" structure could be observed under transmission electron microscope. The marker proteins of exosomes TSG101, Syntenin-1 and CD63 were all detectable by western blot. The peaks of main particle size were located within 30~150 nm. As for purity, the exosomes obtained by ultracentrifugation showed the highest purity, while modified polymer precipitation was the worst, with a large number of polymer particles and impurities protein. The purity of exosomes obtained by size exclusion chromatography was the moderate. For extraction efficiency, concentrations of exosomes particles obtained by the three methods were different ( F=9.61, P=0.049), and modified polymer precipitation was significantly higher than ultracentrifugation in terms of concentration of exosomes particles [(98.0±17.0)×10 10 particles/ml vs (11.6±7.7)×10 10 particles/ml, t=-4.34, P=0.023]. Conclusion:Human synovial fibroblasts derived exosomes canbe obtained by three methods. Ultracentrifugation is time-consuming, but can produce high-purity exosomes, which may be considered in the situation when high purity requirement with large volume samples are needed. Size exclusion chromatography is a good choice with high yield and purity exosomes, and suitable for small volume samples. Modified polymer precipitation is not recommended due to production of lowest purity exosomes.
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Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.
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Objective:To evaluate the relationship between gluten-free diet and rheumatoid arthritis (RA).Methods:Data were obtained from large-scale genome-wide association studies (GWAS), and genetic loci that are independent of gluten-free diet and RA of people of Europe2 were selected as instrumental variables. The gluten-free diet GWAS data included 64 949 individuals and 9 851 867 controls. Data were obtained from GWAS of 58 284 RA patients and 13 108 512 controls. The inverse variance weighted (IVW), MR Egger, weighted median method and weighted model were used to conduct two sample Mendelian randomization (MR) analysis. Cochran Q test and mendelian randomness pleiotropy residual sum and outlier (MR-PRESSO) were used to assess SNP heterogeneity. Applying the MR Egger intercept to test the level pleiotropy of SNP. The sensitivity analysis of the "leave one method" that evaluates whether MR studies were influenced by a single SNP. Results:After matching GFD and RA data, three SNPs were included as instrumental variables in the study. IVW showed that GFD could significantly reduce the risk of RA ( β=-60.83, s x=3.82, P<0.001). The weighted median method and weighted pattern also showed that the gluten free diet could reduce the risk of RA ( β=-57.97, s x=4.41, P<0.001; β=-55.81, s x=5.10, P=0.008). Sensitivity analysis of the correlation between GFD and RA showed that there might be heterogeneity between SNPs (Cochran Q test, Q=12.80, P=0.002). The MR-PRESSO results showed that no abnormal SNP was detected ( P=0.174). The forest map showed that SNPs was closely related to GFD and RA stability. The method comparison chart showed that the results of multiple testing methods were basically consistent. The funnel plot showed that SNPs were basically symmetrical, indicating that there was no pleiotropy in MR analysis. The MR Egger intercept test showed no horizontal pleiotropy in MR analysis (intercept value was-0.24, P=0.174). The sensitivity analysis of the "leave one method" is suggested that no single SNP had a significant impact on the overall results. Conclusion:Gluten free diet is related to the risk reduction of RA.
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Objective:Screening factors that might influence rheumatoid arthritis (RA) complicating interstitial lung diseases (ILD) by constructing and validating a model for early diagnostic.Methods:The study subjects were composed of 712 RA patients in the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University during December 2019 to October 2022. Fifty-two variables such as their demographic data, clinical symptoms, and laboratory indexes were collected. Patients were categorized into RA-only group and RA-ILD group with or without the occurrence of ILD disease. After data preprocessing, subjects were randomly assigned to the modeling and validation groups in a 7:3 ratio.Univariate analysis comparing baseline characteristics of the two groups of patients. Feature selection was performed using LASSO and SVM-RFE regression algorithms.Screening indicators were analyzed by logistic regression and the results were used to develop a nomograms model for the early diagnosis of RA complicating interstitial lung disease; and the modeling group was evaluated for its performance for internal assessment of the model and internal validation using data from the validation group.Results:A total of 712 subjects participated in the study, of which 498 in the modeling group and 214 in the validation group. Univariate analysis showed that the differences between the two groups were statistically significant ( P<0.05) in 18 characteristic indexes, including male, gender, age, smoking history, drinking history, number of swollen joints, number of painful joints, use of prednisone, WBC, ESR, CRP, IL-2, IL-10, IL-17, TNF-α, INF-γ, AFA family, APF, and serum albumin. The LASSO algorithm identified 13 risk variables for RA-ILD, the SVM-RFE algorithm identified 12 variables