Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter

PURPOSE: Myeloid differentiation-2 (MD-2) has been associated with endotoxin and inflammatory disorders because it can recognize lipopolysaccharide (LPS) binding and attenuate Toll-like receptor 4 (TLR4)-mediated signaling. However, its role in allergic inflammation has yet to be clarified. We examined whether single nucleotide polymorphisms (SNPs) in MD-2 promoter can affect MD-2 expression and aimed to clarify the relationship between Der p 2 allergy and SNPs of MD-2 promoter. METHODS: The function of SNPs of MD-2 promoter and the effects of cytokines and immunoglobulin on the secretion and mRNA expression were investigated in 73 allergic subjects with different MD-2 gene promoter variants. Peripheral blood mononuclear cells were cultured with or without LPS in the presence of Dermatophagoides pteronyssinus group 2 allergen (Der p 2), followed by mRNA extraction and cytokine expression analysis. The culture supernatants were collected for cytokine measurement. RESULTS: Patients with the MD-2 promoter SNPs (rs1809441/rs1809442) had increased mRNA expressions of MD-2, epsilon heavy chain of IgE (Cepsilon), and interleukin (IL)-8; however, only MD-2 and IL-8 were further up-regulated after Der p 2 stimulation. Patients with SNPs of MD-2 promoter tended to have high levels of IL-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha after Der p 2 and LPS stimulation. Increased secretions of IL-6, IL-8, and IL-10 were found to be up-regulated by Der p 2 stimulation, and an increased secretion of IFN-gamma and decreased secretion of IL-4 were noted after LPS stimulation. CONCLUSIONS: The high levels of proinflammatory cytokines secreted by Der p 2 were predetermined by MD-2 promoter SNPs (rs1809441/rs1809442). Through cytokine secretion by Der p 2 and LPS, these SNPs may serve as an indicator of the pathological phenotype of Der p 2-induced allergic inflammation.

House dust mite allergy: environment evaluation and disease prevention

There are two groups of dust mites, house dust mites (HDMs) and storage mites (SMs), that have been identified in the household environment. Both could induce airway inflammation through activation of innate and adaptive immunity and lead to asthma. In order to monitor environmental dust mite infestation, different methods can be used to detect their presence, such as the use of floating methods, monoclonal antibodies, and nanostructured biosensor. SM could be identified in the storage room, mainly in contaminated food such as mushrooms and corn starch. In HDM-sensitive subjects and mice that were challenged with HDM or SM after sensitization, these mites could up-regulate IgE levels, T helper 2 associated cytokine production and airway hypersensitivity. Different age groups of subjects were sensitized by different species of mites. More subjects above 70 years were sensitized by SM and more subjects below the age of 40 years were sensitized to HDM. Different allergenic components of dust mite extracts, such as Der p 1, Der p 2, could activate innate immunity through activating pattern recognition receptor (PRR) and then lead to allergic inflammation. The best modality to treat HDM allergy is immunomodulation through Treg cells and IgA production. In the recent years, many studies indicated probiotics could increase IgA secretion and the number of Treg cells. However, some studies conducted in adults have contradictory effects in reducing allergic symptoms. Therefore, probiotics confer inconclusive benefits on the allergic symptoms.

Nuclear matrix protein 22 and urinary cytology test in the diagnosis of bladder cancer: a meta-analysis / 中华外科杂志

<p><b>OBJECTIVE</b>Systematic reviews of diagnostic value of the nuclear matrix protein 22 (NMP22) and urine cytology for bladder cancer.</p><p><b>METHODS</b>Development of inclusion criteria, exclusion criteria and search strategy to retrieve relevant literature. Screening the literature according to inclusion criteria and exclusion criteria. Quality evaluation of the screening and data extraction, using MetaDiSc 1.4 software for Meta analysis.</p><p><b>RESULTS</b>In total, 266 relevant studies were searched, excluded 256 studies, and then 10 studies were included, with 4895 patients involved. The pooled sensitivity and specificity of NMP22 to detect bladder cancer were 0.76 (95%CI: 0.74 - 0.77), 0.80 (95%CI: 0.79 - 0.82), respectively. The pooled sensitivity and specificity of urine cytology were 0.36 (95%CI: 0.34 - 0.38), 0.94 (95%CI: 0.93 - 0.95), respectively. The area under curve (AUC) for NMP22 and urine cytology were 0.8533 and 0.8628, and Q(*) index were 0.7863 and 0.7934, respectively.</p><p><b>CONCLUSIONS</b>For the diagnosis of bladder cancer, the sensitivity of NMP22 was higher than urine cytology, but the specificity was lower than urine cytology. Overall diagnostic performance of NMP22 was medium, it was no significant difference with urine cytology. It can't replace urine cytology now.</p>