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BACKGROUND: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory diseases in which innate and adaptive responses of the immune system are induced. RA and PsA have complex signaling pathways. Despite the differences in their clinical presentation, there is a great demand for fast and accurate diagnosis of diseases to implement treatment and plan an individual therapeutic strategy quickly. In this report, we present the results of differential diagnosis of patients with RA and PsA and healthy subjects (C, control group), allowing for reliable differentiation of groups of rheumatoid patients based on biochemical parameters, attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectra, and combined data sets. MATERIALS AND METHODS: Biochemical analyses, ELISA (enzyme-linked immunosorbent assays), and multiplex assays were conducted for blood sera from patients with RA (n = 32), patients with PsA (n = 28), and the control group (n = 18). ATR-FTIR spectra were collected for lyophilized sera. RESULTS: The combination of six biochemical parameters (WBC, ESR, RF, CRP, HCC-4/CCL16, and HMGB1/HMGB) allowed the development of the partial least squares discriminant analysis (PLS-DA) model with an overall accuracy (OA) of 80% for test samples. The best separation between RA, PsA, and the control group was obtained utilizing spectral data. Using the interval PLS algorithm (iPLS) specific spectral ranges were selected and a classifier characterized by OA value for test set equal to 88% was obtained. This parameter, for the hybrid PLS-DA model constructed using selected biochemical parameters and a significantly reduced number of spectral variables, reached the level of 84%. CONCLUSIONS: PLS-DA models developed on the basis of spectral data enable effective differentiation of patients with RA, patients with PsA, and healthy subjects. They appeared to be insensitive to existing inflammation processes which opens interesting perspectives for new diagnostic tests and algorithms for identification of patients with RA and PsA.
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Artritis Psoriásica , Artritis Reumatoide , Biomarcadores , Humanos , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/sangre , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Diagnóstico Diferencial , Persona de Mediana Edad , Biomarcadores/sangre , Proyectos Piloto , Masculino , Femenino , Adulto , Análisis de los Mínimos Cuadrados , Análisis Discriminante , Anciano , Estudios de Casos y ControlesRESUMEN
The broad spectrum of interactions between autoimmune diseases and the SARS-CoV-2 vaccination is not fully understood. This study aims to evaluate the prevalence of anti-nuclear antibodies (ANA), anti-ENA, anticardiolipin antibodies (ACL), and anti-beta-2 glycoprotein I antibodies (anti-ß2GPI) before and after the SARS-CoV-2 mRNA vaccination in a real-life setting in healthcare professionals. The identification of risk factors associated with vaccine immunogenicity was evaluated. The study group consisted of employees of two hospitals (354 individuals). Samples for antibody assays were collected before vaccination and at 7-9 months after complete immunisation. There was no significant increase in the prevalence of ANA, ACL or anti-ß2GPI antibodies, or autoimmune diseases in subjects who were vaccinated 7-9 months after complete immunisation. In terms of detected anti-ENA, the anti-DFS70 antibodies were found in 6 times more subjects than before vaccination at the second blood draw (in 18 and 3 subjects, respectively) (p = 0.001). There were no significant relationships between a SARS-CoV-2 infection history, humoral response, cellular response, subject category, smoking, sex, body weight, ANA, anti-ENA, ACL, or anti-ß2GPI. This study revealed a possible association between the severity of vaccine adverse events (VAEs) and ANA titre. Individuals with more severe VAEs (>10 points) after the second dose of the vaccine had significantly higher ANA titre after complete immunization. When analysing the significance of time between the ANA, anti-ENA, ACL, and anti- ß2GPI assays and complete immunisation antibody values, no qualitative result was statistically significant. There was correlation between the time since complete immunization and ANA after.
