Asunto(s)
Humanos , Esclerodermia Sistémica , Autoanticuerpos , Linfocitos B , Asociación , Tejido ConectivoRESUMEN
Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Etanercept/uso terapéutico , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Antirreumáticos/uso terapéutico , Femenino , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Farmacogenómica , Variantes Farmacogenómicas , Adulto JovenRESUMEN
To assess the discriminative utility of nail features detected by B-mode (BM) and color Doppler (CD) ultrasound (US) between patients with psoriasis (PsO) and psoriatic arthritis (PsA) and healthy controls. Sixty patients with PsA, 21 patients with PsO, and 20 healthy controls were prospectively included. All patients underwent a dermatologic assessment and PsA patients also a rheumatologic assessment. All patients and controls underwent a US assessment of the finger nails that included a BM score for nail plate integrity and four different CD scores based on the amount and location of CD signals in the nail bed/matrix. In addition, we measured the thickness of the nail bed (TNB) and nail plate (TNP). The BM score and the CD score based on the amount of signals in the nail bed in contact with the ventral plate discriminated between the control group (median, range 0.0, 0-4 and 2.0, 0-9, respectively) and the PsO/PsA group (median, range: 7.0, 0-31 and 5.14, 0-13, respectively) (p < 0.05) with or without clinical nail involvement. The CD scores based on the percentage of the nail bed/matrix occupied by Doppler signals did not discriminate between controls and PsO/PsA patients. TNB and TNP were significantly higher in psoriatic nails with or without clinical involvement than in control nails. In PsO/PsA patients, the BM score, TNB and TNP were significantly higher in clinically involved nail than in clinically non-involved nails. Our results showed discriminative utility of BM US and some CD US features for PsO/PsA nails.
Asunto(s)
Artritis Psoriásica/diagnóstico por imagen , Uñas/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/diagnóstico por imagen , Ultrasonografía , Ultrasonografía Doppler en ColorRESUMEN
OBJECTIVES: To compare colour Doppler (CD) versus power Doppler (PD) semiquantitative and quantitative scoring of synovial vascularisation and to evaluate the relationship between semiquantitative and quantitative scores in patients with rheumatoid arthritis (RA). METHODS: One hundred RA patients underwent B-mode, PD, and CD assessments of 12 joints at two European centres. Each joint with synovial hypertrophy (SH) detected on B-mode was semiquantitatively scored (0-3) for PD (SPD score) and CD (SCD score) synovial signal. PD and CD synovial signal were also quantitatively scored (0-100%) (QPD and QCD scores, respectively) using a software integrated in the US equipment for counting the colour fraction. RESULTS: We found SH in 184 joints. SPD and SCD agreed in 92.3% (95%CI: 88.4; 96.2%) of paired scores, with Kendall rank correlation coefficient tau-b=0.95. QPD and QCD scores were highly correlated (Pearson's coefficient=0.70) but Blamd-Altman plot showed insufficient agreement, being the QCD scores systematically slightly higher than the QPD scores. The comparison of mean values of QPD and QCD between scores of SPD and SCD, respectively, showed significant differences between grade 0 and grade 1 (p<0.001), and grade 2 and grade 3 (p=0.042 and p=0.007, respectively) but not between grade 1 and 2 (p=0.154 and p=0.150, respectively). CONCLUSIONS: The SPD and SCD scores were concordant and the QPD and QCD scores highly correlated but were not concordant. There was an overlap between SPD and SCD mild and moderate scores regarding QPD and QCD scores.
