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1.
Cytokine ; 159: 156026, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36084603

RESUMO

BACKGROUND: Meteorin-like (Metrnl) is a novel adipokine that is highly expressed in white adipose tissues. Whether Metrnl plays a role in rheumatoid arthritis (RA) remains unclear. In this study, sera from 159 RA patients, 28 osteoarthritis (OA) patients, and 50 healthy individuals were included. The serum levels of Metrnl were measured using an enzyme-linked immunosorbent assay. Clinical parameters, including disease activity score 28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), antibodies to cyclic citrulline peptide (anti-CCP), inflammatory cytokines, and blood biochemical indices were collected. RESULTS: Metrnl levels were higher in RA patients compared to OA patients and controls. In the RA group, serum Metrnl levels were positively correlated with DAS28, RF, and CRP levels. However, in the RA group, serum Metrnl levels were not correlated with ESR, anti-CCP, immunoglobulins, and blood biochemical indices. CONCLUSION: This study showed that Metrnl is involved in the pathogenesis of RA. Increase in serum Metrnl levels is closely related to RA activity.


Assuntos
Artrite Reumatoide , Osteoartrite , Adipocinas , Anticorpos Anti-Proteína Citrulinada , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Citrulina , Citocinas , Humanos , Peptídeos Cíclicos , Fator Reumatoide
2.
Arthritis Res Ther ; 24(1): 220, 2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088336

RESUMO

BACKGROUND: The IL-23/IL-17 axis is involved in inflammatory diseases including arthritis and psoriasis. However, the response to IL-23 or IL-17 inhibitors is different depending on the disease. The aim was to compare the effects of interactions between immune and stromal cells on the IL-23 axis to understand these differences. METHODS: Peripheral blood mononuclear cells were co-cultured with RA synoviocytes or Pso skin fibroblasts, with or without phytohemagglutinin, IL-23, or anti-IL-23 antibody. Production of IL-6, IL-1ß, IL-23, IL-17, IL-12, and IFNγ was measured by ELISA. IL-23 and cytokine receptor gene expression (IL-17RA, IL-17RC, IL-12Rß1, IL-12Rß2, and IL-23R) was analyzed by RT-qPCR. IL-12Rß1 and IL-23R subunits were analyzed by flow cytometry. RESULTS: The production of IL-6, IL-1ß, IL-17, IL-12, and IFNγ with synoviocytes or skin fibroblasts was rather similar, and cell interactions with immune cells increased their production, specifically that of IL-17. A major difference was observed for IL-23. Interactions with synoviocytes but not with skin fibroblasts decreased IL-23 secretion while mRNA level was increased, mainly with synoviocytes, reflecting a major consumption difference. IL-23 addition had only one effect, the increase of IL-17 secretion. Cell activation induced similar effects on cytokine receptor gene expression in co-cultures with synoviocytes or skin fibroblasts. The key difference was the cell interaction effects depending on the stromal cell origin. Interactions with synoviocytes increased the expression of both IL-23 receptor subunits at mRNA levels and IL-23R at the surface expression level while interactions with skin fibroblasts decreased their expression at the mRNA level and had no effect at the surface expression level. CONCLUSION: Interactions between immune and stromal cells are crucial in cytokine production and their receptor expression. The origin of stromal cells had a major influence on the production of IL-23 and its receptor expression. Such differences may explain part of the heterogeneity in treatment response.


Assuntos
Artrite Reumatoide , Sinoviócitos , Comunicação Celular , Fibroblastos/metabolismo , Expressão Gênica , Humanos , Interleucina-12 , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , RNA Mensageiro , Sinoviócitos/metabolismo
3.
Arthritis Res Ther ; 24(1): 218, 2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088424