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Enfermedades Autoinmunes , Vacunas contra la COVID-19 , COVID-19 , Humanos , Anticuerpos Antivirales , Autoanticuerpos , Enfermedades Autoinmunes/etiología , Autoinmunidad , beta 2 Glicoproteína I , COVID-19/prevención & control , COVID-19/etiología , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2/genética , Vacunación/efectos adversosRESUMEN
Vaccination is the best way to limit the extent of the COVID pandemic. Knowledge of the duration of the immune response will allow the planning of a vaccination protocol. This study aims to validate the complete (humoral and cellular) immune responses over time in large population groups following the full vaccination of healthcare professionals in real-life conditions and to assess the relationship between antibody levels and T-cell activity in relation to the characteristics of the study group. The samples for the study were obtained from volunteers (staff of two hospitals) on three occasions: before vaccination, T0, then 4-9 weeks after full vaccination (two doses BNT162b2), T1, and 7-9 months after vaccination, T2. The humoral response was investigated by the titre of anti-SARS-CoV-2 IgG antibodies to S1 protein. Assays were performed three times at intervals. The cellular response was assessed in a subgroup of 189 subjects by QuanT-Cell SARS-CoV-2 (IGRA). The assay was performed once. A group of 344 subjects fully vaccinated with the BNT162b2 vaccine were included in the study. The humoral response was observed in 100% of subjects at both 4-7 weeks and 7-9 months, but antibody titres fell by almost 90% in this interval. The cellular response was observed in 94% (177/189) of subjects 7-9 months after the second dose of vaccine. In subjects with a negative cellular response, eight out of 12 smoked. A factor associated with greater immunogenicity of vaccination was past SARS-CoV-2 infection. The administration of full BNT162b2 vaccination (two doses) induces humoral and cellular responses detectable even more than six months after vaccination. Smoking may be a factor associated with impaired cellular response to vaccination.
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BACKGROUND: Medical workers are a group that is particularly vulnerable to infection during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVES: The study aimed to assess the risk of COVID-19 infection and its course in the medical staff of a COVID-only and a non-COVID hospital. MATERIAL AND METHODS: The observational study included 732 participants who were medical workers. The study was conducted between June 2020 and December 2020, before widespread COVID-19 immunization was introduced. RESULTS: Of the 732 employees of the hospitals, 377 had a history of COVID-19. The risk of disease was twice as high in the medical staff of the COVID-only hospital compared to the medical staff of the non-COVID hospital (odds ratio (OR) = 2.0; p < 0.001). Among medical personnel, 20.6% of the participants were asymptomatic and 6.4% required hospitalization. For the non-COVID hospital, the employees who were most frequently infected with COVID-19 were nurses/paramedics/medical caretakers. The factor influencing the risk of infection was body mass index (BMI; OR = 1.05; p = 0.004). The risk of COVID-19 infection was lower in the influenza vaccine group (OR = 2.23, p < 0.001). CONCLUSIONS: The study results indicate that employees of the hospital treating only COVID patients have a higher risk of infection. Previous observations on factors predisposing to COVID-19 infection like gender and BMI were confirmed. However, the observations carried out on the studied population did not confirm the influence of other factors, such as the coexistence of chronic diseases (apart from diabetes) on the risk of developing COVID-19. In addition, we noticed that seasonal influenza vaccination has a beneficial effect in patients with COVID-19 infection.