for RA-ILD, and the intersecting risk variables were male, age, history of alcohol consumption, number of painful joints, prednisone acetate, IL-2, AFA family, TNF-α, serum albumin, and IL-10. The results of multifactorial logistic regression analysis confirmed that the differences between males [ OR(95% CI)=3.61(2.11, 6.18)], gender, age [ OR(95% CI)=1.05(1.03, 1.08)], number of painful joints [ OR(95% CI)=1.03(1.01, 1.06)], IL-2 [ OR(95% CI)=0.91 (0.84, 0.99)], and TNF-α[ OR (95% CI)=1.06 (1.02, 1.10)] were statistically significant ( P<0.05) and were independently influences on ILD complicated by RA. The modeling and validation groups that were used to construct early diagnostic Nomograms had high calibration curve accuracies, and the model had a high diagnostic power, which was mainly demonstrated by the receiver operating characteristic (ROC) area under the curve (AUC) and decision curve analysis(DCA), the model modeling group had an AUC of 0.76 (95% CI=0.71, 0.81), with net benefit rates of 3%~82% and 93%~99%, whereas the model validation group had an AUC of 0.71 (95% CI=0.64, 0.79), with net benefit rates of 5%~11%, 14%~60% and 85%~89%. Conclusion:Male, gender, age, number of painful joints, IL-2, and TNF-α are independent factors for RA complicated with ILD, and the Nomogram model constructed has good performance in early diagnosis of the disease.
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Objective:The potential mechanism of cortex phellodendri chinsis in the improvement of rheumatoid arthritis (RA) through ferroptosis was analyzed based on network pharmacology.Methods:The main active components and their corresponding target proteins were screened by TCMSP database and Herb database, and the UniProt database was used to convert the corresponding target protein names into gene IDs. The targets of RA disease were obtained from GenCards, OMIM, DrugBank and DisGeNET databases. The FerrDb database was used to collect genes for Driver, Suppressors and Markers of ferroptosis. Then, Venny platform was used to obtain the intersection genes of Cortex phellodendri chinsis, RA and ferroptosis, and Cytoscape 3.9.1 software was used to plot the "active component-target-RA-ferroptosis" network diagram. Protein-protein interaction (PPI), gene ontology (GO) function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using String and DAVID databases. PyMOL, AutoDock Vina software and RCSB PDB database were used for molecular docking between active ingredients and key genes.Results:A total of 11 active components (Quercetin, Beta-sitosterol, Melianone, Candletoxin A, Phellochin, Palmidin A, Worenine, Hispidone, Kihadalactone A, Niloticin, Stigmasterol) and 34 intersection genes (PTGS2、AR、JUN、PRKCA、TGFB1、EGFR、CDKN1A、MAPK1、RB1、IL6、TP53、HIF1A、HSPA5、HMOX1、CAV1、IFNG、ALOX5、PTEN、NFE2L2、PARP1、PPARA、GSTM1、MTOR、PIK3CA、MDM2、MAPK8、GSK3B、SIRT1、DHODH、EZH2、AKR1C2、AKR1C1、STAT3、MAPK3) were screened. Ten possible targets of Cortex phellodendri chinsis regulating ferroptosis and anti-RA were predicted, including TP53、JUN、STAT3、HIF1A、PTEN、SIRT1、EGFR、MTOR、MAPK3、AR. Ferroptosis pathway is regulated by mediating positive regulation of gene expression, response to drugs, HIF-1, FoxO, ErbB and other signaling pathways, thus combating the occurrence and progression of RA. The docking results showed that there were molecular binding sites between the key genes and their corresponding active components.Conclusion:Cortex phellodendri chinsis may treat RA through ferroptosis effect with multiple components, multiple targets, multiple pathways and mechanisms.
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SUMMARY OBJECTIVE: Patients with rheumatic diseases have an increased risk of infections, especially tuberculosis. In this study, we aimed to recognize the positivity rate of tuberculosis skin test in patients with rheumatoid arthritis and spondyloarthritis and the characteristics of the patients with positive results. METHODS: Retrospective study of tuberculosis skin test results in patients followed from 2004 to 2021 in a single rheumatology unit. Data related to clinical and epidemiological features, along with treatment information referring to the period in which the tuberculosis skin test was performed, were collected from patients' charts. RESULTS: A total of 723 tests were identified (448 tests in 269 rheumatoid arthritis patients and 275 in 174 spondyloarthritis patients). In the rheumatoid arthritis sample, 31/275 (11.5%) individuals had positive tests, and in the spondyloarthritis, 38/174 (21.8%) had positive tests. In the rheumatoid arthritis sample, patients with positive tuberculosis skin tests used a higher dose of methotrexate than those with negative results (median of 25 mg/week versus median of 20 mg/week respectively; p=0.02). In the spondyloarthritis sample, tuberculosis skin test positivity was associated with alcohol ingestion (13.1% versus 2.9% in users and non-users respectively; p=0.02) and sulfasalazine use (15.7% of positivity in users versus 5% in non-users; p=0.01). CONCLUSION: The tuberculosis skin test-positive prevalence in rheumatoid arthritis was lower than in the spondyloarthritis sample. Patients with rheumatoid arthritis using a higher dosage of methotrexate or with spondyloarthritis using sulfasalazine had more frequency of tuberculosis skin test positivity and should be carefully followed by the attending physician in order to avoid the appearance of full-blown tuberculosis.
