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OBJECTIVE: To report pharmacokinetics (PK), immunogenicity, clinical effect, and safety of intravenous (IV) golimumab in children with active polyarticular-course juvenile idiopathic arthritis (pcJIA) who participated in A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy (GO-VIVA)'s open-label, long-term extension (LTE) through week 252. METHODS: GO-VIVA participants who continued IV golimumab (80 mg/m2 every 8 weeks) after week 52 were included. PK and safety were assessed through week 244 (last dose) and week 252, respectively, and clinical response through week 116. Clinical outcomes included JIA-American College of Rheumatology (ACR) responses and clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10). Binary outcomes used nonresponder imputation, and other descriptive analyses used observed data. RESULTS: Of 112/127 (88.2%) participants entering the LTE, 69 completed the week 252 visit. Median steady-state trough golimumab concentrations were generally maintained from week 52 through week 244 (range 0.3-0.6 µg/mL). Antigolimumab antibody rates were consistent through week 52 (39.2% [49/125]) and week 244 (44.8% [56/125]). Week 52 JIA-ACR 30/50/70/90 response rates (75.6% [96/127], 74% [94/127], 65.4% [83/127], and 48.8% [62/127], respectively) were generally maintained through week 116 (72.4% [92/127], 71.7% [91/127], 63.8% [81/127], and 50.4% [64/127], respectively), when the median cJADAS10 was 1.6 and 56.7% (72/127) of participants achieved cJADAS10 ≤ 5 (minimal disease activity). Rates (per 100 patient-years) of serious adverse events and serious infections through week 252 were 7.7 and 3.9, respectively. CONCLUSION: GO-VIVA LTE participants experienced adequate PK exposure and stable safety and immunogenicity. The majority of participants experienced no more than minimal residual disease activity. Data suggest IV golimumab treatment provided durable clinical response through week 116, with an acceptable risk-benefit profile.
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PURPOSE: To compare the diversities and abundances of bacterial taxa in the microbiome of patients with HLA B27-positive acute anterior uveitis (AAU) in the active and inactive phases. METHODS: An observational descriptive prospective and comparative study was conducted in ten HLA-B27-positive AAU patients (44.6 ± 13.4 years). The microbiome of the stool samples obtained in the active and inactive stages was analyzed by sequencing the V3 region of the 16S rRNA gene. RESULTS: The differences in the bacteria profile between active and inactive stages in each individual were confirmed (p < 0.0001). Ten OTUs were found exclusively in the active phase of 90% of the individuals, suggesting a proinflammatory association. Blautia OUT_4 and Faecalibacterium OUT_2 abundances showed a direct relationship between abundance and severity of ocular inflammation. Two OTUs were exclusive of the inactive stage, suggesting an anti-inflammatory role. CONCLUSION: The metagenomic profile of the fecal microbiota differs in the acute phase of the AAU compared to when the inflammation subsides, despite being the same individual and a short time-lapse. AAU is a fertile field for studying the connection between subtle rapid changes in microbiota and their systemic consequences.