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COVID-19 , Vacunas contra la Influenza , COVID-19/epidemiología , Hospitales , Humanos , Cuerpo Médico , SARS-CoV-2RESUMEN
Methotrexate (MTX) is recommended as a first-line treatment for rheumatoid arthritis (RA). There are no strict guidelines regarding monitoring for liver damage in RA patients. This study aimed to evaluate noninvasive diagnostic procedures in assessing liver fibrosis in RA patients. Ninety-six RA patients were recruited for this study. The procollagen III N-terminal peptide (PIIINP) serum level was measured in all patients. The Enhanced Liver Fibrosis score (ELF-1) was calculated for 82 patients. Transient elastography (TE) was performed in 91 patients, those examined were divided into two groups: a study and control group, comprising patients with and without risk factors for liver fibrosis, respectively. The TE result correlated only with the body mass index-BMI (p < 0.05); there was no correlation with the cumulative MTX dose (p = 0.33). The TE result was significantly higher in those with risk factors for liver fibrosis than in those without risk factors (TE result > = 7.1 kPa 28/42 vs 13/41, HR = 2.103, Mann-Whitney U test, approximately 0.02). There was a positive correlation between the PIIINP level and body weight (p = 0.028), cumulative MTX dose (p = 0.007), RA activity (p = 0.028) and diabetes mellitus (DM) (p = 0.001). There was a positive correlation between the ELF-1 score and age (p < 0.001), cumulative MTX dose (p = 0.007) and RA activity (p < 0.001). The PIIINP level and ELF-1 score are not organ specific, and readings may vary depending on RA activity. TE is organ specific and can be performed by a skilled ultrasonographer might be useful to assess actual liver condition.
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Artritis Reumatoide , Enfermedad Hepática Inducida por Sustancias y Drogas , Diagnóstico por Imagen de Elasticidad , Hepatopatías , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico por imagen , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Humanos , Cirrosis Hepática/inducido químicamente , Metotrexato/efectos adversosRESUMEN
INTRODUCTION: The purpose of the study was to investigate whether single-nucleotide polymorphisms (SNPs) IL-6 -174 G/C and IL-6R Asp358Ala are associated with susceptibility to psoriatic arthritis (PsA) or affect response to treatment with methotrexate (MTX). PATIENTS AND METHODS: Seventy-four patients diagnosed with PsA and qualified for MTX treatment were enrolled to the study. The control group consisted of 120 healthy individuals. Polymorphisms IL-6 -174 G/C and IL-6R Asp358Ala were genotyped using a polymerase chain reaction (PCR) amplification employing LightSNiP assays. RESULTS: A significant association between the IL-6 -174 CC genotype and an improved clinical outcome of MTX therapy was observed. A good response was more frequently observed among PsA patients bearing the IL-6 -174 CC genotype than patients with the GC or GG genotypes (P = 0.007). On the other hand, patients carrying the IL-6 -174 GC genotype less frequently responded to MTX treatment as compared to patients with other genotypes (P = 0.006). With respect to the IL-6R Asp358Ala SNP, there were no significant differences in genotype and allelic frequencies in relation to clinical outcome of MTX treatment. No association was found between the IL-6 -174 G/C or IL-6R Asp358Ala SNPs and PsA susceptibility. CONCLUSION: Results from this study provide evidence that the IL-6 -174 G/C polymorphism might influence efficacy of MTX treatment.
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MHC class I polypeptide-related sequence A (MICA) is a stress-induced protein involved in activation of NK and T cells through interaction with NKG2D receptor. These molecules are atypically expressed in synovium of patients diagnosed with rheumatoid arthritis (RA). A total of 279 patients with RA, qualified to TNF-blockade therapy, were genotyped for MICA rs1051792 SNP. The effectiveness of anti-TNF agents was assessed with European League Against Rheumatism criteria. Significant relationship between MICA rs1051792 and outcome of TNF-blockade therapy has been found. The MICA rs1051792 GG genotype was overrepresented in patients non-responsive to anti-TNF drugs in comparison with other genotypes (p = 0.010). On the other hand, beneficial therapeutic response was more frequently detected among RA subjects possessing heterozygous genotype than those with homozygous genotypes (p = 0.003). Furthermore, increased MICA concentrations in serum were observed in patients possessing MICA rs1051792 GG genotype as compared with those with GA or AA genotypes (p = 1.8 × 10-5). The results from this study indicate the potential influence of MICA rs1051792 polymorphism on modulation of therapeutic response to TNF-blockade treatment in RA.