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ABSTRACT Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.
RESUMO Doença pulmonar intersticial associada à doença do tecido conjuntivo (DPI-DTC) representa um grupo de distúrbios autoimunes sistêmicos caracterizados por disfunção de órgãos imunomediada. Esclerose sistêmica, artrite reumatoide, miosite inflamatória idiopática e síndrome de Sjögren são as DTC mais comuns que apresentam acometimento pulmonar, bem como pneumonia intersticial com achados autoimunes. A frequência de DPI-DTC varia de acordo com o tipo de DTC, mas a incidência total é de 15%, causando um impacto importante na morbidade e mortalidade. A decisão sobre qual paciente com DTC deve ser investigado para DPI não é clara para muitas DTC. Além disso, o espectro clínico pode variar desde achados assintomáticos em exames de imagem até insuficiência respiratória e morte. Parte significativa dos pacientes apresentará doença mais grave e progressiva, e, para esses pacientes, imunossupressão com corticosteroides e medicamentos citotóxicos são a base do tratamento farmacológico. Nesta revisão, resumimos a abordagem do diagnóstico e tratamento de DPI-DTC, destacando os recentes avanços na terapêutica para as diversas formas de DTC.
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Fundamento: la artritis reumatoidea es una enfermedad autoinmunitaria crónica que produce daño articular crónico e irreversible que conlleva al deterioro de la calidad de vida y discapacidad permanente con prevalencia mundial de entre 1,0 y 1,5 %. Objetivo: identificar las principales características clínico-epidemiológicas de pacientes con artritis reumatoidea en el Policlínico Docente Área Este de Camagüey. Métodos: se realizó un estudio descriptivo, de serie de casos, realizado en el Policlínico Docente Área Este de Camagüey. Del universo de 108 pacientes fue seleccionada una muestra de 102, una vez aplicados los criterios de elección. Se estudiaron las variables: grupo etáreo, sexo, color de la piel, años de diagnóstico, signos y síntomas clínicos, factores de riesgo; así como complicaciones presentadas. Para el procesamiento de los datos se empleó SPSS y se expresaron en valores absolutos y porcentajes. Resultados: predominó el grupo etáreo de 60 años y más (45,0 %), las mujeres (75,5 %), pacientes de color de piel blanca (66,7 %), con artritis reumatoidea de 16-20 años de evolución (22,5 %), vasculitis (25,5 %) y dolor (94,1 %) dentro de los principales signos y síntomas, mientras el consumo de café (69,6 %) y el sexo femenino se encontraron dentro los factores de riesgo modificables y no modificables. La osteoporosis fue la más notable de las complicaciones presentadas (69,6 %). Conclusiones: en la serie estudiada sobresalió el sexo femenino, la edad avanzada, el dolor como síntoma principal, así como la osteoporosis dentro de las complicaciones presentadas.
Foundation: rheumatoid arthritis is a chronic autoimmune disease that produces chronic and irreversible joint damage that leads to deterioration in quality of life and permanent disability with a worldwide prevalence of between 1.0 and 1.5 %. Objective: to identify the main clinical-epidemiological characteristics of patients with rheumatoid arthritis in the Eastern Area Teaching Polyclinic of Camagüey. Methods: a descriptive case series study was carried out at the Eastern Area Teaching Polyclinic of Camagüey. From the universe of 108 patients, a sample of 102 was selected, once the selection criteria were applied. The variables were studied: age group, sex, skin color, years of diagnosis, clinical signs and symptoms, risk factors; as well as complications presented. SPSS was used to process the data and they were expressed in absolute values and percentages. Results: the age group of 60 years and older predominated (45.0 %), women (75.5 %), patients of white skin color (66.7 %), with rheumatoid arthritis of 16-20 years of evolution (22.5 %), vasculitis (25.5 %) and pain (94.1 %) among the main signs and symptoms, while coffee consumption (69.6 %) and female sex were found among the risk factors. modifiable and non-modifiable risk. Osteoporosis was the most notable of the complications presented (69.6 %). Conclusions: in the series studied, female sex, advanced age, pain as the main symptom, as well as osteoporosis stood out among the complications presented.