RESUMO

BACKGROUND: Pain is the main concern of patients with rheumatoid arthritis (RA) while reducing disease activity dominates specialist management. Disease activity assessments like the disease activity score for 28 joints with the erythrocyte sedimentation rate (DAS28-ESR) omit pain creating an apparent paradox between patients' concerns and specialists' treatment goals. We evaluated the relationship of pain intensity and disease activity in RA with three aims: defining associations between pain intensity and disease activity and its components, evaluating discordance between pain intensity and disease activity, and assessing temporal changes in pain intensity and disease activity. METHODS: We undertook secondary analyses of five trials and one observational study of RA patients followed for 12 months. The patients had early and established active disease or sustained low disease activity or remission. Pain was measured using 100-mm visual analogue scales. Individual patient data was pooled across all studies and by types of patients (early active, established active and established remission). Associations of pain intensity and disease activity were evaluated by correlations (Spearman's), linear regression methods and Bland-Altman plots. Discordance was assessed by Kappa statistics (for patients grouped into high and low pain intensity and disease activity). Temporal changes were assessed 6 monthly in different patient groups. RESULTS: A total of 1132 patients were studied: 490 had early active RA, 469 had established active RA and 173 were in remission/low disease activity. Our analyses showed, firstly, that pain intensity is associated with disease activity in general, and particularly with patient global assessments, across all patient groups. Patient global assessments were a reasonable proxy for pain intensity. Secondly, there was some discordance between pain intensity and disease activity across all disease activity levels, reflecting similar discrepancies in patient global assessments. Thirdly, there were strong temporal relationships between changes in disease activity and pain intensity. When mean disease activity fell, mean pain intensity scores also fell; when mean disease activity increased, there were comparable increases in pain intensity. CONCLUSIONS: These findings show pain intensity is an integral part of disease activity, though it is not measured directly in DAS28-ESR. Reducing disease activity is crucial for reducing pain intensity in RA.


Assuntos
Artrite Reumatoide , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/terapia , Sedimentação Sanguínea , Humanos , Dor/etiologia , Medição da Dor/métodos , Índice de Gravidade de Doença
4.
Reumatismo ; 74(2)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36101991

RESUMO

Since COVID-19 vaccination started in December 2020, different side effects were reported. This case report describes the possibility of developing disseminated herpes simplex infection after COVID-19 vaccine in a patient with rheumatoid arthritis. In this case report, we describe a 63-year-old Iranian female. She was a known case of seronegative rheumatoid arthritis and presented with generalized papulo-pustular itchy and painful skin lesions which appeared about seven days after the second dose of Sinopharm BIBP COVID-19 vaccine (BIBP-CorV). A biopsy of the skin lesions revealed acantholysis, neutrophils, and enlarged keratinocytes with eosinophilic intra-nuclear inclusions. Findings were consistent with herpes simplex infection. She was successfully treated by acyclovir. Disseminated cutaneous herpes simplex infection may have been triggered by COVID-19 vaccination. Reactivation of herpes virus after COVID-19 vaccines was reported in both rheumatic patients and other individuals. Whether having an underlying autoimmune inflammatory disorder could be an additional risk factor is still unknown.


Assuntos
Artrite Reumatoide , Vacinas contra COVID-19 , COVID-19 , Herpes Simples , Dermatopatias , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Herpes Simples/tratamento farmacológico , Herpes Simples/etiologia , Herpes Simples/patologia , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , Vacinação/efeitos adversos
5.
BMC Public Health ; 22(1): 1768, 2022 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115952

RESUMO

Considering the female preponderance of rheumatoid arthritis (RA), and disease onset typically after the reproductive years, pregnancy and childbirth may play a role in the aetiology of the disease. Adverse outcomes of pregnancy have been found to precede the diagnosis of autoimmune diseases, including RA, but the evidence is scant and inconsistent. Therefore, we investigate whether pregnancy loss is associated with the risk of RA in Chinese women. Data from the China Kadoorie Biobank, conducted by the University of Oxford and the Chinese Centre for Disease Control and Prevention, of 299,629 Chinese women who had been pregnant were used. Multivariable logistic regression and stratified analyses were employed to analyse the association between types of pregnancy loss with the risk of RA. Pregnancy loss was significantly associated with increased risk of RA (OR 1.12, 95% CI 1.06-1.18), specifically, spontaneous (OR 1.11, 95% CI 1.03-1.20) and induced abortions (OR 1.11, 95% CI 1.06-1.17). There was no significant association between stillbirth and the risk of RA (OR 1.07, 95% CI 0.97-1.18). The risk of developing RA increases with the number of pregnancy losses: one loss confers an OR of 1.09 (95% CI 1.03-1.16), two an OR of 1.13 (95% CI 1.05-1.20), three or more an OR of 1.19 (95% CI 1.10-1.28) and OR of 1.06 (95% CI 1.03-1.08) for each additional. Spontaneous and induced abortions are associated with an increased risk of RA in Chinese women.