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/sangre , Artritis Reumatoide/genética , Antígenos de Histocompatibilidad Clase I/sangre , Antígenos de Histocompatibilidad Clase I/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Anciano , Antirreumáticos/farmacología , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Metionina/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Resultado del Tratamiento , Valina/genéticaRESUMEN
The aim of this study was to assess the prevalence of periodontal disease and the effect of periodontal treatment in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Forty-four RA patients, thirty SpA patients and thirty-nine healthy volunteers were recruited to the study. Periodontal examination included the approximal plaque index (API), bleeding on probing (BoP), probing depth (PD) and number of teeth. Samples from the deepest periodontal pockets were taken for the detection of Porphyromonas gingivalis DNA with the use of the polymerase chain reaction. All subjects with periodontitis, who completed the study, received periodontal treatment consisting of scaling/root planing and oral hygiene instructions. Disease activity scores, clinical and laboratory parameters were assessed before and 4-6 weeks after periodontal treatment. No significant difference in the prevalence of periodontal disease and the presence of P. gingivalis DNA were found in RA and SpA patients compared to healthy controls. Significantly higher API (80% vs 63%; p = 0.01) and a lower number of teeth (20 vs 25, p = 0.001) were found in RA patients. BoP was significantly elevated in SpA patients (51% vs 33%, p = 0.02). Disease activity measured by the DAS28(CRP) was significantly reduced in RA patients after periodontal treatment (p = 0.002). Clinical and biochemical parameters were not improved in SpA patients. Nonsurgical periodontal treatment had an impact on the decrease in RA activity. Periodontal examination is necessary in patients with RA to detect and treat periodontitis at an early stage.
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Artritis Reumatoide/epidemiología , Enfermedades Periodontales/epidemiología , Aplanamiento de la Raíz , Espondiloartritis/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Periodontales/terapia , Porphyromonas gingivalis/aislamiento & purificación , Prevalencia , Índice de Severidad de la Enfermedad , Espondiloartritis/diagnóstico , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of the study was to evaluate the frequency of anti-mutated citrullinated vimentin antibodies (a-Sa), anti-citrullinated α-enolase peptide 1 antibodies (a-CEP-1), anti-filaggrin antibodies (AFAs), heterogeneous nuclear ribonucleoprotein compies/anti-RA33-antibodies (a-hnRNP/RA33), anti-carbamylated protein antibodies (a-CarP), and metalloproteinase (MMPs) activity in patients with early inflammatory arthritis (EIA). METHODS: Seventy-four patients with EIA: 51 diagnosed with RA (rheumatoid arthritis) and 23 with UA (undifferentiated arthritis), and 20 healthy volunteers were enrolled to the study. Inflammatory markers, rheumatoid factor (RF), and antibodies mentioned above were assessed in all patients. RESULTS: In the EIA group, we observed significantly higher concentration of a-CEP-1 (65.8 ± 111.6 RU/mL) than in controls (2.0 ± 0.0 RU/mL). In RF(+) RA patients, we observed higher concentration of a-Sa and a-CEP-1 than in other groups. A-Sa were positive in 69% of RF(+) RA, 37% of RF(-) RA, 26% of UA patients and in 10% of controls. A-CEP-1 were positive in 77% of RF(+) RA patients, in 56% of RF(-) RA patients, in 8.7% of UA patients, but they were negative in controls. In patients with RF(+) RA, positive a-CarP were present statistically significantly more often than in RF (-) RA patients. No statistically significant difference in frequency of a-hnRNP/RA33 and AFA between RF(+) RA, RF(-) RA, and UA was observed. CONCLUSIONS: Our results suggest that a-CEP-1 may help in differentiation between RF(-) RA and UA. a-CEP-1 and a-Sa may be useful while diagnosing EIA. a-CarP may be used in differentiation of RA RF(-) and UA. However, a follow-up study is needed to evaluate the prognostic value of analyzed antibodies.