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La artritis reumatoide es una enfermedad progresiva, con manifestaciones clásicas y tempranas como es la afectación de las articulaciones pequeñas de las manos y los tobillos. Se realizó una revisión bibliográfica de los documentos publicados entre 2017 y 2022. Se realizó una lectura preliminar de 37 artículos que cumplían con los criterios de inclusión, y finalmente se seleccionaron 23 artículos, de los cuales se tomó el contenido de mayor importancia. La ecografía es una técnica fiable y más sensible que la exploración clínica en el estudio de la enfermedad músculo-esquelética, pues permite una exploración multiplanar y dinámica, lo que resulta en un diagnóstico más exacto. La técnica Doppler constituye un complemento útil en el seguimiento de estos pacientes. Esta enfermedad es recurrente en las consultas de Reumatología, por tanto, en su valoración inicial, la utilidad de los medios diagnósticos, especialmente la ecografía, tiene gran importancia.
Rheumatoid arthritis is a progressive disease, with classic and early manifestations such as involvement of the small joints of the hands and ankles. We conducted a bibliographic review of the documents published between 2017 and 2022. A preliminary reading of 37 articles that met the inclusion criteria was carried out, and 23 articles were finally selected, from which the most important content was taken. Ultrasound is a more sensitive and reliable technique than clinical examination for the study of musculoskeletal disease, since it allows a multiplanar and dynamic examination, which results in a more accurate diagnosis. Doppler technique is a useful complement in the follow-up of these patients. This disease is recurrent in Rheumatology consultations, that's why in its initial assessment, the usefulness of diagnostic means, especially ultrasound, is of great importance.
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Arthritis, Rheumatoid , Rheumatology , Echocardiography, DopplerABSTRACT
Introduction: The most important genetic association in rheumatoid arthritis (RA) is presented with some alleles from the HLA-DRB1 gene that encode the shared epitope (SE). Objectives: To apply the SE classification methods of Gregersen, de Vries, Raychaudhuri, Mattey, and Tezenas du Montcel in a group of Colombian patients with RA and determine the most common HLA-DRB1 alleles in the population. Methods: RA diagnosis, genetic study of the HLA-DRB1 region using Luminex technology in 50 RA and 50 healthy subjects. For the classification analysis, Fisher's exact test and chi-squared test were applied. Tables were created to count the RA-related alleles. We used odds ratio to determine the risk between the presence of the shared epitope (SE) and anti-cyclic citrullinated peptides (Anti-CCP). Results: Gregersen and de Vries methods were suitable for the characterization of RA in this population (p = .006). The most prevalent HLA-DRB1 alleles in the RA group were 14:02,04:04, 08:02,04:05, and 10:01. High frequencies of the 07:01, 03:01,13:02,01:02, and 12:01 HLA-DRB1 alleles were found in the healthy population. HLA-DRB1 alleles with similar distribution in both populations were 04:07, 15:01, 11:01, 16:02, and 01:01. A high frequency of SE + was observed in Anti-CCP + individuals (63.15%); however, this was not statistically significant [OR2.4 (.63-9.01); p = .19]. Conclusion: The SE classification methods of Gregersen and de Vries were adequate in characterizing RA in a Colombian population group. An equivalence of 100% was verified between the susceptibility alleles defined by de Vries and the alleles assigned as SE according to Gregersen.
Introducción: La asociación genética más importante en artritis reumatoide (AR) se presenta con algunos alelos del gen HLA DRB1 que codifican el epítope compartido (EC). Objetivos: Aplicar los métodos de clasificación de EC de Gregersen et al., de Vries et al., Raychaudhuri et al., Mattey et al., y Tezenas du Montcel et al., en un grupo de pacientes colombianos con AR, y determinar los alelos HLA DRB1 más frecuentes en esta población. Métodos: Diagnóstico para AR, estudio genético de la región HLA DRB1 por tecnología Luminex® de 50 sujetos AR y 50 sanos. Para análisis comparativos de clasificaciones EC, se aplicaron las pruebas test exacto de Fisher y Chi-cuadrado y se realizaron tablas de conteos para los alelos relacionados con AR. Se estimó la razón de odds para determinar el riesgo entre la presencia de EC y los anticuerpos antipéptidos cíclicos citrulinados (anti-PCC). Resultados: Los métodos de Gregersen et al. y de Vries et al. fueron adecuados para la caracterización de AR en esta población (p = 0,006). Los alelos HLA DRB1 más prevalentes en el grupo AR fueron 14:02, 04:04, 08:02, 04:05 y 10:01. Se encontraron altas frecuencias de los alelos HLA DRB1 07:01, 03:01,13:02, 01:02 y 12:01 en población sana. Alelos HLA DRB1 con distribución similar en ambas poblaciones fueron: 04:07, 15:01, 11:01, 16:02 y 01:01. Se observó alta frecuencia de individuos EC+ en el grupo AR anti-PCC+ (63,15%); no obstante, sin asociación estadística (OR: 2,4 [0,63-9,01]; p = 0,19). Conclusión: Los métodos de clasificación para EC de Gregersen et al. y de Vries et al. fueron adecuados caracterizando AR en un grupo de población colombiana. Se corroboró equivalencia del 100% entre los alelos de susceptibilidad definidos por de Vries y los alelos asignados como EC según Gregersen et al.