Assuntos
Aborto Induzido , Aborto Espontâneo , Artrite Reumatoide , Aborto Espontâneo/epidemiologia , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Bancos de Espécimes Biológicos , Feminino , Humanos , Gravidez , Natimorto/epidemiologia
6.
Front Immunol ; 13: 961129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110846

RESUMO

Background: Rheumatoid arthritis (RA) is the most common inflammatory arthropathy. Immune dysregulation was implicated in the pathogenesis of RA. Thus, the aim of the research was to determine the immune related biomarkers in RA. Methods: We downloaded the gene expression data of RA in GSE89408 and GSE45291 from Gene Expression Omnibus public database (GEO). Differentially expressed genes (DEGs) were identified between RA and control groups. Infiltrating immune cells related genes were obtained by ssGSEA and weighted gene co-expression network analysis (WGCNA). We performed functional enrichment analysis of differentially expressed immunity-related genes (DEIRGs) by "clusterProfiler" R package, key genes screening by protein-protein interaction (PPI) network of DEIRGs. And mice collagen-induced arthritis (CIA) model was employed to verify these key genes. Results: A total of 1,885 up-regulated and 1,899 down-regulated DEGs were identified in RA samples. The ssGSEA analysis showed that the infiltration of 25 cells was significantly different. 603 immune related genes were obtained by WGCNA, and 270 DEIRGs were obtained by taking the intersection of DEGs and immune related genes. Enrichment analyses indicated that DEIRGs were associated with immunity related biological processes. 4 candidate biomarkers (CCR7, KLRK1, TIGIT and SLAMF1) were identified from the PPI network of DEIRGs and literature research.In mice CIA model, the immunohistochemical stain showed SLAMF1 has a significantly high expression in diseased joints. And flow cytometry analysis shows the expression of SLAMF1 on CIA mice-derived CTL cells, Th, NK cells, NKT cells, classical dendritic cell (cDCs) and monocytes/macrophages was also significantly higher than corresponding immune cells from HC mice. Conclusion: Our study identified SMLAF1 as a key biomarker in the development and progression of RA, which might provide new insight for exploring the pathogenesis of RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Artrite Experimental/genética , Artrite Reumatoide/metabolismo , Biomarcadores , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Camundongos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Receptores CCR7/genética , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária
7.
Arthritis Res Ther ; 24(1): 222, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114544

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) patients present with abnormal methylation patterns in their fibroblast-like synoviocytes (FLS). Given that DNA demethylation is critical for producing DNA methylation patterns, we hypothesized that DNA demethylation may facilitate RA progression. Therefore, we designed this study to examine the role of DNA dioxygenase family, Ten-Eleven translocation (TET1/2/3), in the pathological process of RA. METHODS: Synovial tissues and FLS were obtained from patients with RA and Osteoarthritis. K/BxN serum-induced arthritis was induced in Wild-type (WT) and TET3 heterozygous-deficient (TET3+/-) C57BL/6 mice. RESULTS: We found that both TET3 and 5-hydroxymethylcytosine (5hmC) were upregulated in synovitis tissues from RA patients and confirmed this upregulation in the cultured FLS derived from synovitis tissues. Tumor necrosis factor α (TNFα) upregulated TET3 and 5hmC levels in cultured FLS, and the stimulated FLS exhibited high cell mobility with increased transcription of cellular migration-related factors such as C-X-C motif chemokine ligand 8 (CXCL8) and C-C motif chemokine ligand 2 (CCL2) in a TET3-dependent manner. In addition, TET3 haploinsufficiency lowered RA progression in a mouse model of serum-induced arthritis. CONCLUSIONS: Based on these findings, we can assume that TET3-mediated DNA demethylation acts as an epigenetic regulator of RA progression.