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To compare the demographic, clinical, and laboratory characteristics, disease onset, and clinical features of radiographic axial Spondyloarthritis (r-axSpA) and non-radiographic axial Spondyloarthritis (nr-axSpA) patients. All patients who attended outpatient spondylarthritis (SpA) clinics at Hospital General de Mexico and the Instituto Nacional de la Nutrición from 1998 to 2005 and met the rheumatologist diagnostic criteria for SpA were selected. Then the SpA patients were classified by European Spondyloarthropathy Study Group criteria (ESSG). We selected SpA patients with axial presentation as axial SpA (axSpA), and they were classified as r-axSpA if they met modified New York (mNY) criteria for sacroiliitis and as nr-axSpA if they did not meet mNY criteria; to compared clinical, demographic, and laboratory test between the subgroups. It included 148 SpA patients; 55 (37.2%) patients had r-axSpA, and 70 (47.3%) had nr-axSpA. The nr-axSpA patients had a lower proportion of males (58.6% vs 78.2%, P < 0.05), lower HLA-B27 frequency (54.3%. vs. 92.7%, P < 0.05), were older at disease onset (21 vs 16 years; P < 0.01) and had a higher frequency of infections at disease onset (9.1% vs 32.9, P < 0.05) than r-axSpA. BASFI (2.9 vs 4.8; P < 0.0001), Dougados functional index (7 vs. 14; P < 0.05), and BASDAI (4.1 vs. 5.2; P < 0.001) were lower in patients with nr-axSpA than r-axSpA, respectively. The factors that most influenced the presentation of r-axSpA were history of uveitis (OR 14, 95% CI 2.3-85), HLA-B27 (OR 7.97, 95% CI, 2.96-122), male sex (OR 6.16, 95% CI, 1.47-25.7), axial enthesopathy count (OR 1.17 95% CI, 1.03-1.33). This study provides insight into the differences between nr-axSpA and r-axSpA in Mexico. Patients with r-axSpA were mainly male, with a younger presentation age, a higher prevalence of HLA-B27, more history of uveitis, fewer episodes of dactylitis, more axial enthesopathy, and higher disease activity than nr-axSpA.
Subject(s)
Axial Spondyloarthritis , Humans , Male , Mexico/epidemiology , Female , Adult , Axial Spondyloarthritis/diagnostic imaging , HLA-B27 Antigen , Radiography/methods , Middle Aged , Cohort Studies , Young Adult , Spondylarthritis/diagnostic imagingABSTRACT
OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Arthritis, Rheumatoid/drug therapy , Humans , Mexico , Antirheumatic Agents/therapeutic use , Glucocorticoids/therapeutic use , Female , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Pregnancy , Analgesics/therapeutic useABSTRACT
Desarrollar guías actualizadas para el manejo farmacológico de la artritis reumatoide (AR). Se conformó un grupo de expertos que fueran representativos de las distintas regiones geográficas y los diferentes servicios médicos que atienden a la población mexicana con AR. Se desarrollaron preguntas basadas en Población, Intervención, Comparación y Desenlace [Outcome] (PICO) que fueron consideradas relevantes desde el punto de vista clínico; las preguntas encontraron su respuesta en los resultados de una revisión sistemática de la literatura (RSL) reciente y la validez de la evidencia fue evaluada mediante el sistema GRADE, considerado un estándar para estos fines. Posteriormente, el grupo de expertos desarrollaró un acuerdo en la dirección y fuerza de las recomendaciones mediante un proceso de votación en distintas etapas. Las guías actualizadas para el tratamiento de la AR categorizan en forma estratificada a las distintas opciones terapéuticas incluyendo las distintas familias de fármacos modificadores de la enfermedad (FARME): convencionales, biológicos e inhibidores de JAK), además de AINE, glucocorticoides y analgésicos. Establece por consenso el uso de todos ellos en distintas subpoblaciones de interés de pacientes con AR, y aborda, además, aspectos relacionados con la vacunación, la COVID-19, la cirugía, el embarazo y la lactancia entre otros. La presente actualización de las guías mexicanas para el tratamiento farmacológico de la AR brinda elementos de referencia en la toma de decisiones basados en la evidencia científica más reciente, y recomienda la participación del paciente para la toma de decisiones conjuntas en la búsqueda del mayor beneficio de nuestros pacientes; establece además, recomendaciones para el manejo de una diversidad de condiciones relevantes que afectan a nuestros pacientes.
Subject(s)
Humans , Arthritis, Rheumatoid/drug therapy , Biological Therapy , Antirheumatic Agents/therapeutic use , MexicoABSTRACT
OBJECTIVE: Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries. METHODS: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries. RESULTS: Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA. CONCLUSION: Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients.