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Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Metaloproteinasas de la Matriz Secretadas/metabolismo , Adulto , Anciano , Anticuerpos Antiproteína Citrulinada/inmunología , Artritis/inmunología , Artritis/metabolismo , Artritis Reumatoide/metabolismo , Biomarcadores de Tumor/inmunología , Estudios de Casos y Controles , Proteínas de Unión al ADN/inmunología , Femenino , Proteínas Filagrina , Ribonucleoproteínas Nucleares Heterogéneas/inmunología , Humanos , Proteínas de Filamentos Intermediarios/inmunología , Masculino , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Fosfopiruvato Hidratasa/inmunología , Carbamilación de Proteína , Factor Reumatoide/inmunología , Proteínas Supresoras de Tumor/inmunologíaRESUMEN
BACKGROUND: Cognitive impairment (CI) is a frequent problem in lupus patients, regardless of their overt neuropsychiatric (NP) involvement. OBJECTIVES: The aim of our study was to test cognitive abilities in systemic lupus erythematosus (SLE) patients by means of neuropsychological testing and event-related potentials (ERPs), and to search for their cognitive abilities correlations with a wide range of auto-antibodies. MATERIAL AND METHODS: A total of 37 SLE patients were subjected to a battery of neuropsychological tests, recommended by the American College of Rheumatology (ACR), and to ERPs. They were also tested for a wide range of auto-antibodies (anti-cardiolipin (aCL), anti-ß2-glycoprotein I (anti-ß2-GPI), lupus anticoagulant, anti-dsDNA, anti-nucleosome, anti-ribosomal P (anti-Rib-P), anti-ganglioside, anti-Ro/SS-A, and anti-La/SS-B. RESULTS: Cognitive impairment was found in 35% of patients, mostly with NP SLE (NPSLE), and was associated with higher disease activity, measured by the SLE Disease Activity Index (SLEDAI), and with a longer duration of central nervous system (CNS) involvement. There were no differences in the immunological status between CI patients and those without cognitive decline, but some antibodies were correlated with worse results in certain neuropsychological tests (anti-dsDNA and worse results of Rey Complex Figure Test - RCFTc for copying and RCFTr for recall, and of verbal fluency test (VFT); aCL IgG and worse results in Digit Span (DS) and in RCFTc). Event-related potentials showed prolonged N200 and P300 latencies in SLE patients in comparison to controls, but no differences were found between SLE and NPSLE patients. Mean P300 latency was significantly longer in patients without anti-nucleosome antibodies. CONCLUSIONS: Event-related potentials can be used as a complementary tool in assessing CI in SLE patients. The immunological status of patients with CI did not differ from that of patients without cognitive problems.
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Anticuerpos Antinucleares/inmunología , Trastornos del Conocimiento/inmunología , Trastornos del Conocimiento/fisiopatología , Potenciales Evocados , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/fisiopatología , Vasculitis por Lupus del Sistema Nervioso Central/inmunología , Vasculitis por Lupus del Sistema Nervioso Central/fisiopatología , Pruebas Neuropsicológicas , Trastornos del Conocimiento/sangre , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/psicología , Vasculitis por Lupus del Sistema Nervioso Central/sangre , Vasculitis por Lupus del Sistema Nervioso Central/psicología , beta 2 Glicoproteína IRESUMEN
Genes involved in regulation of the nuclear factor-κB (NF-κB)-pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of TLR2, TLR4, TLR9 and NF-κB1 genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-α therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for TLR2 (rs111200466), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and NF-κB1 (rs28362491) alleles. The presence of the TLR9 -1486 T variant (p < 0.0001) and its homozygosity (p < 0.0001) were found to be associated with disease susceptibility. The TLR9 -1237 C allele was associated with predisposition to RA in females only (p = 0.005). Moreover, the TLR4 rs4986791 G (rs4986790 T) alleles were more frequently detected among patients with the stage IV disease (p = 0.045), and were associated with more effective response to anti-TNF-α therapy (p = 0.012). More efficient response to anti-TNF-α treatment was also observed in patients with del within the NF-κB1 gene (p = 0.047), while for the TLR9 -1486 T homozygotes, the treatment was ineffective (p = 0.018). TLR polymorphisms affect disease susceptibility and response to therapy with TNF-α inhibitors in RA patients of Caucasian origin.
