Toll-like receptors in cellular subsets of human tonsil T cells: altered expression during recurrent tonsillitis

BACKGROUND: The palatine tonsils have a pivotal role in immunological detection of airborne and ingested antigens like bacteria and viruses. They have recently been demonstrated to express Toll-like receptors (TLRs), known to recognize molecular structures on such microbes and activate innate immune responses. Their activation might also provide a link between innate and adaptive immunity. In the present study, the expression profile of TLR1-TLR10 was characterized in human tonsil T cells, focusing on differences between subsets of CD4(+ )T helper (Th) cells and CD8(+ )cytotoxic T lymphocytes (CTL). The study was also designed to compare the TLR expression in T cells from patients with recurrent tonsillitis and tonsillar hyperplasia. METHODS: Tonsils were obtained from children undergoing tonsillectomy, and classified according to the clinical diagnoses and the outcome of tonsillar core culture tests. Two groups were defined; recurrently infected tonsils and hyperplastic tonsils that served as controls. Subsets of T cells were isolated using magnetic beads. The expression of TLR transcripts in purified cells was assessed using quantitative real-time RT-PCR. The corresponding protein expression was investigated using flow cytometry and immunohistochemistry. RESULTS: T cells expressed a broad repertoire of TLRs, in which TLR1, TLR2, TLR5, TLR9 and TLR10 predominated. Also, a differential expression of TLRs in CD4(+ )and CD8(+ )T cells was obtained. TLR1 and TLR9 mRNA was expressed to a greater extent in CD4(+ )cells, whereas expression of TLR3 mRNA and protein and TLR4 protein was higher in CD8(+ )cells. CD8(+ )cells from infected tonsils expressed higher levels of TLR2, TLR3 and TLR5 compared to control. In contrast, CD4(+ )cells exhibited a down-regulated TLR9 as a consequence of infection. CONCLUSION: The present study demonstrates the presence of a broad repertoire of TLRs in T cells, a differential expression in CD4(+ )and CD8(+ )cells, along with infection-dependent alterations in TLR expression. Collectively, these results support the idea that TLRs are of importance to adaptive immune cells. It might be that TLRs have a direct role in adaptive immune reactions against infections. Thus, further functional studies of the relevance of TLR stimulation on T cells will be of importance

Respiratory viral pathogens among Singapore military servicemen 2009 - 2012: Epidemiology and clinical characteristics

10.1186/1471-2334-14-204BMC Infectious Diseases141-BIDM

Efficacy and safety of tocilizumab in a real-life observational cohort of patients with polyarticular juvenile idiopathic arthritis

Abstract Objectives: To evaluate the patterns of usage, efficacy and safety of tocilizumab in polyarticular JIA. Methods: An observational study of 56 consecutive polyarticular JIA patients was conducted using patient charts and electronic JIA databases. Efficacy was assessed by tocilizumab survival, rates of low disease activity (LDA) and of inactive disease by 10-joint Juvenile Arthritis Disease Activity Score (JADAS-10), and of clinically inactive disease according to Wallace’s preliminary criteria. Efficacy and rate of adverse events (AEs) were evaluated during a 24-month period after tocilizumab commencement. Results: Tocilizumab was started on average as third-line biological agent (median, range first- to fourth-line) at a median disease duration of 5.2 years (interquartile range 3.0–7.7). Survival rates were 82% at 12 months and 64% at 24 months. The reasons for discontinuation were inadequate treatment effect in 50%, AE plus inadequate treatment effect in 37.5% and AE alone in 12.5%. LDA (JADAS-10 ⩽3.9) was reached in 58% at 12 months and in 84% at 24 months, inactive disease (JADAS-10 ⩽0.7) in 19% and 44%, and clinically inactive disease in 28% and 46%, respectively. The rate of AEs was 200.9/100 patient years and of serious AEs 12.9/100 patient years. Conclusion: Survival of tocilizumab was high and a large proportion of the treatment-resistant patients reached LDA at 12 months of treatment. The LDA rate continued to increase throughout 24 months. The rates of AEs and serious AEs were higher than in register studies but lower than in the originator study of tocilizumab

Defining new clinically derived criteria for high disease activity in non-systemic juvenile idiopathic arthritis:a Finnish multicentre study

Abstract Objectives: To redefine criteria for high disease activity (HDA) in JIA, to establish HDA cut-off values for the 10-joint Juvenile Arthritis Disease Activity Score (JADAS10) and clinical JADAS10 (cJADAS10) and to describe the distribution of patients’ disease activity levels based on the JADAS cut-off values in the literature. Methods: Data on 305 treatment-naïve JIA patients were collected from nine paediatric units treating JIA. The median parameters of the JADAS were proposed to be the clinical criteria for HDA. The cut-off values were assessed by using two receiver operating characteristics curve–based methods. The patients were divided into disease activity levels based on currently used JADAS cut-off values. Results: We proposed new criteria for HDA. At least three of the following criteria must be satisfied in both disease courses: in oligoarthritis, two or more active joints, ESR above normal, physician global assessment (PGA) of disease activity ≥2 and parent/patient global assessment (PtGA) of well-being ≥2; in polyarthritis, six or more active joints, ESR above normal, PGA of overall disease activity ≥4 and PtGA of well-being ≥2. The HDA cut-off values for JADAS10 (cJADAS) were ≥6.7 (6.7) for oligoarticular and ≥15.3 (14.1) for polyarticular disease. The distribution of the disease activity levels based on the JADAS cut-off values in the literature varied markedly based on which cut-offs were used. Conclusion: New clinically derived criteria for HDA in JIA and both JADAS and cJADAS cut-off values for HDA were proposed