Assuntos
Artrite Reumatoide , Dioxigenases , Sinovite , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Quimiocinas , DNA , Dioxigenases/genética , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa
8.
Semin Hematol ; 59(3): 123-130, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36115688

RESUMO

T cell large granular lymphocyte leukemia (T-LGLL) is an interesting case at the intersection of autoimmunity and cancer. In T-LGLL, T cells with somatic pathogenic mutations (mainly in STAT3) are linked to rheumatoid arthritis (RA) and neutropenia. A rare subtype of RA, Felty's syndrome, exhibits overlapping clinical features and comparable frequencies of activating STAT3 mutations in T cells as T-LGLL, which hints at a potential T-LGLL-Felty's syndrome-RA axis. Somatic mutations could shed light on the unexplained pathologies of these disorders. However, the causality of somatic mutations-do somatic mutations in immune cells cause inflammation, or does prolonged inflammation predispose to mutagenesis-remains unanswered. This review will focus on the recent advances in understanding somatic mutations in T-LGLL and related autoimmune conditions as a master regulatory network that sustains lymphoproliferation and inflammation.


Assuntos
Artrite Reumatoide , Síndrome de Felty , Leucemia Linfocítica Granular Grande , Artrite Reumatoide/complicações , Artrite Reumatoide/genética , Síndrome de Felty/genética , Síndrome de Felty/patologia , Humanos , Inflamação , Leucemia Linfocítica Granular Grande/genética , Leucemia Linfocítica Granular Grande/patologia , Mutação
9.
BMC Public Health ; 22(1): 1678, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064372

RESUMO

BACKGROUND: Occupational exposures may result in Canadian military Veterans having poorer health and higher use of health services after transitioning to civilian life compared to the general population. However, few studies have documented the physical health and health services use of Veterans in Canada, and thus there is limited evidence to inform public health policy and resource allocation. METHODS: In a retrospective, matched cohort of Veterans and the Ontario general population between 1990-2019, we used routinely collected provincial administrative health data to examine chronic disease prevalence and health service use. Veterans were defined as former members of the Canadian Armed Forces or RCMP. Crude and adjusted effect estimates, and 95% confidence limits were calculated using logistic regression (asthma, COPD, diabetes, myocardial infarction, rheumatoid arthritis, family physician, specialist, emergency department, and home care visits, as well as hospitalizations). Modified Poisson was used to estimate relative differences in the prevalence of hypertension. Poisson regression compares rates of health services use between the two groups. RESULTS: The study included 30,576 Veterans and 122,293 matched civilians. In the first five years after transition to civilian life, Veterans were less likely than the general population to experience asthma (RR 0.50, 95% CI 0.48-0.53), COPD (RR 0.32, 95% CI 0.29-0.36), hypertension (RR 0.74, 95% CI 0.71-0.76), diabetes (RR 0.71, 95% CI 0.67-0.76), myocardial infarction (RR 0.76, 95% CI 0.63-0.92), and rheumatoid arthritis (RR 0.74, 95% CI 0.60-0.92). Compared to the general population, Veterans had greater odds of visiting a primary care physician (OR 1.76, 95% CI 1.70-1.83) or specialist physician (OR 1.39, 95% CI 1.35-1.42) at least once in the five-year period and lower odds of visiting the emergency department (OR 0.95, 95% CI 0.92-0.97). Risks of hospitalization and of receiving home care services were similar in both groups. CONCLUSIONS: Despite a lower burden of comorbidities, Veterans had slightly higher physician visit rates. While these visits may reflect an underlying need for services, our findings suggest that Canadian Veterans have good access to primary and specialty health care. But in light of contradictory findings in other jurisdictions, the underlying reasons for our findings warrant further study.


Assuntos
Artrite Reumatoide , Asma , Hipertensão , Infarto do Miocárdio , Doença Pulmonar Obstrutiva Crônica , Veteranos , Artrite Reumatoide/epidemiologia , Asma/epidemiologia , Asma/terapia , Doença Crônica , Estudos de Coortes , Serviços de Saúde , Humanos , Ontário/epidemiologia , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Dados de Saúde Coletados Rotineiramente
10.
Sci Rep ; 12(1): 15367, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100660