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Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , FN-kappa B/metabolismo , Polimorfismo de Nucleótido Simple , Transducción de Señal , Adolescente , Adulto , Anciano , Alelos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , FN-kappa B/genética , Factores de Riesgo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Research is still being conducted in order to determine the mechanisms responsible for the initiation of rheumatoid arthritis (RA) as well as for its persistence and progression. OBJECTIVES: The aim of this work was to establish the expression of the signal transducer and activator of transcription (STAT) transcription factors and the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) transcription factor in peripheral blood leukocytes and synovial fluid cells. The correlations between the activation level of the transcription factors and the activity of the disease were also analyzed. MATERIAL AND METHODS: In total, the study included 34 RA patients and 19 healthy individuals as controls. The expression of NFκB, STAT1, STAT3, STAT4, STAT5 and STAT6 in peripheral blood leukocytes and synovial fluid cells was established. The immunocytochemistry method was used to determine the degree of activation of STAT and NF-κB transcription factors. For the location of the factors, primary polyclonal anti-STATs and monoclonal anti-NF-κB antibodies were used. RESULTS: The expression of STAT1, STAT3, STAT4, STAT5, STAT6 and NFκB was significantly higher in the group of RA patients than in the controls. No statistically significant differences were found between the expression of STATs in peripheral blood leukocytes and synovial fluid cells. CONCLUSIONS: In comparison with the control group, the expression of the STAT and NFκB transcription factors in RA patients was higher, which may be helpful in better understanding the etiopathogenesis of the disease in the future, and may potentially have important therapeutic implications.
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Artritis Reumatoide/metabolismo , Quinasas Janus/metabolismo , FN-kappa B/metabolismo , Factores de Transcripción STAT/metabolismo , Adulto , Anciano , Femenino , Humanos , Quinasas Janus/análisis , Masculino , Persona de Mediana Edad , FN-kappa B/análisis , Factores de Transcripción STAT/análisis , Adulto JovenRESUMEN
BACKGROUND: The etiology of axial spondyloarthritis (axSpA) is not fully elucidated. Research continues in determining the mechanisms responsible for initiation of the disease process, its maintenance and development. OBJECTIVES: The aim of this study was to evaluate the expression of transcription factors STAT (signal transducer and activator of transcription) and NF-κB (nuclear factor kappa B) as well as Janus kinase3 (JAK3) in the peripheral blood leukocytes. We also analyzed the connection between the degree of activation of transcription factors and the disease activity. MATERIAL/METHODS: The study involved 46 patients with axSpA and 19 healthy individuals who comprised the control group. The expression of NF-κB, STAT1, STAT3, STAT4, STAT5, STAT6, and JAK3 in peripheral blood leukocytes was assessed. To determine the degree of activation of transcription factors STAT-s and NF-κB and JAK3 kinase, the immunocytochemistry method was used. For location of the factors, the primary monoclonal anti-NF-κB, anti-JAK3 and polyclonal anti-STAT-s antibodies were used (Chemicon International, USA, Abcam, Cambridge, UK), and the set of antibodies Novocastain Super ABC Kit (Novocastra, UK). RESULTS: Expression of STAT1, STAT3, STAT4, STAT5, STAT6, NF-κB and JAK3 was statistically higher in the group of patients with axSpA than in the control group. There was a positive correlation with ESR values and expression of STAT4. There was no correlation between STAT, NF-κB, and JAK3 expression and ASDAS, BASDAI, and BASFI. Nine patients were treated with TNF-α inhibitors. The expression of NF-κB and STAT6 was higher in the group treated with TNF-α inhibitors, even though disease activity in these patients was shown to be lower than in those not receiving such treatment (ASDAS = 1.34±0.51 vs. 3.52±0.90, BASDAI = 2.34±1.92 vs. 5.51±2.41). CONCLUSIONS: In the group of patients with axSpA compared with the control group, higher expression of the transcription factors STAT and NF-κB as well as JAK3 was observed. Due to its crucial roles in inflammation and autoimmunity, STAT4 may have promise as an effective therapeutic target for axSpA.