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Humans , Male , Female , Adult , Middle Aged , Aged , Arthritis, Rheumatoid , Biological Factors , Musculoskeletal Diseases , Joint Diseases , Epitopes , AntigensABSTRACT
Introducción : El complejo C0-C1-C2 es responsable de la transición de la carga axial, con función biomecánica única, siendo afectada por múltiples patologías, que por lo general la literatura no las considera como un solo ítem, sino que lo desarrolla según su etiología, pero en nuestro estudio se ha considerado en 5 grupos: traumática, congénita, inflamatoria reumática, neoplásica y degenerativa. Objetivo : Determinar las características epidemiológicas, clínicas y del tratamiento en la patología cervical alta. Materiales y métodos : Se incluyeron a todos los pacientes con diagnóstico clínico radiológico de alguna patología cervical alta que hayan sido sometidos a tratamiento quirúrgico entre 2016 y 2021 en el Hospital Almenara. Se usó el test "t" de student y de chi cuadrado. Se dividió a los pacientes en alguno de los 5 grupos antes mencionados. Resultados : Se consideraron 31 pacientes, con una edad media de 51.16 años. La patología cervical alta más frecuente fue la traumática con el 35.48%. El déficit motor se presentó en el 51.61% y el déficit sensitivo se presentó en el 54.84%. La cirugía más frecuente fue la fijación cervical alta con el 43.89%. La tasa de complicaciones fue del 16.13% con una mortalidad del 0%. Conclusiones : La patología cervical alta es rara, siendo la del tipo traumática la más frecuente, pero un manejo oportuno y adecuado permite un mejor pronóstico funcional del paciente.
Introduction : The C0-C1-C2 complex is responsible of axial load transition, and its biomechanical function is unique, it is affected by multiple pathological conditions; and generally speaking, the literature does not consider these conditions as a single item, it describes them according to etiology. For our study we considered five groups: trauma-related, congenital, rheumatic-inflammatory, neoplastic, and degenerative. Objective : To determine epidemiological, clinical, and therapy-related characteristics in upper cervical pathological conditions. Materials and methods : All patients with a clinical-radiological diagnosis of any upper cervical pathological condition that had undergone surgery between 2016 and 2021 in Guillermo Almenara Hospital were included. Student's t test and chi square methods were used. patients were divided into one of the five aforementioned groups. Results : Thirty-one patients were included in the study; their mean age was 51.16 years. The most frequent upper cervical pathological condition was trauma-related, with 35.48%. Motor deficit occurred in 51.61% of all patients, and sensitive deficit occurred in 54.84%. The most frequently surgical procedure performed was upper cervical fixation, in 43.89% of all patients. Complication rate was 16.13%, and mortality was 0%. Conclusions : Upper cervical pathological conditions are rare, trauma-related conditions are most frequent, but timely and adequate management allow us to achieve better functional prognosis for these patients.
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Rheumatoid arthritis (RA) is a group of heterogeneous autoimmune diseases with erosive arthritis as the main clinical feature. The pathogenesis of RA remains unclear. Autoantibodies can be detected in blood or synovial fluid in approximately 70% of patients with RA in the early stage of the disease. Anti-citrullinated protein antibody (ACPA) is the most commonly used autoantibody in the diagnosis of RA. However, ACPA is not a specific antibody for RA. The discovery and clinical application of serum ACPA-negative RA biomarkers is of positive significance for the early diagnosis and prognosis improvement of RA. This paper reviews the research progress of ACPA-negative RA biomarkers.