Subject(s)
Antirheumatic Agents , Arthritis, Psoriatic , Rheumatology , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/therapy , Humans , Antirheumatic Agents/therapeutic use , Rheumatology/standards , Societies, Medical , Latin America , Evidence-Based Medicine , Quality of Life , Anti-Inflammatory Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic useABSTRACT
OBJECTIVE: To describe characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Argentina, Mexico and Brazil, and to assess factors associated with mortality in this population. METHODS: Data from 3 national registries, SAR-COVID (Argentina), CMR-COVID (Mexico), and ReumaCoV-Brasil (Brazil), were combined. Adult patients with IMIDs and SARS-CoV-2 infection were recruited. Sociodemographic data, comorbidities, IMID clinical characteristics and treatment, and SARS-CoV-2 infection presentation and outcomes were recorded. RESULTS: A total of 4827 individuals were included: 2542 (52.7%) from SAR-COVID, 1167 (24.2%) from CMR-COVID, and 1118 (23.1%) from ReumaCoV-Brasil. Overall, 82.1% were female with a mean age of 49.7 (SD, 14.3) years; 22.7% of the patients were hospitalized, and 5.3% died because of COVID-19 (coronavirus disease 2019). Argentina and Brazil had both 4% of mortality and Mexico 9.4%. In the multivariable analysis, older age (≥60 years; odds ratio [OR], 7.4; 95% confidence interval [CI], 4.6-12.4), male sex (OR, 1.5; 95% CI, 1.1-2.1), living in Mexico (OR, 3.0; 95% CI, 2.0-4.4), comorbidity count (1 comorbidity: OR, 1.5; 95% CI, 1.0-2.1), diagnosis of connective tissue disease or vasculitis (OR, 1.8; 95% CI, 1.3-2.4), and other diseases (OR, 2.6; 95% CI, 1.6-4.1) compared with inflammatory joint disease, high disease activity (OR, 4.2; 95% CI, 2.5-7.0), and treatment with glucocorticoids (OR, 1.9; 95% CI, 1.4-2.5) or rituximab (OR, 4.2; 95% CI, 2.7-6.6) were associated with mortality. CONCLUSIONS: Mortality in patients with IMIDs was particularly high in Mexicans. Ethnic, environmental, societal factors, and different COVID-19 mitigation measures adopted have probably influenced these results.
Subject(s)
COVID-19 , Rheumatic Diseases , Adult , Humans , Male , Female , Middle Aged , SARS-CoV-2 , Mexico/epidemiology , Latin America , Argentina/epidemiology , Brazil/epidemiology , Rheumatic Diseases/epidemiology , Immunomodulating AgentsABSTRACT
Axial spondyloarthritis (axSpA) comprises a spectrum of chronic inflammatory manifestations affecting the axial skeleton and represents a challenge for diagnosis and treatment. Our objective was to generate a set of evidence-based recommendations for the management of axSpA for physicians, health professionals, rheumatologists and policy decision makers in Pan American League of Associations for Rheumatology (PANLAR) countries. Grading of Recommendations, Assessment, Development and Evaluation-ADOLOPMENT methodology was used to adapt existing recommendations after performing an independent systematic search and synthesis of the literature to update the evidence. A working group consisting of rheumatologists, epidemiologists and patient representatives from countries within the Americas prioritized 13 topics relevant to the context of these countries for the management of axSpA. This Evidence-Based Guideline article reports 13 recommendations addressing therapeutic targets, the use of NSAIDs and glucocorticoids, treatment with DMARDs (including conventional synthetic, biologic and targeted synthetic DMARDs), therapeutic failure, optimization of the use of biologic DMARDs, the use of drugs for extra-musculoskeletal manifestations of axSpA, non-pharmacological interventions and the follow-up of patients with axSpA.