RESUMO

In this study, we investigated the usefulness of FDG-PET/CT for predicting spontaneous regression in methotrexate-associated lymphoproliferative disorder (MTX-LPD). Twenty patients with rheumatoid arthritis who were diagnosed with MTX-LPD were enrolled in the study. These patients were divided into those who showed spontaneous regression (SR group: ten patients) and those who received chemotherapy after discontinuation of MTX (CTx group: ten patients). Between-group differences in potential biomarkers were compared, including clinical markers at the onset of LPD [serum LDH and interleukin 2 receptor (sIL-2R)], change in absolute number of peripheral lymphocytes (ΔALC) over follow-up, and the FDG-PET/CT-derived parameters of maximum standardized uptake value (SUVmax), mean SUV (SUVmean), peak SUV (SUVpeak), sum of the metabolic tumor volume (MTVsum), and sum of total lesion glycolysis (TLGsum). The levels of sIL-2R, MTVsum, and TLGsum were significantly lower in the SR group than in the CTx group. In addition, ΔALC was higher in the SR group. In conclusion, MTV and TLG values measured by FDG-PET/CT may be suitable for use as predictors of SR in patients with MTX-LPD.


Assuntos
Artrite Reumatoide , Transtornos Linfoproliferativos , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Fluordesoxiglucose F18/metabolismo , Humanos , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico por imagem , Metotrexato/efeitos adversos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos
11.
Drug Des Devel Ther ; 16: 3015-3022, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105319

RESUMO

Purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease with severe inflammatory responses. Dehydrozingerone (DHZ) is a potent bioactive compound found in the rhizomes of Zingiber officinale, and it has been reported as an excellent anti-inflammatory and antioxidant agent. This study evaluated the anti-arthritic effects of DHZ in complete Freund's adjuvant (CFA)-induced arthritis. Methods: CFA administered rats were intragastrically treated with DHZ (100 mg/kg) for 28 days, and arthritis severity was assessed via body weight, arthritic score, paw edema and hyperalgesia. Serum inflammation biomarkers, oxidative stress markers, inflammatory cytokines and liver function enzymes were evaluated. Results: The results indicated that DHZ significantly ameliorated arthritis severity as shown by reduced arthritic score, thymus and spleen indexes, paw circumference, paw withdrawal threshold and latency as well as increased body weight gain. Furthermore, DHZ treatment persuasively reduced serum levels of alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1ß and 6 (IL-1ß and IL-6), malondialdehyde (MDA), vascular endothelial growth factor (VEGF) and transforming growth factor ß (TGF-ß). In addition, DHZ observably increased serum superoxide dismutase (SOD) and glutathione (GSH) levels in treated rats. Conclusion: These findings suggest that DHZ possesses anti-RA effect properties via modulating the inflammatory responses and oxidative stress.


Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Peso Corporal , Adjuvante de Freund/efeitos adversos , Glutationa/metabolismo , Hiperalgesia , Interleucina-6/metabolismo , Estresse Oxidativo , Ratos , Estirenos , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Front Immunol ; 13: 980805, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091038

RESUMO

Observations from numerous clinical, epidemiological and serological studies link periodontitis with severity and progression of rheumatoid arthritis. The strong association is observed despite totally different aetiology of these two diseases, periodontitis being driven by dysbiotic microbial flora on the tooth surface below the gum line, while rheumatoid arthritis being the autoimmune disease powered by anti-citrullinated protein antibodies (ACPAs). Here we discuss genetic and environmental risk factors underlying development of both diseases with special emphasis on bacteria implicated in pathogenicity of periodontitis. Individual periodontal pathogens and their virulence factors are argued as potentially contributing to putative causative link between periodontal infection and initiation of a chain of events leading to breakdown of immunotolerance and development of ACPAs. In this respect peptidylarginine deiminase, an enzyme unique among prokaryotes for Porphyromonas gingivalis, is elaborated as a potential mechanistic link between this major periodontal pathogen and initiation of rheumatoid arthritis development.