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Objective:To investigate the effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor (RF) level and morning stiffness time in patients with refractory rheumatoid arthritis (RA).Methods:A total of 120 patients with refractory RA diagnosed and treated in the First Affiliated Hospital of Hebei North University from June 2019 to June 2020 were selected as the study subjects, and they were randomly divided into three groups by random number table method: etanercept group, etanercept+ methotrexate group, and tofacitinib+ methotrexate group, with 40 patients in each group. The etanercept group was given etanercept treatment, the etanercept+ methotrexate group was given etanercept combined with methotrexate treatment, and the tofacitinib+ methotrexate group was given tofacitinib combined with methotrexate treatment. The clinical efficacy (12 W, 24 W and 48 W of treatment), disease activity, RF level, morning stiffness time and incidence of adverse reactions were compared among the three groups.Results:Comparison of the total clinical effective rate of the three groups: the total clinical effective rate of the etanercept+ methotrexate group and the tofacitinib+ methotrexate group was higher than that of the etanercept group (both P<0.05), and the tofacitinib+ methotrexate group was higher than that of the etanercept+ methotrexate group ( P<0.05). After treatment, the clinical symptoms and disease activity scores (DAS28) in the etanercept+ methotrexate and tofacitinib+ methotrexate groups were significantly improved compared with the etanercept group (all P<0.05), and the improvements in the tofacitinib+ methotrexate group were more significant than those in the etanercept+ methotrexate group ( P<0.05). After treatment, the erythrocyte sedimentation rate (ESR), RF and C-reactive protein (CRP) levels were lower in the etanercept+ methotrexate and tofacitinib+ methotrexate groups than those in the etanercept groups (all P<0.05), and the ESR, RF and CRP levels in the tofacitinib+ methotrexate groups were lower than those in the etanercept+ methotrexate group (all P<0.05). There was no significant difference in the incidence of total adverse reactions among 3 groups (7.50% vs 12.50% vs 12.50%) ( P>0.05). Conclusions:Tofacitinib combined with methotrexate can effectively improve the disease activity, RF level and morning stiffness time in patients with refractory RA, with high safety, which is worthy of clinical application and promotion.
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Objective:Rat model of RA complicated with pulmonary fibrosis were constructed to observe the degree of improvement of pulmonary fibrosis in RA rats by JAK2 inhibitor CEP33779 and the possible mechanisms.Methods:①The RA models were constructed by subcutaneous injection of 0.2 ml (1 mg/ml) of bovine type Ⅱ collagen into the tail of the rats on the day of modeling development (d0); intratracheal injection of 100 μl bleomycin (2.5 mg/kg) was used to induce pulmonary fibrosis model at d13. In vivo study: model rats were randomly divided into the normal group, pulmonary fibrosis group, pulmonary fibrosis CEP treatment group, RA complicated with pulmonary fibrosis group, and RA complicated pulmonary fibrosis CEP treatment group. Rats in the treatment group was given CEP (10 ml/kg) qd by gavage from d14 to week 4. The right hind foot of the rats was measured for joints swelling and the arthritis index score were measured, lung compliance (Cst) and lung specific gravity were measured. In addition, the pathological changes of the left lung were observed by HE and Masson staining, and the extracellular matrix level of the right lung was measured by protein immunoblotting (WB). ② In vitro study: TGF-β 1 (10 ng/ml) was applied to stimulate human embryonic lung fibroblasts (HFL1) for 24 h and 48h, and p-JAK2 expression was detected by immunofluorescence. After HFL1 inoculation of culture plates, the control group, TGF-β 1 stimulation group, TGF-β 1+ LY2109761 (TGFβ-R1/2 inhibitor group, 0.5 mmol/L and 2 mmol/L) group, TGF-β 1+CEP (0.1 mmol/L and 1.0 mmol/L) group were co-incubated for 48 h, and the expression levels of TGFβ-R2, α-SMA, JAK2, and Col 1 were measured by WB. Comparisons between multiple groups were made by Tukey′s test, and comparisons between the two groups were analyzed by independent t-test. Results:① In vivo study, compared with the control group (1.45±0.04), joint swelling was increased at d13 [(2.54±0.16) in RA+PF+Vehicle group, t=16.02, P<0.001], and the mean arthritis index score and toe volume were decreased 3 days after CEP treatment(d16) [(2.89±0.11), t=5.78, P<0.001; (1.92±0.13), t=6.85, P<0.001]. For rats with pulmonary fibrosis, all had different degrees of lung enlargement, increased lung specific gravity, decreased Cst, and increased lung inflammation and fibrosis[(0.96±0.06), t=19.76, P<0.001; (0.26±0.09), t=17.64, P<0.001; (3.63±1.51), t=6.00, P<0.001; (1.75±0.71), t=5.84, P<0.001]. After CEP gavage, rats that had RA complicated with pulmonary fibrosis had reduced lung swelling, decreased lung specific gravity, increased Cst [(0.82±0.05), t=5.76, P<0.001; (0.43±0.18), t=2.31, P=0.038], and the scores of pulmonary fibrosis and inflammation [(3.00±1.00); (1.56±0.52)] all showed a trend of decrease, but did not reach statistical difference CEP inhibited the expression of TGF-β 1, TGFβ-R2, α-SMA, Fn and JAK2 in lung tissue of pulmonary fibrosis rats, and the differences among the five groups were statistically significant ( F=9.02, P=0.017; F=4.86, P=0.048; F=6.57, P=0.032; F=11.26, P=0.010; F=13.32, P=0.007). ② In vitro study, TGF-β 1 stimulated HFL1 showed stronger phosphorylated JAK2 (p-JAK2) fluorescent signal WB showed a significant increase in the expression of TGFβ-R2, α-SMA, JAK2 and Col1, and after LY and CEP intervention, the above proteins were reduced in a concentration-dependent manner, with statistically significant differences among all five groups ( F=337.30, P<0.001; F=20.61, P<0.001; F=100.60, P<0.001; F=180.90, P<0.001). Conclusion:JAK2 inhibitors can ameliorate RA-related pulmonary fibrosis, and the mechanism may be through interfering with the "crosstalk" between JAK2 and TGF-β 1 signaling pathway.