Subject(s)
Antirheumatic Agents , Axial Spondyloarthritis , Biological Products , Rheumatology , Spondylarthritis , Spondylitis, Ankylosing , Humans , Antirheumatic Agents/therapeutic use , Biological Products/therapeutic use , Spondylarthritis/diagnosis , Spondylarthritis/drug therapyABSTRACT
The attitudes toward emerging COVID-19 vaccines have been of great interest worldwide, especially among vulnerable populations such as patients with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to analyze the relationship between the nationwide number of COVID-19 cases and deaths, and vaccine acceptance or hesitancy of patients with RMDs from four patient care centers in Mexico. Furthermore, we explored differences in acceptance according to specific diagnoses: rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This ecological study was a secondary analysis of a cross-sectional study using a validated questionnaire to measure vaccine acceptance. We generated a global Likert scale to evaluate overall attitudes toward the COVID-19 vaccine. We analyzed data from 1336 patients from March to September 2021: 85.13% (1169) were women, with a mean age of 47.87 (SD 14.14) years. The most frequent diagnoses were RA (42.85%, 559) and SLE (27.08%, 393). 635(47.52%) patients were unvaccinated, 253(18.93%) had one dose and 478(35.77%) had two doses. Of all participating patients, 94% were accepting toward the COVID-19 vaccine. Vaccine acceptance remained consistently high throughout the study. However, differences in vaccine acceptance are identified when comparing diagnoses. The peak of the national epidemic curve coincided with an increase in hesitancy among patients with RA. Contrastingly, patients with SLE became more accepting as the epidemic curve peaked. Mexican patients show high acceptance of the COVID-19 vaccine, influenced in part by a patient's specific diagnosis. Furthermore, vaccine acceptance increased mirroring the curve of COVID-19 cases and deaths in the country. This should be taken into consideration when updating recommendations for clinical practice.
Subject(s)
Arthritis, Rheumatoid , COVID-19 , Lupus Erythematosus, Systemic , Rheumatic Diseases , Vaccines , Humans , Female , Middle Aged , Male , COVID-19 Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Rheumatic Diseases/epidemiology , Arthritis, Rheumatoid/epidemiology , Lupus Erythematosus, Systemic/epidemiology , VaccinationABSTRACT
OBJECTIVE: Describe the distribution of adult and pediatric rheumatologists with current certification in Mexico and the factors associated with this distribution. METHODS: The databases of the Mexican Council of Rheumatology and the Mexican College of Rheumatology for 2020 were reviewed. The rate of rheumatologists per 100,000 inhabitants by state of the Mexican Republic was calculated. To find out the number of inhabitants by state, the results of the 2020 population census of the National Institute of Statistics and Geography were consulted. The number of rheumatologists with current certification by state, age, and sex was analyzed. RESULTS: In Mexico, there are 1002 registered adult rheumatologists with a mean age of 48.12⯱â¯13 years. The male gender prevailed with a ratio of 1.18:1. Ninety-four pediatric rheumatologists were identified with a mean age of 42.25⯱â¯10.4 years, with a predominance of the female gender with a ratio of 2.2:1. In Mexico City and Jalisco, more than one rheumatologist/100,000 inhabitants were reported in the specialty of adults and only in Mexico City in pediatrics. The current certification is 65%-70% on average and the factors associated with a higher prevalence were younger age, female gender and geographic location. CONCLUSIONS: There is a shortage of rheumatologists in Mexico and in the pediatric area there are underserved regions. It is important that health policies apply measures that allow a more balanced and efficient regionalization of this specialty. Although most rheumatologists have current certification, it is necessary to establish strategies to increase this proportion.