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Janus Quinasa 3/genética , Leucocitos/metabolismo , FN-kappa B/genética , Factores de Transcripción STAT/genética , Espondiloartritis/metabolismo , Adulto , Anciano , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVES: Current studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA). In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33) correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis. MATERIAL AND METHODS: Forty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA) and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patient's medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS), the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined. RESULTS: In patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 ±184.0 pg/ml vs. 14.0 ±17.1 pg/ml, p < 0.0001 and 45.5 ±71.9 pg/ml vs. 18.4 ±14.3 pg/ml, p < 0.0001, respectively). Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 ±246.9 pg/ml vs. 99.9 ±105.9 pg/ml, p = 0.0001) was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 ±8.50 pg/ml vs. 2.04 ±2.98 pg/ml, p = 0.0295). No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity. CONCLUSIONS: We report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may predispose to a more severe course of aSpA.
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Among the complex network of inflammatory cells involved in the pathogenesis of rheumatoid arthritis (RA), Th17 cells have recently been identified as key cells in the promotion of autoimmune processes, and joint destruction. The IL-23/Th17 signalling pathway, consisting of IL-23/IL-23R, IL-17A and IL-17F encoding genes, represents a candidate way for RA development with possible involvement in disease susceptibility and effect on disease progression. The present study aimed to determine the association between the polymorphic variants of the IL-17A (rs2275913), IL-17F (rs763780) and IL-23R (rs11209026) genes and RA susceptibility, progression and response to therapy with TNF-α inhibitors. Eighty-nine patients and 125 healthy individuals were investigated. The IL-17A polymorphism was found to affect RA progression and response to anti-TNF treatment. Female patients carrying the IL-17A wild-type genotype more frequently presented with stage 4 (8/24 vs. 6/47; p = 0.058) and were characterized by more active disease (the highest DAS28 score >5.1) after 3 months of therapy with the TNF inhibitors (12/23 vs. 15/45; p = 0.040). The IL-17F polymorphism appeared to be associated with susceptibility to the disease. The presence of the IL-17F minor variant (OR 3.97; p < 0.001) and its homozygosity (OR 29.62; p < 0.001) was more frequent among patients than healthy individuals. These results suggest that the polymorphisms within the IL-17A and IL-17F genes play a significant role in RA.