Asunto(s)
Artritis Reumatoide/diagnóstico por imagen , Neovascularización Patológica , Membrana Sinovial/irrigación sanguínea , Membrana Sinovial/diagnóstico por imagen , Ultrasonografía Doppler en Color , Ultrasonografía Doppler/métodos , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/patología , Estudios Transversales , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Italia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , España , Adulto JovenRESUMEN
To identify features associated with long-term persistent remission in rheumatoid arthritis (RA) patients on tapered biological disease-modifying antirheumatic drugs (bDMARD) (tap-bDMARD) therapy. We carried out a 40-month (m) extension follow-up study of 77 RA patients from a previous 12 m tap-bDMARD study. Disease activity was assessed at baseline and every 3 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy (SH) and synovial power Doppler signal (i.e., Doppler synovitis) was performed before starting the tap-bDMARD strategy by a rheumatologist blinded to clinical and laboratory data. At the 40 m mark, 44 (57.1%) patients failed the tap-bDMARD strategy, while 33 (42.9%) succeeded. Patients who presented a failed tap-bDMARD had significantly longer disease duration, a longer time from symptom onset to synthetic (s) DMARD start, longer duration of sDMARD treatment, a greater number of sDMARDs, and a higher baseline DAS28 and SDAI than patients with successful tap-bDMARD at 40 months. In logistic regression analysis, the presence of baseline Doppler synovitis, a DAS28 ≥ 2.2, and the presence of rheumatoid factor were identified as predictors of tap-bDMARD failure at 40 m. In those patients who succeed tap-bDMARD at 12 m, a smoking habit was significantly more frequently found in tap-bDMARD failures at 40 m. Our results showed that DAS28 and the presence of Doppler synovitis, RF and a smoking habit predicted long-term tap-bDMARD failure.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Sinovitis/diagnóstico por imagen , Anciano , Antirreumáticos/farmacología , Artritis Reumatoide/diagnóstico por imagen , Productos Biológicos/farmacología , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Inducción de Remisión , Factor Reumatoide/sangre , Factor Reumatoide/efectos de los fármacos , Factores de Tiempo , Insuficiencia del Tratamiento , Ultrasonografía Doppler/métodosRESUMEN
La interleucina (IL) 6 es una citocina pleiotrópica que regula múltiples procesos biológicos y tiene un papel cardinal en la fisiopatología de la artritis reumatoide. La IL-6 participa no solo en el proceso inflamatorio y las respuestas inmune innata y adaptativa, sino también en la hematopoyesis, la estimulación del eje hipotálamohipofisario-adrenal, la regulación de las respuestas de fase aguda y el metabolismo óseo y lipídico. A diferencia de otras citocinas, la IL-6 puede activar la señalización celular a través de receptores de membrana y receptores solubles. A nivel local, valores elevados de IL-6 en el líquido sinovial en pacientes con artritis reumatoide favorecen el desarrollo del pannus y la resorción ósea como resultado de la osteoclastogénesis, lo que aumenta el riesgo de destrucción articular. En esta revisión se describe el papel que desempeña la IL-6 a nivel articular y a nivel sistémico, para destacar la importancia que tiene como diana terapéutica en la artritis reumatoide
Interleukin (IL)-6 is a pleiotropic cytokine that regulates multiple biological processes and plays a cardinal role in the pathogenesis of rheumatoid arthritis (RA). IL-6 participates not only in the inflammatory process and innate and adaptive immune responses, but also in hematopoiesis, stimulation of the hypothalamic-pituitary-adrenal axis, acute-phase responses and bone and lipid metabolism. Unlike other cytokines, IL-6 can activate cell signalling through membrane receptors and soluble receptors. At a local level, high IL-6 levels in the synovial fluid of patients with RA promote the development of pannus and bone resorption as a result of osteoclastogenesis, thus increasing the risk of bone destruction. This review discusses the central role of IL-6 in RA at both the articular and systemic levels to highlight its role as an important therapeutic target in this disease
Asunto(s)
Humanos , Artritis Reumatoide/fisiopatología , Interleucina-6/fisiología , Citocinas/fisiología , Artropatías/fisiopatología , Anemia/fisiopatología , Osteoporosis/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Dislipidemias/epidemiología , Fatiga/epidemiologíaRESUMEN
Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Marcadores Genéticos/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
No disponible
Asunto(s)
Humanos , Inhibidor de Coagulación del Lupus/análisis , Síndrome Antifosfolípido/diagnóstico , Anticuerpos Antifosfolípidos/análisis , Factores de Riesgo , Biomarcadores/análisisRESUMEN
La enfermedad mixta del tejido conectivo (EMTC) es una enfermedad reumática autoinmunitaria sistémica (ERAS) caracterizada por la asociación de manifestaciones clínicas de lupus eritematoso sistémico (LES), esclerosis sistémica cutánea (ESC) y polimiositis-dermatomiositis en presencia de títulos elevados de anticuerpos anti-U1-RNP en el suero de los pacientes. Sus principales síntomas son la poliartritis, el edema de manos, el fenómeno de Raynaud, la esclerodactilia, la miositis y la hipomotilidad esofágica. Actualmente, la mayoría de los autores acepta que la EMTC es una entidad independiente, pero algunos mantienen que estos pacientes podrían presentar una ERAS, definida en su fase precoz como LES o ESC, o ser, en realidad, un síndrome de solapamiento de la ERAS (AU)
Mixed connective tissue disease (MCTD) is a systemic autoimmune rheumatic disease (SARD) characterised by the combination of clinical manifestations of systemic lupus erythematosus (SLE), cutaneous systemic sclerosis (SSc) and polymyositis-dermatomyositis, in the presence of elevated titers of anti-U1-RNP antibodies. Main symptoms of the disease are polyarthritis, hand oedema, Raynaud's phenomenon, sclerodactyly, myositis and oesophageal hypomobility. Although widely discussed, most authors today accept MCTD as an independent entity. Others, however, suggest that these patients may belong to subgroups or early stages of certain definite connective diseases, such as SLE or SSc, or are, in fact, SARD overlap syndromes (AU)
Asunto(s)
Humanos , Enfermedad Mixta del Tejido Conjuntivo/epidemiología , Enfermedad Mixta del Tejido Conjuntivo/prevención & control , Ribonucleoproteína Nuclear Pequeña U1/análisis , Enfermedad Mixta del Tejido Conjuntivo/diagnóstico , Enfermedad Mixta del Tejido Conjuntivo/fisiopatología , Artritis/complicaciones , Edema/complicaciones , Enfermedad de Raynaud/complicaciones , Miositis/complicacionesRESUMEN
Mixed connective tissue disease (MCTD) is a systemic autoimmune rheumatic disease (SARD) characterised by the combination of clinical manifestations of systemic lupus erythematosus (SLE), cutaneous systemic sclerosis (SSc) and polymyositis-dermatomyositis, in the presence of elevated titers of anti-U1-RNP antibodies. Main symptoms of the disease are polyarthritis, hand oedema, Raynaud's phenomenon, sclerodactyly, myositis and oesophageal hypomobility. Although widely discussed, most authors today accept MCTD as an independent entity. Others, however, suggest that these patients may belong to subgroups or early stages of certain definite connective diseases, such as SLE or SSc, or are, in fact, SARD overlap syndromes.
Asunto(s)
Enfermedad Mixta del Tejido Conjuntivo/diagnóstico , Diagnóstico Diferencial , Disentimientos y Disputas , Humanos , Enfermedad Mixta del Tejido Conjuntivo/mortalidad , Enfermedad Mixta del Tejido Conjuntivo/terapiaRESUMEN
OBJECTIVES: The aim of this study was to investigate the relationship between serum infliximab (IFX) levels and changes of RF and ACPA levels in patients with rheumatoid arthritis (RA). METHODS: Enzyme-linked immunosorbent assays (ELISA) [Promonitor® IFX R1 (version 2) (Progenika Biopharma, Spain)] were used to measure drug levels and antidrug-antibodies (ADAb) in IFX RA-treated patients (n=19). Disease activity was assessed using DAS28. IgM rheumatoid factor (RF) and IgM, IgA and IgG anti-cyclic citrullinated peptide (ACPA) were determined through ELISA. RESULTS: A significant decrease in RF (p=0.01), ACPA IgG (p=0.007), IgM (p=0.01) and IgA (p=0.03) was observed in patients presenting adequate levels of serum IFX. No significant changes to RF or ACPA were observed in patients with undetectable IFX. CONCLUSIONS: Data from this study support the hypothesis that the anti-TNF antagonist IFX downregulates autoantibody levels in RA patients when IFX levels are detectable. Larger-scale studies need to be performed to establish RF and ACPA presence as therapeutic response predictive factors.