Subject(s)
Rheumatologists , Rheumatology , Adult , Humans , Male , Female , Child , Middle Aged , Mexico , Certification , Databases, FactualABSTRACT
Porphyromonas gingivalis secretes virulence factors like Arg-gingipains and peptidyl arginine deiminase (PPAD), that are associated with rheumatoid arthritis (RA) pathogenesis. However, there is no information regarding the antibody titers for these bacterial enzymes as systemic indicators or biomarkers in RA. In this cross-sectional study, 255 individuals were evaluated: 143 were diagnosed with RA, and 112 were without RA. Logistic regression models adjusted for age, sex, basal metabolic index, smoking, and periodontitis severity were used to evaluate the association of RA with rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs), erythrocyte sedimentation rate, high sensitivity C-reactive protein, anti-RgpA, anti-PPAD, and double positive anti-RgpA/anti-PPAD. It was found that RF (odds ratio [OR] 10.6; 95% confidence interval [CI] 4.4-25), ACPAs (OR 13.7; 95% CI 5.1-35), and anti-RgpA/anti-PPAD double positivity (OR 6.63; 95% CI 1.61-27) were associated with RA diagnoses. Anti-RgpA was also associated with RA (OR 4.09; 95% CI 1.2-13.9). The combination of anti-RgpA/anti-PPAD showed a high specificity of 93.7% and 82.5% PPV in identifying individuals with RA. RgpA antibodies were associated with the periodontal inflammatory index in RA individuals (p < 0.05). The double positivity of the anti-RgpA/anti-PPAD antibodies enhanced the diagnosis of RA. Therefore, RgpA antibodies and anti-RgpA/anti-PPAD may be biomarkers for RA.
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PURPOSE: To analyze the differential transcriptome expression in hypertrophic ligaments flavum (HLF) compared to normal ligaments. METHODS: A case-control study was conducted that included 15 patients with hypertrophy of LF and 15 controls. Samples of LF were obtained through a lumbar laminectomy and analyzed by DNA microarrays and histology. The dysregulated biological processes, signaling pathways, and pathological markers in the HLF were identified using bioinformatics tools. RESULTS: The HLF had notable histological alterations, including hyalinosis, leukocyte infiltration, and disarrangement of collagen fibers. Transcriptomic analysis showed that up-regulated genes were associated with the signaling pathways of Rho GTPases, receptor tyrosine kinases (RTK), fibroblast growth factors (FGF), WNT, vascular endothelial growth factor, phosphoinositide 3-kinase (PIK3), mitogen-activated protein kinases, and immune system. The genes PIK3R1, RHOA, RPS27A, CDC42, VAV1, and FGF5, 9, 18, and 19 were highlighted as crucial markers in HLF. The down-expressed genes in the HLF had associations with the metabolism of RNA and proteins. CONCLUSION: Our results suggest that abnormal processes in hypertrophied LF are mediated by the interaction of the Rho GTPase, RTK, and PI3K pathways, which have not been previously described in the HLF, but for which there are currently therapeutic proposals. More studies are required to confirm the therapeutic potential of the pathways and mediators described in our results.
Subject(s)
Ligamentum Flavum , Spinal Stenosis , Humans , Phosphatidylinositol 3-Kinase/metabolism , Transcriptome , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Case-Control Studies , Ligamentum Flavum/pathology , rho GTP-Binding Proteins/metabolism , Vascular Endothelial Growth Factor A/metabolism , Fibroblast Growth Factors/metabolism , Hypertrophy/metabolism , Spinal Stenosis/pathology , Lumbar Vertebrae/pathologyABSTRACT
BACKGROUND: CrossFit is known as a functional fitness training high-intensity exercise to improve physical performance. The most studied polymorphisms are the ACTN3 R577X gene, known for speed, power, and strength, and ACE I/D, related to endurance and strength. The present investigation analyzed the effects of training on ACTN3 and ACE gene expression in CrossFit athletes for 12 weeks. METHODS: the studies included 18 athletes from the Rx category, where ACTN3 (RR, RX, XX) and ACE (II, ID, DD) characterization of genotypes and tests of maximum strength (NSCA), power (T-Force), and aerobic endurance (Course Navette) were performed. The technique used was the reverse transcription-quantitative PCR real-time polymerase chain reaction (RT-qPCR) for the relative expression analysis. RESULTS: the relative quantification (RQ) values for the ACTN3 gene increased their levels 2.3 times (p = 0.035), and for ACE, they increased 3.0 times (p = 0.049). CONCLUSIONS: there is an overexpression of the ACTN3 and ACE genes due to the effect of training for 12 weeks. Additionally, the correlation of the expression of the ACTN3 (p = 0.040) and ACE (p = 0.030) genes with power was verified.