Assuntos
Artrite Reumatoide , Periodontite , Anticorpos Anti-Proteína Citrulinada , Autoanticorpos , Humanos , Porphyromonas gingivalis , Desiminases de Arginina em Proteínas
13.
Pneumologie ; 76(9): 614-621, 2022 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-36104017

RESUMO

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is of high clinical relevance. It not only affects the quality of life but also makes a significant contribution to the mortality rate of patients with rheumatoid arthritis. RA-ILD can present with all known radiological and histopathological patterns seen in other interstitial pneumonias. Among these pneumonias, diffuse alveolar damage (DAD), followed by usual interstitial pneumonia (UIP) has the worst prognosis. In addition, acute exacerbation of RA-ILD, which can occur at any time during the disease, is highly lethal. An algorithm for the diagnosis and treatment of RA-ILD is pending and will be addressed in the following article. In addition to immunosuppressants and disease-modifying antirheumatic drugs (DMARD), antifibrotics have recently gained importance in the therapy of RA-ILD.


Assuntos
Artrite Reumatoide , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/terapia , Prognóstico , Qualidade de Vida
14.
Saudi Med J ; 43(9): 1062-1065, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36104053

RESUMO

Rheumatoid arthritis is a common autoimmune disease. Malignancy is a serious complication of rheumatoid arthritis and its treatment. In this article, we discuss a 61-year-old woman who is a known case of Rheumatoid arthritis and secondary Sjögren's syndrome treated with disease-modifying anti-rheumatoid drugs and multiple lines of biological therapies. She was found to have recto-sigmoid cancer, disseminated tuberculosis infection, and acute lymphoid leukemia at different intervals of treatment. Therefore, it is advisable to initiate appropriate screening programs that target high-risk people for malignancy.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Neoplasias , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias/complicações
15.
Int J Clin Pract ; 2022: 3406783, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101813

RESUMO

Background: Infliximab (IFX) biosimilar was the first biosimilar approved in Jordan in 2014, with limited evidence of its safety and effectiveness from the Middle East and North Africa (MENA) region. Thus, this study aimed to evaluate the safety and effectiveness of IFX biosimilar in active rheumatoid arthritis (RA) patients over 34 weeks by investigating (1) the adverse events (AEs), serious adverse events (SAEs), and therapy discontinuation and (2) the score changes of the 28-Joint Disease Activity Score (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ-DI). Methods: This multicenter prospective cohort study collected clinical parameters within hospital settings every four weeks. The numbers and percentages of observed AEs and SAEs were informed. The DAS28 utilizing Erythrocyte Sedimentation Rate (ESR), HAQ-DI, and ESR were reported at baseline and 14th and 30th weeks; thus, they were reported as means (SD). Results: A total of 22 RA patients were enrolled and initiated IFX biosimilar, of which nine (41.0%) discontinued the study, but their data were analyzed up to the point of withdrawal. A total of 35 AEs were reported in 14 patients, including two (5.7%) SAEs. None of the participants discontinued treatment due to AEs. The mean (SD) score of DAS28-ESR significantly decreased from 6.55 (1.16) at baseline to 4.59 (1.45) at week 14 (p < 0.0001) and to 4.77 (1.09) at week 30 (p < 0.0001). Similarly, the mean (SD) HAQ-DI score significantly decreased from 0.95 (0.74) at baseline to 0.48 (0.62) at week 14 (p=0.008) and to 0.71 (0.78) at week 30 (p=0.483). The mean (SD) value of ESR decreased from 58.75 (26.94) at baseline to 47.92 (33.89) at week 14 (p=0.082) and to 39.83 (17.38) at week 30 (p=0.005). Conclusion: IFX biosimilar demonstrated safety and effectiveness in managing RA patients bringing real-world clinical support for biosimilars' role in rheumatology.


Assuntos
Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/efeitos adversos , Humanos , Infliximab/efeitos adversos , Jordânia , Mitoxantrona/análogos & derivados , Estudos Prospectivos
16.
Reumatismo ; 74(2)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36101988