Asunto(s)
Anticuerpos Antiproteína Citrulinada/sangre , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Infliximab/uso terapéutico , Péptidos Cíclicos/inmunología , Factor Reumatoide/sangre , Adulto , Anciano , Antirreumáticos/sangre , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Biomarcadores/sangre , Regulación hacia Abajo , Monitoreo de Drogas/métodos , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Infliximab/sangre , Masculino , Persona de Mediana Edad , Proyectos Piloto , Factores de Tiempo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , Adulto JovenAsunto(s)
Síndrome Antifosfolípido/diagnóstico , Inhibidor de Coagulación del Lupus/sangre , Lupus Eritematoso Sistémico/diagnóstico , Complicaciones del Embarazo/prevención & control , Trombosis/prevención & control , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/complicaciones , Enfermedades Asintomáticas , Biomarcadores/sangre , Femenino , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/etiología , Medición de Riesgo , Factores de Riesgo , Trombosis/sangre , Trombosis/etiologíaRESUMEN
No disponible
Asunto(s)
Humanos , Masculino , Femenino , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/inmunología , Vacunación/métodos , Vacunación/normas , Vacunación/tendencias , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Resultado del TratamientoAsunto(s)
Enfermedades Autoinmunes/inmunología , Huésped Inmunocomprometido , Inflamación/inmunología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Enfermedades Autoinmunes/complicaciones , Humanos , Inflamación/complicaciones , Guías de Práctica Clínica como AsuntoRESUMEN
Several genome-wide association studies have identified a polymorphism located 35 kb upstream of the coding region of HLA-C gene (rs9264942; termed -35 C/T) as a host factor significantly associated with the control of HIV-1 viremia in untreated patients. The potential association of this host genetic polymorphism with the viral reservoirs has never been investigated, nor the association with the viral control in response to the treatment. In this study, we assess the influence of the polymorphism -35 C/T on the outcome of virus burden in 183 antiretroviral-naïve HIV-1-infected individuals who initiated antiviral treatment (study STIR-2102), analyzing HIV-1 RNA viremia and HIV-1 DNA reservoirs. The rs9264942 genotyping was investigated retrospectively, and plasma levels of HIV-1 RNA and peripheral blood mononuclear cell- (PBMC-) associated HIV-1 DNA were compared between carriers and noncarriers of the protective allele -35 C before antiretroviral therapy (ART), one month after ART and at the end of the study (36 months). HIV-1 RNA and HIV-1 DNA levels were both variables significantly different between carriers and noncarriers of the allele -35 C before ART. HIV-1 DNA levels remained also significantly different one month posttherapy. However, this protective effect of the -35 C allele was not maintained after long-term ART.
Asunto(s)
Reservorios de Enfermedades/virología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , VIH-1/fisiología , Antígenos HLA-C/genética , Adulto , Antivirales/uso terapéutico , Enfermedades Asintomáticas , Enfermedad Crónica , ADN Viral/sangre , Femenino , Estudios de Seguimiento , Genotipo , Interacciones Huésped-Patógeno/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple , ARN Viral/sangre , ViremiaRESUMEN
No disponible
Asunto(s)
Humanos , Animales , Inhibidores de Fosfodiesterasa/inmunología , Inhibidores de Fosfodiesterasa/uso terapéutico , Autoinmunidad/inmunología , Autoinmunidad/fisiología , Inflamación/complicaciones , Inflamación/diagnóstico , Inflamación/inmunología , Resultado del Tratamiento , Evaluación de Eficacia-Efectividad de Intervenciones , Citocinas/uso terapéutico , Receptores de Citocinas/biosíntesisRESUMEN
No disponible
Asunto(s)
Humanos , Femenino , Embarazo , Anticuerpos Monoclonales/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológico , Nutrientes/métodos , Artritis Reumatoide/complicaciones , Receptores de Citocinas , Inmunoglobulina G/análisis , Receptores de IgG/análisisRESUMEN
No disponible