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Antirreumáticos/administración & dosificación , Artritis Reumatoide/diagnóstico , Interleucina-17/metabolismo , Receptores de Interleucina/metabolismo , Factores Sexuales , Células Th17/fisiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Adulto , Anciano , Animales , Antirreumáticos/farmacología , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Progresión de la Enfermedad , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Interleucina-17/genética , Masculino , Persona de Mediana Edad , Polonia , Polimorfismo de Nucleótido Simple , Pronóstico , Receptores de Interleucina/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Despite the fact that therapy with TNF-α inhibitors constitutes a breakthrough in rheumatoid arthritis management, no improvement is still achieved in approximately 30% of cases. The aim of the study was to evaluate whether single nucleotide polymorphisms (SNPs) within the TNF-α and TNF receptor encoding genes affect the efficacy of therapy with TNF-α inhibitors in patients with RA. METHODS: Five SNPs within the TNF-α and TNF receptor encoding genes (TNFA: G-308A, G-238A, C-857T; TNFR1A G36A; TNFR1B T676G) were determined in 280 RA patients who had been treated with TNF-α inhibitors for at least 6 months or they stop therapy because of adverse events. The association between the relative change in DAS28 and SNP genotypes was tested by linear regression. RESULTS: At week 24, low disease activity or remission was achieved by 45% of the patients. After 6 months remission of the disease or low disease activity were more frequently observed among patients homozygous for the TNFR1A 36A allele than among those who were GG homozygotes (52% vs. 34%, P=0.04). At week 24 DAS28 was significantly lower in the subgroup of patients homozygous for the TNFA-857T variant compared to the C allele carriers (P=0.045). The other polymorphisms were not found to be significantly associated with EULAR response at week 12 and 24 of the anti-TNF treatment. CONCLUSIONS: Homozygosity for the TNFR1A 36A allele and the TNFA-875T variant could act as a genetic factor associated with better response to anti-TNF treatment.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Receptores del Factor de Necrosis Tumoral/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
Psoriatic arthritis (PsA) is a complex genetic disorder that results from an interplay between multiple genetic and environmental factors. The aim of the study was to assess the significance of the association between the HLA-C and HLA-E allelic groups and PsA. Our results confirm the association between HLA-C(∗)06 and PsA (OR=5.16, p<0.0001). Furthermore, HLA-C(∗)06-positive patients develop more severe disease (p<0.01) and more frequently present with polyarticular pattern of PsA (p=0.08). Additionally our study revealed that the HLA-C(∗)02 allele was more frequently observed in PsA patients (OR=5.40, p<0.0005) and also that the HLA-E(∗)01:01 allele was significantly over-represented among HLA-C(∗)02-negative patients in comparison to healthy individuals (OR=6.44, p=0.045). Therefore these results suggest that the HLA-E and HLA-C(∗)02 molecules may also play an important role in determination immune response contributing to the PsA development.
Asunto(s)
Artritis Psoriásica/genética , Antígenos HLA-C/genética , Antígenos de Histocompatibilidad Clase I/genética , Artritis Psoriásica/inmunología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Antígenos HLA-C/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Masculino , Persona de Mediana Edad , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/inmunología , Antígenos HLA-ERESUMEN
OBJECTIVES: The aim of the study was to assess the concentration of anti-oxidized low-density lipoprotein (anti-oxLDL) antibodies and antibodies against oxLDL-beta2GPI (oxLDL-beta 2 glycoprotein I) complexes in the serum of patients with systemic lupus erythematosus (SLE). Correlations between clinical and laboratory factors and the intima media thickness (IMT) were also investigated. MATERIAL AND METHODS: The study included 16 patients (14 females, 2 males) with an established diagnosis of SLE. The mean disease duration was 6.3 years (range: 2-23 years). Thirteen age-matched healthy volunteers comprised the control group. IMT, the concentration of anti-oxLDL and anti-oxLDL-beta2GPI antibodies and lipid profile were assesed. Data concerning other cardiovascular risk factors were also collected. RESULTS: In the SLE group the intima media was significantly thicker than in control group. In the SLE group a statistically significant positive correlation was noted between age and mean IMT. Immunological assays revealed elevated serum concentration of anti-oxLDL antibodies in the SLE group; serum concentration of IgG anti-oxLDL-beta2GPI antibodies and IgM anti-oxLDL-beta2GPI antibodies were also elevated in the SLE group compared to the controls. There was a statistically significant positive correlation between LDL concentration and anti-oxLDL antibody concentration in the SLE group. CONCLUSIONS: The study findings support the thesis that cardiovasular risk is significantly higher in SLE patients. Elevated concentrations of anti-oxLDL antibodies, IgG anti-oxLDL-beta2GPI antibodies and IgM anti-oxLDL-beta2GPI antibodies were detected in the SLE group, which may contribute to the elevated cardiovascular risk in SLE patients.