Subject(s)
Exercise , Polymorphism, Genetic , Humans , Actinin/genetics , Athletes , Genotype , Peptidyl-Dipeptidase A/genetics , PrevalenceABSTRACT
Lifestyle modifications in preclinical Rheumatoid Arthritis (RA) could delay the ongoing pathogenic immune processes and potentially prevent its onset. Physical exercise (PE) benefits RA patients; however, its impact in reducing the risk of developing RA has scarcely been studied. The objective was to describe the effects of low-intensity PE applied at the disease's preclinical phase on the joints of DBA/1 mice with collagen-induced arthritis (CIA). Twelve mice with CIA were randomly distributed into two groups: the CIA-Ex group, which undertook treadmill PE, and the CIA-NoEx, which was not exercised. The effects of PE were evaluated through clinical, histological, transcriptomics, and immunodetection analyses in the mice's hind paws. The CIA-Ex group showed lower joint inflammation and damage and a decreased expression of RA-related genes (Tnf Il2, Il10, Il12a, IL23a, and Tgfb1) and signaling pathways (Cytokines, Chemokines, JAK-STAT, MAPK, NF-kappa B, TNF, and TGF-beta). TNF-α expression was decreased by PE in the inflamed joints. Low-intensity PE in pre-arthritic CIA reduced the severity through joint down-expression of proinflammatory genes and proteins. Knowledge on the underlying mechanisms of PE in preclinical arthritis and its impact on reducing the risk of developing RA is still needed.
Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Mice , Animals , Disease Models, Animal , Mice, Inbred DBA , Arthritis, Rheumatoid/metabolism , Inflammation , Cytokines/metabolism , ExerciseABSTRACT
The fibroblast-like synoviocytes (FLS) have a crucial role in the pathogenesis of Rheumatoid Arthritis (RA); however, its precise mechanisms remain partially unknown. The involvement of the fibroblast in activating adjuvant-induced arthritis (AA) has not been previously reported. The objective was to describe the participation of footpads' fibroblasts in the critical initial process that drives the AA onset. Wistar rats were injected with Complete Freund's Adjuvant (CFA) or saline solution in the hind paws' footpads and euthanized at 24 or 48 h for genetic and histological analyses. Microarrays revealed the differentially expressed genes between the groups. The CFA dysregulated RA-linked biological processes at both times. Genes of MAPK, Jak-STAT, HIF, PI3K-Akt, TLR, TNF, and NF-κB signaling pathways were altered 24 h before the arrival of immune cells (CD4, CD8, and CD68). Key markers TNF-α, IL-1ß, IL-6, NFκB, MEK-1, JAK3, Enolase, and VEGF were immunodetected in fibroblast in CFA-injected footpads at 24 h but not in the control group. Moreover, fibroblasts in the CFA inoculation site overexpressed cadherin-11, which is linked to the migration and invasion ability of RA-FLS. Our study shows that CFA induced a pathological phenotype in the fibroblast of the inoculation site at very early AA stages from 24 h, suggesting a prominent role in arthritis activation processes.
Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Synoviocytes , Rats , Animals , Synoviocytes/metabolism , Synovial Membrane/pathology , Freund's Adjuvant , Phosphatidylinositol 3-Kinases/metabolism , Rats, Wistar , Arthritis, Experimental/metabolism , NF-kappa B/metabolism , Fibroblasts/metabolismABSTRACT
Adipokines are associated with the pathogenesis of rheumatoid arthritis (RA) and are potential biomarkers of disease activity, periodontitis, and obesity. The aim of this was to establish the association between adipokine profile, RA disease activity, body mass index, and periodontal infection. This study evaluated 51 patients with early-RA and 51 controls including serum rheumatological markers, adipokine levels, detection of Porphyromonas gingivalis and serum anti-Porphyromonas gingivalis antibodies, clinical and periodontal measurements. Statistical analyses were run with SPSS® V26, with a logistic regression model to confirm associations. The results show high levels of leptin were more frequent in patients (p = 0.001) who simultaneously showed a higher frequency of Porphyromonas gingivalis (p = 0.004). Patients with concomitant presence of Porphyromonas gingivalis, high clinical activity score, and overweight were correlated with high levels of leptin (OR, 7.20; 95% CI, 2.68-19.33; p = 0.0001) and adipsin (OR, 2.69; 95% CI, 1.00-7.28; p = 0.005). The conclusion is that high levels of leptin and adipsin are associated with greater clinical activity in early-RA patients with overweight and periodontal infection, whereby overweight and Porphyromonas gingivalis may enhance RA activity. This may represent a pathological mechanism between these conditions, where adipokines seem to have a key role.
