HLA DQA1*05 and DQB1*02 alleles encoding the DQ2.5 molecule and HLA DQA1*03 and DQB1*03 alleles encoding DQ8 molecules are strongly associated with celiac disease (CD) and type 1 diabetes (T1D), two common autoimmune diseases (AD). We previously demonstrated that DQ2.5 genes showed a higher expression with respect to non-CD associated alleles in heterozygous DQ2.5 positive (HLA DR1/DR3) antigen presenting cells (APC) of CD patients. This differential expression affected the level of the encoded DQ2.5 molecules on the APC surface and established the strength of gluten-specific CD4+ T cells response. Here, we expanded the expression analysis of risk alleles in patients affected by T1D or by T1D and CD comorbidity. In agreement with previous findings, we found that DQ2.5 and DQ8 risk alleles are more expressed than non-associated alleles also in T1D patients and favor the self-antigen presentation. To investigate the mechanism causing the high expression of risk alleles, we focused on HLA DQA1*05 and DQB1*02 alleles and, by ectopic expression of a single mRNA, we modified the quantitative equilibrium among the two transcripts. After transfection of DR7/DR14 B-LCL with HLA-DQA1*05 cDNA, we observed an overexpression of the endogenous DQB1*02 allele. The DQ2.5 heterodimer synthesized was functional and able to present gluten antigens to cognate CD4+ T cells. Our results indicated that the high expression of alpha and beta transcripts, encoding for the DQ2.5 heterodimeric molecules, was strictly coordinated by a mechanism acting at a transcriptional level. These findings suggested that, in addition to the predisposing HLA-DQ genotype, also the expression of risk alleles contributed to the establishment of autoimmunity.
Background Timing and adequacy of peritoneal source control are the most important pillars in the management of patients with acute peritonitis. Therefore, early prognostic evaluation of acute peritonitis is paramount to assess the severity and establish a prompt and appropriate treatment. The objectives of this study were to identify clinical and laboratory predictors for in-hospital mortality in patients with acute peritonitis and to develop a warning score system, based on easily recognizable and assessable variables, globally accepted. Methods This worldwide multicentre observational study included 153 surgical departments across 56 countries over a 4-month study period between February 1, 2018, and May 31, 2018. Results A total of 3137 patients were included, with 1815 (57.9%) men and 1322 (42.1%) women, with a median age of 47 years (interquartile range [IQR] 28–66). The overall in-hospital mortality rate was 8.9%, with a median length of stay of 6 days (IQR 4–10). Using multivariable logistic regression, independent variables associated with in-hospital mortality were identified: age > 80 years, malignancy, severe cardiovascular disease, severe chronic kidney disease, respiratory rate ≥ 22 breaths/min, systolic blood pressure < 100 mmHg, AVPU responsiveness scale (voice and unresponsive), blood oxygen saturation level (SpO 2 ) < 90% in air, platelet count < 50,000 cells/mm3, and lactate > 4 mmol/l. These variables were used to create the PIPAS Severity Score, a bedside early warning score for patients with acute peritonitis. The overall mortality was 2.9% for patients who had scores of 0–1, 22.7% for those who had scores of 2–3, 46.8% for those who had scores of 4–5, and 86.7% for those who have scores of 7–8. Conclusions The simple PIPAS Severity Score can be used on a global level and can help clinicians to identify patients at high risk for treatment failure and mortality.
In this study native starches as ingredients (corn, rice, wheat, tapioca and potato) were characterized for microstructure, physicochemical, functional and thermal properties, in vitro digestibility and glycemic index. There was a significant variation in the granule shape and size distribution of the starches. Particle size monomodal (corn, tapioca, potato) and bimodal (rice, wheat) distribution was observed amongst the starches. The potato starch showed the biggest size granules while the rice showed the smallest. The examined properties and nutritional characteristics of starches were significantly different. Thermal properties were studied using Differential Scanning Calorimeter (DSC). DSC results showed that the transition temperatures (58.8-78.7°C) and enthalpies of gelatinization (2.3-8.2 J/ g) of the starches appeared to be greatly influenced by microstructure and chemical composition (e.g. resistant starch). Nutritional properties such as slowly digestible starch and expected glycemic index values followed the order: rice [ wheat [ tapioca [ corn [ potato. In particular, the highest resistant starch was recorded for potato starch.
Surface enhanced Raman scattering can offer rapid and label-free detailed molecular fingerprints of gingival crevicular fluid, reflecting the physiological and pathological states of a single dental element.
The DR5-DQ7/DR7-DQ2 genotype is very frequent among patients affected by celiac disease (CD), in Europe. This genotype, associated to high risk of CD, carries the HLA-DQA1*05 and HLA-DQB1*02 predisposing alleles, in trans configuration. The alleles encode the DQ2.5 heterodimer responsible of gluten peptide presentation on the surface of antigen-presenting cells (APCs), and consequent pathogenic CD4+ T cell activation. We demonstrated that DR5/DR7 APCs induce an anti-gluten CD4+ T cell response, of comparable intensity to that observed with APCs carrying DR1/DR3 genotype, which risk alleles are in cis configuration. In addition, we showed that DR5/DR7 APCs from celiac patients stimulated an effector CD4+ T cell response higher with respect to that induced by DR5/DR7 APCs from healthy subjects. To explain these findings, we assessed the DQ2.5 RNA and protein quantity. We showed that the expression of DQA1*05 and DQB1*02 risk alleles is much higher than the expression of non-CD-associated alleles, in agreement with the previous results obtained with DR1/DR3 genotype. The differential expression of transcripts influences the quantity of DQα1*05 and DQβ1*02 chains and, as consequence, the cell surface density of DQ2.5 heterodimers. Moreover, both RNA and proteins, are more abundant in APCs from celiac patients than controls. Finally, to unravel the mechanism regulating the expression of predisposing DQA1*05 and DQB1*02 alleles, we quantified the new synthetized RNA and found that the differential expression is explained by their transcription rate. Our results confirmed that the strength of antigen-specific CD4+ T cell response is mainly determined by the amount of gluten in the diet and provided a new possible approach for a personalized diagnosis and for risk stratification.
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