RESUMEN
Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are influenced by genetic variants in immune system HLA genes. The Class II Major Histocompatibility Complex Transactivator (CIITA) is an important co-activator of the HLA transcriptional complex; the single nucleotide variant (SNV) rs3087456 localized in the gene promoter region (-168 A/G) has been reported as able to modify its transcription level. In our study, we assessed CIITA rs3087456 SNV in 1,044 Brazilians from two Brazilian regions (Northeast and South) to verify the association with susceptibility and clinical manifestations of (SLE) and (RA) using TaqMan SNP Genotyping Assays System. We observed a protection for a recessive model (GG x AA+AG) for RA susceptibility and increased risk for erosion development in AG genotype patients. No significant association was observed for SLE susceptibility; however, we observed significant increased risk for Class IV and V nephritis development in G allele and GG genotype patients. In conclusion, we showed the contribution of CIITA rs3087456 to SLE or RA clinical features and RA susceptibility in the studied populations.
Asunto(s)
Artritis Reumatoide , Lupus Eritematoso Sistémico , Proteínas Nucleares/genética , Transactivadores/genética , Artritis Reumatoide/genética , Estudios de Casos y Controles , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lupus Eritematoso Sistémico/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in IL1ß, IL18, NFKB1 and IFNG genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953 C/T IL1ß (rs1143634), -137 G/C IL18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS-PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR = 0.58; 95% CI 0.36-0.92; p = .020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index (p = .021) and rs2430561 with DAS28 (p = .029) and CDAI (p = .029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index p < .001) and ESR (p = .034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ (F = 5.497; p < .001) and ESR (F = 2.727; p = .032)). Our analysis indicated that in the studied population +3953 C/T IL-1ß (rs1143634), -137 G/C IL-18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.
Asunto(s)
Artritis Reumatoide/diagnóstico , Predisposición Genética a la Enfermedad , Índice de Severidad de la Enfermedad , Adulto , Alelos , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Artritis Reumatoide/complicaciones , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Biomarcadores/análisis , Estudios de Casos y Controles , Evaluación de la Discapacidad , Femenino , Frecuencia de los Genes , Voluntarios Sanos , Humanos , Interferón gamma/genética , Interleucina-18/genética , Interleucina-1beta/genética , Masculino , Persona de Mediana Edad , Subunidad p50 de NF-kappa B/genética , Proyectos Piloto , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Factores Protectores , Factores de RiesgoRESUMEN
OBJECTIVE: assessing health-related quality of life (HRQL) in patients with rheumatoid arthritis (RA), before and after treatment with biological therapy. METHODS: a longitudinal study, conducted from November 2010 to September 2011, with implementation of the instruments HAQ II (health assessment questionnaire) and SF-36 (medical outcomes short-from health survey). Barlett test, Anova, Friedman and paired t-test were performed for multiple extracts. RESULTS: 30 patients were evaluated, mean age of 47.6 (SD: 12.25) years and prevalence of females (90%). The mean score of HAQ II before treatment was 1.97, with significant reduction of up to 1.23 after six months of biological therapy (p<0.01). Most of the SF-36 domains showed significant improvement after six months of treatment (p<0.01), highlighting the social aspects, pain, physical functioning, emotional issues, vitality and physical aspects. CONCLUSION: the use of biologic therapy in patients with RA refractory to standard therapies proved to be an important pharmacological strategy for improving HRQL.
Asunto(s)
Artritis Reumatoide/terapia , Terapia Biológica , Calidad de Vida , Adulto , Brasil , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Summary Objective: assessing health-related quality of life (HRQL) in patients with rheumatoid arthritis (RA), before and after treatment with biological therapy. Methods: a longitudinal study, conducted from November 2010 to September 2011, with implementation of the instruments HAQ II (health assessment questionnaire) and SF-36 (medical outcomes short-from health survey). Barlett test, Anova, Friedman and paired t-test were performed for multiple extracts. Results: 30 patients were evaluated, mean age of 47.6 (SD: 12.25) years and prevalence of females (90%). The mean score of HAQ II before treatment was 1.97, with significant reduction of up to 1.23 after six months of biological therapy (p<0.01). Most of the SF-36 domains showed significant improvement after six months of treatment (p<0.01), highlighting the social aspects, pain, physical functioning, emotional issues, vitality and physical aspects. Conclusion: the use of biologic therapy in patients with RA refractory to standard therapies proved to be an important pharmacological strategy for improving HRQL. .
Resumo Objetivo: avaliar a qualidade de vida relacionada à saúde (QVRS) em portadores de artrite reumatoide (AR), antes e após o tratamento com terapia biológica. Métodos: estudo longitudinal, realizado no período de novembro de 2010 a setembro de 2011, com aplicação dos instrumentos HAQ II (Health Assessment Questionnaire) e SF-36 (Medical Outcomes Short-From Health Survey). Foram realizados testes de Barlett, Anova, Friedman e teste- t pareado para múltiplos extratos. Resultados: foram avaliados 30 pacientes, com idade média de 47,6 (DP: 12,25) anos e prevalência do gênero feminino (90%). A média do escore do HAQ II antes do tratamento foi de 1,97, com diminuição significativa de até 1,23 após seis meses de uso de terapia biológica (p<0,01). A maioria dos domínios do SF-36 apresentou significativa melhora após seis meses de tratamento (p< 0,01), destacando os aspectos sociais, dor, capacidade funcional, aspectos emocionais, vitalidade e aspectos físicos. Conclusão: o uso de terapia biológica em pacientes com AR, refratários aos tratamentos tradicionais, demonstrou ser uma importante estratégia farmacológica para a melhoria da QVRS. .