Clinical characteristics and frequency of TLR4 polymorphisms in Brazilian patients with ankylosing spondylitis / Características clínicas e frequência de polimorfismos em TLR4 em pacientes brasileiros com espondilite anquilosante

ABSTRACT Objectives: Innate immunity is involved in the physiopathology of ankylosing spondylitis (AS), with the participation of Gram-negative bacteria, modulation of human leukocyte antigen (HLA) B27 and the involvement of pattern recognition receptors, such as Toll-like receptors (TLRs). The aim of this study was to investigate the clinical characteristics and frequency of TLR4 polymorphisms (Asp299Gly and Thr 399Ile) in a cohort of Brazilian patients with AS. Methods: A cross-sectional study was carried out involving 200 patients with a diagnosis of AS and a healthy control group of 200 individuals. Disease activity, severity and functional capacity were measured. The study of TLR4 polymorphisms was performed using the restriction fragment length polymorphism method. HLA-B27 was analyzed by conventional polymerase chain reaction. The IBM SPSS Statistics 20 program was used for the statistical analysis, with p-values less than 0.05 considered significant. Results: Mean age and disease duration were 43.1 ± 12.7 and 16.6 ± 9.2 years, respectively. The sample was predominantly male (71%) and non-Caucasian (52%). A total of 66% of the group of patients were positive for HLA-B27. The sample of patients was characterized by moderate functional impairment and a high degree of disease activity. No significant association was found between the two TLR4 polymorphisms and susceptibility to AS. Conclusions: TLR4 polymorphisms 399 and 299 were not more frequent in patients with AS in comparison to the health controls and none of the clinical variables were associated with these polymorphisms.

RESUMO Objetivos: A imunidade inata está envolvida na fisiopatologia da espondilite anquilosante (EA), com a participação de bactérias gram-negativas, modulação do antígeno leucocitário humano (HLA) B27 e o envolvimento de receptores de reconhecimento de padrões, como os receptores Toll-like (TLR). O objetivo deste estudo foi investigar as características clínicas e a frequência de polimorfismos em TLR4 (Asp299Gly e Thr399Ile) em uma coorte de pacientes brasileiros com EA. Métodos: Fez-se um estudo transversal que envolveu 200 pacientes com diagnóstico de EA e um grupo controle saudável de 200 indivíduos. Mediram-se a atividade da doença, a gravidade e a capacidade funcional. O estudo dos polimorfismos em TLR4 foi feito com o método de polimorfismo de fragmentos de restrição. O HLA-B27 foi analisado por reação em cadeia da polimerase convencional. Usou-se o programa SPSS Statistics 20 da IBM para a análise estatística e foram considerados significativos valores de p inferiores a 0,05. Resultados: A média de idade e a duração da doença foram de 43,1 ± 12,7 e 16,6 ± 9,2 anos, respectivamente. A amostra foi predominantemente do sexo masculino (71%) e de não brancos (52%). Do grupo de pacientes 66% eram HLA-B27 positivos. A amostra de pacientes foi caracterizada por uma alteração funcional moderada e um elevado grau de atividade da doença. Não foi encontrada associação estatisticamente significativa entre os polimorfismos em TLR4 e a susceptibilidade à EA. Conclusões: Os polimorfismos em TLR4 399 e 299 não foram mais frequentes em pacientes com EA em comparação com controles saudáveis e nenhuma das variáveis clínicas esteve associada a esses polimorfismos.

Late recognition and illness severity are determinants of early death in severe septic patients

OBJECTIVE: To identify the independent variables associated with death within 4 days after the first sepsis-induced organ dysfunction. METHODS: In this prospective observational study, severe sepsis and septic shock patients were classified into 3 groups: Group 1, survivors; Group 2, late non-survivors; and Group 3, early non-survivors. Early death was defined as death occurring within 4 days after the first sepsis-induced organ dysfunction. Demographic, clinical and laboratory data were collected and submitted to univariate and multinomial analyses. RESULTS: The study included 414 patients: 218 (52.7%) in Group 1, 165 (39.8%) in Group 2, and 31 (7.5%) in Group 3. A multinomial logistic regression analysis showed that age, Acute Physiology and Chronic Health Evaluation II score, Sepsis-related Organ Failure Assessment score after the first 24 hours, nosocomial infection, hepatic dysfunction, and the time elapsed between the onset of organ dysfunction and the sepsis diagnosis were associated with early mortality. In contrast, Black race and a source of infection other than the urinary tract were associated with late death. Among the non-survivors, early death was associated with Acute Physiology and Chronic Health Evaluation II score, chronic renal failure, hepatic dysfunction Sepsis-related Organ Failure Assessment score after 24 hours, and the duration of organ dysfunction. CONCLUSION: Factors related to patients' intrinsic characteristics and disease severity as well as the promptness of sepsis recognition are associated with early death among severe septic patients. .