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Objective:To improve the clinical differential diagnosis ability of rheumatoid arthritis (RA) complicated with gout and septic arthritis (SA).Methods:The clinical characteristics, diagnosis, and treatment of one RA patient with hyperuricemia and recurrent swelling and pain in right shoulder were reported and discussed.Results:A patient, with a history of RA for 10 years, hyperuricemia for 8 years, recurrent swelling and pain in right shoulder for 1 year. RA, gout, and SA were diagnosed before, and the response was poor after symptomatic treatment. In recent 1 month, the symptom was aggravated with the formation of fistula on the right shoulder. The laboratory tests for tuberculosis T cell interferon release test (IGRA) and tuberculin (PPD) test were negative, and the CD4 + cell count decreased. The comprehensive analysis of the imaging with right shoulder showed MSU deposition on right shoulder, with bone erosion, bone destruction, bone marrow edema, joint effusion, and multiple sites of connective tissue involvement (synovial bursa, tendon sheath, tendon, and muscle) GeneXpert MTB/RIF (GeneXpert), metagenomic next-generation sequencing (mNGS) of puncture fluid and joint fluid culture prompted Mycobacterium tuberculosis complex group. He was finally diagnosed with RA, gout, and osteoarticular tuberculosis (OAT). Symptoms were relieved after symptomatic treatment. Conclusion:RA patients with hyperuricemia have recurrent single arthritis. In addition to considering for gout, the presence of OAT should also be considered. The immune functional status of the patient and drug used may interfere with the interpretation of immune function tests. It is necessary to integrate the clinical characteristics of patients, a variety of imaging examinations, and etiological detection to confirm the diagnosis and avoid misdiagnosis.
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Objective:To explore the distribution characteristics of memory B cells and its relationship with bone erosion in patients with rheumatoid arthritis (RA), and to further understand the mechanism of B cells in the pathogenesis of RA.Methods:B cell subsets in peripheral blood of 200 RA patients and 50 healthy individuals were detected by flow cytometry. According to the surface markers CD19, CD27 and lgD, B cells were divided into CD19 +CD27 +lgD - switched memory B cells, CD19 +CD27 +lgD + non-switched memory B cells, CD19 +CD27 -lgD - double-negative memory B cells and CD19 +CD27 -lgD + naive B cells. B cells in RA patients with various disease activity score, course of disease and treatment were analyzed. Patients were divided into four groups according to the results of joint ultrasonography, including patients without bone erosion, patients with hand bone erosion, patients with knee bone erosion and patients with hand and knee bone erosion. The relationship between the distribution of B cell subsets, autoantibodies and RA bone erosion were analyzed. Differences between the groups were analyzed by independent-samples t test, Mann-Whitney U test and χ2 test. The analysis of variance, Kruskal-Wallis analysis were used for multi-group comparison, Spearman correlation analysis was also used for correlation analysis. Results:①RA patients showed significantly decreased non-switched memory B cells [(9.5±6.7)% vs (12.1±4.7)%, t=2.46, P=0.015] and increased double negative memory B cells [(3.8±2.5)% vs(2.7±1.3)%, t=-4.74, P<0.001] in comparison to healthy individuals. The percentage of non-switched memory B cells were decreased in RA patients with moderate disease activity [(8.4±4.7 )% vs (12.4±7.5)%, t=3.13, P=0.001] and high disease activity [(7.8±7.6)% vs (12.4±7.5)%, t=3.00, P=0.003] in comparison to those in RA patients who achieved remission. Meanwhile, the na?ve B cells [(70.3±15.0)% vs (63.9±14.6)%, t=-2.15, P=0.034] were increased in RA patients with moderate disease activity. No