RESUMO

The purpose of this study was to compare and correlate disease activity score including 28 joints counts (DAS-28) Squeeze with DAS-28 and clinical disease activity index (CDAI) to assess disease activity (DA) in rheumatoid arthritis (RA) patients. A total of 100 RA patients were included in the study. All subjects were evaluated for disease activity using the DAS-28 Squeeze, DAS-28, and CDAI. Spearman's rho (ρ) was calculated to determine the correlation between DAS-28 Squeeze, DAS-28, and CDAI. Cross-tabulation was performed to compare and calculate the kappa coefficient for the link between two indices. For each scale, Cronbach's alpha was also calculated to test dependability. The average age of the study group was 43.9±11.3. The mean scores on the DAS-28 Squeeze, DAS-28, and CDAI were, respectively, 3.58±1.06, 5.06±1.56, and 22.81±14.92. p=0.001 indicated a significant correlation between DAS-28 Squeeze and DAS-28 (ρ=0.986) and CDAI (ρ=0.939) for DAS-28 Squeeze. There was a considerable correlation between all three measures at various DA levels. Cronbach's alpha for DAS-28 Squeeze, DAS-28, and CDAI were respectively 0.716, 0.663, and 0.734. DAS-28 Squeeze exhibited a substantial positive association with DAS-28 and CDAI for assessing disease activity and appears to be a more useful and reliable method than DAS-28 and CDAI for monitoring disease activity in RA patients.


Assuntos
Artrite Reumatoide , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/análogos & derivados , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Humanos , Índice de Gravidade de Doença
17.
Front Immunol ; 13: 940918, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052084

RESUMO

Background: Rheumatoid arthritis is a highly heterogeneous autoimmune disease characterized by unpredictable disease flares and significant differences in therapeutic response to available treatments. One possible reason for poor efficacy is that it cannot be treated accurately due to no optimal stratification for RA patients. Objective: This study aims to construct an RA classification model by m6A characters and further predict response to medication. Methods: Twenty m6A regulators were used to construct a random forest diagnosis model, and RNA-seq analysis was employed for external validation. The RNA modification patterns mediated by 20 m6A regulators were systematically evaluated in 1191 RA samples and explored different molecular clusters associated with other immune microenvironment characteristics and biological pathways. Then, we established an m6A score model to quantify the m6A modification patterns. The model was applied to patients at baseline to test the association between m6Ascore and infliximab responsiveness. Results: The m6A diagnosis model showed good discriminatory ability in distinguishing RA. Patients with RA were classified into three clusters with distinct molecular and cellular signatures. Cluster A displayed strongly activated inflammatory cells and pathways. Specific innate lymphocytes occupied cluster B. Cluster C was mainly enriched in prominent adaptive lymphocytes and NK-mediated cytotoxicity signatures with the highest m6A score. Patients with a low m6Ascore exhibited significantly infliximab therapeutic benefits compared with those with a high m6Ascore (p< 0.05). Conclusion: Our study is the first to provide a comprehensive analysis of m6A modifications in RA, which provides an innovative patient stratification framework and potentially enables improved therapeutic decisions.


Assuntos
Adenosina , Artrite Reumatoide , Adenosina/metabolismo , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Humanos , Infliximab/uso terapêutico , RNA/genética , RNA-Seq
18.
Biomed Pharmacother ; 154: 113614, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36058148

RESUMO

Rheumatoid arthritis (RA) is a chronic multifactorial disorder of autoimmune etiology with a complex pathophysiological mechanism that is not yet fully elucidated. RA pharmacotherapy includes active molecules of chemical or biological nature that offer symptomatic relief and a slowing of progression, but still in a context of incurability. Therefore, the development of continuous research and multidisciplinary collaboration is essential. Although the management of RA is a topic of significant scientific relevance, existing bibliometric analyses are insufficient to assess this vast field. Consequently, the present study examines numerous manuscripts indexed in the Web of Science database using the VOSviewer software to provide through statistical interpretation of the data a comprehensive description of RA pharmacotherapy in terms of scientific impact, current state of research, number and frequency of citations, most prolific journals, authors, and countries, along with their relationships and other useful data for the literature search/publication process. Furthermore, the use of bubble maps of term occurrence has applicability in identifying current research trends in the field of RA pharmacotherapy as well as their evolution over the years. The leader in this field in terms of published papers is the United States, and the most prolific journal is Annals of the rheumatic diseases. The global management of RA, which is characterized by extensiveness and depth due to many variables, suggests the need for a conceptual framework based on pharmacotherapy coupled with comprehensive bibliometric studies, and the results may be useful for researchers in setting specific objectives that contribute to improving RA outcomes.