ABSTRACT
To analyze the effect of levofloxacin-induced intestinal microbiota modifications on intestinal, joint, and systemic inflammation in the DBA/1 mice with spontaneous arthritis. The study included two groups of mice, one of which received levofloxacin. The composition and structure of the microbiota were determined in the mice's stool using 16S rRNA sequencing; the differential taxa and metabolic pathway between mice treated with levofloxacin and control mice were also defied. The effect of levofloxacin was evaluated in the intestines, hind paws, and spines of mice through DNA microarray transcriptome and histopathological analyses; systemic inflammation was measured by flow cytometry. Levofloxacin decreased the pro-inflammatory bacteria, including Prevotellaceae, Odoribacter, and Blautia, and increased the anti-inflammatory Muribaculaceae in mice's stool. Histological analysis confirmed the intestinal inflammation in control mice, while in levofloxacin-treated mice, inflammation was reduced; in the hind paws and spines, levofloxacin also decreased the inflammation. Microarray showed the downregulation of genes and signaling pathways relevant in spondyloarthritis, including several cytokines and chemokines. Levofloxacin-treated mice showed differential transcriptomic profiles between peripheral and axial joints and intestines. Levofloxacin decreased the expression of TNF-α, IL-23a, and JAK3 in the three tissues, but IL-17 behaved differently in the intestine and the joints. Serum TNF-α was also reduced in levofloxacin-treated mice. Our results suggest that the microbiota modification aimed at reducing pro-inflammatory and increasing anti-inflammatory bacteria could potentially be a coadjuvant in treating inflammatory arthropathies.
Subject(s)
Levofloxacin , Spondylarthritis , Mice , Animals , Levofloxacin/pharmacology , Transcriptome , Tumor Necrosis Factor-alpha/genetics , Dysbiosis/microbiology , RNA, Ribosomal, 16S/genetics , Mice, Inbred DBA , Inflammation/drug therapy , Inflammation/genetics , Inflammation/pathology , Mice, Inbred C57BLABSTRACT
There is little literature on the implementation of screening criteria for inflammatory bowel disease (IBD) in patients with spondyloarthritis (SpA). This study aimed to apply IBD screening criteria in a group of patients with SpA without IBD diagnosis and correlate them to endoscopic findings and disease activity. A total of 82 patients with SpA were included. The IBD screening test and ileocolonoscopy with digital chromoendoscopy with magnification and histological analysis were performed. The data were analysed with Chi-square test/Fisher's exact test and multiple correspondence analysis. The major screening criteria found in 48.7% of the patients were associated with a history of infection (p = 0.037). Rectal bleeding was associated with the diagnosis of ankylosing spondylitis, acute inflammation, enthesitis and tissue architecture alteration in the ileum (p < 0.050). Diarrhoea was associated with a higher disease activity score (p = 0.02). Minor screening criteria were associated with painful inflammatory joint (p = 0.05), high disease activity score (p = 0.001) and high calprotectin levels (p = 0.050). Abdominal pain (36.9%) was associated with axial/peripheral compromise (p = 0.017), inflammatory back pain (p = 0.01), enthesitis (p = 0.021), higher disease activity score (p = 0.023) and acute ileum inflammation (p = 0.046). Diarrhoea of 4 weeks and abdominal pain were the most prevalent major and minor screening criteria, respectively, being related to early manifestations of inflammatory bowel compromise and higher disease activity score. This screening test grants a chance of opportune referral of SpA patients from rheumatology to gastroenterology.