difference was found in RA patients with different disease courses. Total B cells [(4.8±2.9)% vs (7.2±4.1)%, t=-3.24, P=0.001], non-switched memory B cells (7.6±4.3)% vs (10.0±7.1)%, t=-2.63, P=0.010) in RA patients who received prednisone treatment were decreased, while double-negative memory B cells (4.9±3.0)% vs (3.6±2.3)%, t=-2.79, P=0.006] were increased compared with those in RA patients without prednisone treatment. Non-switched memory B cells was decreased in RA patients with hand and knee erosion compared with RA patients without erosion [6.8%(2.5%, 9.5%) vs 9.7%(5.5%, 17.5%), Z=-2.12, P=0.034]. Double negative memory B cells in subgroup with keen erosion [3.3%(2.7%, 5.0%) vs 2.6%(1.9%, 3.8%), Z=-2.09, P=0.036]as well as with hand and knee erosion [3.9%(2.3%, 5.6%) vs 2.6%(1.9%, 3.8%), Z=-2.41, P=0.016] were higher than those in patients without erosion. In addition, higher serum RF level was found in subgroup RA patients with hand and knee erosion compared with subgroup of RA patients without erosion [141.0 (38.0, 874.0) U/ml vs 53.5 (10.0, 106.0)U/ml, Z=-2.07, P=0.039]. Meanwhile, the positive rate of ACPA in RA patients with bone erosion of hand was significantly higher than that of RA patients without bone erosion [81%(52/64) vs 64%(38/59), χ2=4.44, P=0.043). Conclusions:The results suggest that the increase of double negative memory B cells, the decrease of non-switched memory B cells and higher level of autoantibodies may closely relate to bone erosion of RA, which may be one of the pathogenesis of disability in RA.
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Objective:To explore the impact of clinical features, serological indicators, and pulmonary function test (PFT) on the prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Methods:Clinical data of RA-ILD patients who were diagnosed by HRCT and were followed up in Changhai Hospital or Yancheng First People's Hospital from 2011 to 2021 were collected Respiratory functional impairment of the patients was evaluated according to the changes of HRCT score and PFT, and the patients were divided into progressive group and stable group. COX survival analysis and ROC curve were used to determine the factors related to the progression of RA-ILD.Results:Finally 98 RA-ILD patients were included. The mean age of ILD onset was (62.9±12.1) years old, the median course of RA was 7.0 (1.0, 15.3)years, and the median follow-up time was 36.5 months (14.0, 79.5). There were 49 cases in the progressive group, and the clinical characteristics and laboratory tests of the two groups were compared. The results showed that: progressive time [(23(8.5,43.0)months vs 63(32.5,90.9) months, Z=-4.55, P=0.001)], HRCT score [(115(109,135) vs 111(105,116), Z=-2.70, P=0.007)], forced vital capacity(FVC) predicted [(70.1±15.7)% vs (80.8±19.7)%, t=2.12, P=0.039)], diffusing capacity of the lungs for CO(DLCO) predicted [(57.5±16.3)% vs (83.4±18.8)%, t=4.87, P=0.001)], male [(44.9% vs 18.4%, χ2=7.97, P=0.005)], UIP pattern [(36(73.5%) vs 9(18.4%), χ2=29.96, P<0.001)], RF>200 U/ml[(21(65.6%) vs 18(41.9%), χ2=4.15, P=0.042)], anti-CCP>75 U/ml [(42(91.3%) vs 35(71.4%), χ2=6.10, P=0.013], all had significantly different between the two groups. In multivariate analyses, UIP[ HR(95% CI)=3.25(1.62,6.50), P<0.001], anti-CCP antibody >75 U/ ml[ HR(95% CI)=3.85 (1.20,12.33), P=0.023] and smoking [ HR (95% CI): 5.74(1.10, 30.13), P=0.039] were significantly correlated with the progression of pulmonary fibrosis in RA-ILD patients. PFT was performed in only 44 patients with RA-ILD. The univariate analyses and ROC curve suggested that DLCO predicted [ HR (95% CI)=1.04 (1.02,1.06), P<0.001] was a significant risk factor for the progression of RA-ILD, and the area under curve (AUC) of DLCO was 0.845 [95% CI=(0.729,0.961)]. Conclusion:UIP pattern, high titer of anti-CCP antibody, smoking, and reduced DLCO predicted % may be potential predictors for poor prognosis of RA-ILD patients.