Assuntos
Artrite Reumatoide , Bibliometria , Artrite Reumatoide/tratamento farmacológico , Bases de Dados Factuais , Humanos
19.
Front Immunol ; 13: 901555, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059477

RESUMO

Background: Pyruvate kinase M2 (PKM2) is an enzyme that regulates the final process of glycolysis and exists in tetrameric and dimeric forms. The dimeric form of PKM2, also known as tumour M2-PK, increases when aerobic glycolysis is augmented, a feature observed in rheumatoid arthritis (RA). We investigated whether plasma tumour M2-PK is elevated in patients with RA and whether its levels correlate with disease activity. Methods: Plasma levels of tumour M2-PK were measured for patients with RA (n=151), those with osteoarthritis (OA) (n=37), and controls (n=37). We evaluated the association between plasma tumour M2-PK and continuous variables using Pearson's correlation analysis, and multivariate logistic regression analysis to determine the association between plasma tumour M2-PK and disease activity status. Knee synovial tissue blocks from patients with RA and OA were subjected to real-time quantitative PCR (qPCR) using two different primers for PKM2 and tumour M2-PK immunohistochemical (IHC) staining. Results: The tumour M2-PK level significantly correlated with the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) (r=0.546, p<0.001) and DAS28-C-reactive protein (CRP) (r=0.589, p<0.001). Moreover, repeat testing of tumour M2-PK levels in 20 patients revealed a significant decline in tumour M2-PK levels after reduction in inflammation (p<0.001). Area under the receiver operating characteristic curve (AUROC) analysis demonstrated that upon incorporation of tumour M2-PK, ESR, and CRP, the area under the curve was 0.962 for distinguishing moderate/high from remission/low disease activity. Adjusted logistic regression also revealed that a tumour M2-PK >43.9 U/mL (OR 3.672, p=0.042) independently predicted moderate/high disease activity status. Furthermore, tumour M2-PK levels in patients with RA were significantly higher than in those with OA and controls (all p<0.001). However, no differences were found in PKM2 expression in RA and OA synovial tissues as assessed by qPCR, and IHC analysis revealed negligible tumour M2-PK expression in the synovial tissues. Conclusion: Circulating plasma tumour M2-PK levels may be a clinically useful indicator for evaluating disease activity and RA diagnosis.


Assuntos
Artrite Reumatoide , Osteoartrite , Piruvato Quinase , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/patologia , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Humanos , Neoplasias/diagnóstico , Neoplasias/patologia , Osteoartrite/diagnóstico , Osteoartrite/metabolismo , Osteoartrite/patologia , Membrana Sinovial/patologia
20.
Int J Mol Sci ; 23(17)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36076933

RESUMO

Epidemiologic studies have shown associations between periodontitis and rheumatoid arthritis (RA), but a causal relationship has not been established. Citrullination of gingival proteins by human peptidylarginine deiminases (PADs) or PAD from Porphyromonas gingivalis has been proposed to generate autoantigens in anti-CCP-positive RA. This study investigated whether the association between periodontitis and RA is influenced by single nucleotide polymorphisms (SNPs) in the genes encoding PAD2 and PAD4 that catalyze aberrant citrullination in RA and often are overexpressed in inflamed gingival connective tissue in subjects with periodontitis. The study included 137 RA patients and 161 controls with self-reported periodontitis. Periodontitis onset preceded RA onset by 13 years on average and was not associated with any of the SNPs investigated. In subjects with periodontitis, carriage of the minor alleles of rs2057094 and rs2235912 in PADI2 significantly increased the risk of RA (odds ratios 1.42 [p = 0.03] and 1.48 [p = 0.02], respectively), and this effect was driven by the anti-CCP-negative RA patients. The minor alleles of these SNPs only increased risk of anti-CCP-positive RA in individuals with periodontitis and a history of smoking. These data suggest that individuals with periodontitis carrying the minor alleles of SNPs rs2057094, rs2076616 and rs2235912 in PADI2 may be at increased risk of RA.


Assuntos
Artrite Reumatoide , Periodontite , Anticorpos Anti-Proteína Citrulinada , Artrite Reumatoide/complicações , Artrite Reumatoide/genética , Autoanticorpos , Humanos , Hidrolases/genética , Hidrolases/metabolismo , Periodontite/complicações , Periodontite/genética , Polimorfismo de Nucleotídeo Único , Desiminases de Arginina em Proteínas/genética , Desiminases de Arginina em Proteínas/metabolismo
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