SummaryTuberculosis remains one of the most important infectious diseases worldwide. Several studies have suggested that genetic factors may affect susceptibility to tuberculosis, but the specific genes involved have not yet been fully characterized. NRAMP1/SLC11 A1 and P2X7 genes have been linked to increased risk for tuberculosis in some African and Asiatic populations. To explore the potential role of these genes in the susceptibility to pulmonary tuberculosis in a Mexican mestizo population, we evaluated the association of D543N and 3Ј-UTR polymorphisms in NRAMP1/SLC11 A1 and -762 and A1513C polymorphisms in P2X7 genes with the risk for tuberculosis. Polymerase chain reaction (PCR) amplification of genomic DNA followed by restriction fragment length polymorphism analysis, and allelic-specific PCR was employed. We found no significant differences in allelic frequency in NRAMP1/SLC11 A1 gene polymorphisms in 94 patients with tuberculosis compared to 100 healthy contacts. Similarly, no significant association of the P2X7-762 gene polymorphism with tuberculosis was detected. In contrast, the P2X7 A1513C polymorphism was associated significantly with tuberculosis (P = 0·02, odds ratio = 5·28, 95% CI, 0·99-37·69), an association that had not been reported previously. However, when the function of P2X7 was assessed by an l-selectin loss assay, we did not find significant differences in patients compared to healthy contacts or between PPD + and PPD -control individuals. This study further supports the complex role of P2X7 gene in host regulation of Mycobacterium tuberculosis infection, and demonstrates that different associations of gene polymorphisms and tuberculosis are found in distinct racial populations.
Severe pneumonia developed in young adults who had no identifiable risk factors.
Background:To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU).Methods:Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009).Results:We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses.Conclusions:Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.
Introduction of a novel influenza virus into the human population leads to the occurrence of pandemic events, such as the one caused by pandemic influenza A (H1N1) 2009 virus. The severity of infections caused by this virus in young adults was greater than that observed in patients with seasonal influenza. Fatal cases have been associated with an abnormal innate, proinflammatory immune response. A critical role for natural killer cells during the initial responses to influenza infections has been suggested. In this study, we assessed the association of killer-cell immunoglobulin-like receptors (KIRs) with disease severity by comparing KIR gene content in patients with mild and severe pandemic influenza virus infections to a control group. We found that activator (KIR3DS1 and KIR2DS5) and inhibitory (KIR2DL5) genes, encoded in group B haplotypes containing the cB01, cB03 and tB01 motifs, are associated with severe pandemic influenza A (H1N1) 2009 infections. Better understanding of how genetic variability contributes to influenza virus pathogenesis may help to the development of immune intervention strategies aiming at controlling the severity of disease.
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