Subject(s)
Inflammatory Bowel Diseases , Spondylarthritis , Spondylitis, Ankylosing , Humans , Spondylarthritis/complications , Spondylarthritis/diagnosis , Inflammatory Bowel Diseases/complications , Spondylitis, Ankylosing/complications , Spondylitis, Ankylosing/diagnosis , Diarrhea , Abdominal Pain , Inflammation/complicationsABSTRACT
BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation and destruction. OBJECTIVE: Establish the association between Porphyromonas gingivalis (P. gingivalis) infection, body mass index (BMI), joint involvement, and serum adipokines in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA). METHODS: The cross-sectional study evaluated 124 FDR and 124 healthy controls (HC). The clinical examination included joint and radiographic evaluation and calculation of BMI. Serum adipokine levels were measured (leptin, vaspin, adiponectin, resistin, and adipsin), as were the erythrocyte sedimentation rate, C-reactive protein, and anti-citrullinated protein antibodies. Investigations were performed to detect P. gingivalis, and anti-P. gingivalis antibodies. Statistical analyses were performed to confirm associations. RESULTS: Leptin levels in FDR were associated with BMI >25 (OR, 2.64; 95%CI, 1.17-5.97; P=0.019), radiographic damage (Simple Erosion Narrowing Score [SENS])/hands, total SENS, and joint space narrowing in feet (P=0.037, 0.026, 0.020, respectively). FDR had more tender joints (P=0.018); this finding was associated with high levels of leptin and resistin and low levels of adipsin (P=0.040, 0.040, and 0.019, respectively). The presence of P. gingivalis was related to FDR, low levels of adipsin, resistin, adiponectin, and a trend toward higher levels of leptin (P=0.002, 0.001, 0.003, and 0.060, respectively), whereas anti-P. gingivalis antibodies were related to low levels of adipsin (P=0.001). CONCLUSION: In FDR, serum adipokine levels were associated with overweight and the presence of P. gingivalis. Adipokine levels were also associated with joint involvement. Hence, adipokines may be involved in the pathogenesis of RA in FDR and warrant further investigation.
Subject(s)
Arthritis, Rheumatoid , Periodontal Diseases , Humans , Adipokines , Leptin , Resistin , Complement Factor D , Adiponectin , Cross-Sectional StudiesABSTRACT
BACKGROUND AND AIMS: Spondyloarthritis (SpA) is a group of autoinflammatory disorders, of which the primary extra-articular manifestation is inflammatory bowel disease (IBD). The oral cavity being a part of gastrointestinal tract, is significantly compromised in IBD, and in many cases, it is the first site of clinical manifestations of IBD. This study aimed to identify changes in the oral mucosa associated with the onset of IBD and their association with endoscopic/histological findings. MATERIALS AND METHODS: The study assessed 80 patients with SpA and 52 healthy controls. Oral, rheumatological, and gastroenterological assessments were performed. The ileocolonoscopy was performed via digital magnification chromoendoscopy. The statistical analysis consisted of Chi-square, Fisher's exact, and multiple correspondence discriminant analysis tests. RESULTS: From the disease cohort, 63.0% patients showed oral lesions (p = 0.050). These manifestations ranged from gingivitis (55.0%, p = 0.001), aphthous stomatitis (3.8%, p = 0.091), angular cheilitis (2.6%, p = 0.200), and perioral erythema with scaling (1.3%, p = 0.300). All patients who presented with alterations in colonic mucosa also had oral lesions associated with IBD (p = 0.039), specifically gingivitis/aphthous stomatitis (p = 0.029). CONCLUSION: The patients with SpA without IBD present significant oral signs and symptoms. Gingivitis seems to be the most relevant because of its associations with early endoscopic and histological findings. CLINICAL RELEVANCE: An integral approach to the diagnostic tests that includes evaluations of oral, rheumatological and gastroenterological tissues may favor timely attention and improve patients' quality of life.