HLA-DRB1 association with Henoch-Schonlein purpura

Objective: Henoch-Schönlein purpura (HSP) is the most common vasculitis in children but it is not exceptional in adults. Increased familial occurrence supports a genetic predisposition for HSP. In this context, an association with the human leukocyte antigen-HLA-DRB1*01 phenotype has been suggested in Caucasian individuals with HSP. However, data on the potential association of HSP with HLA-DRB1*01 were based on small case series. To further investigate this issue, we performed HLA-DRB1 genotyping of the largest series of HSP patients ever assessed for genetic studies in Caucasians. Methods: 342 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al classification criteria, and 303 sex and ethnically matched controls were assessed. HLA-DRB1 alleles were determined using a PCR-Sequence-Specific-Oligonucleotide Probe (PCR-SSOP) method. Results: A statistically significant increase of HLA-DRB1*01 in HSP patients when compared with controls was found (43% vs 7%, respectively; p<0.001; odds ratio-OR=2.03 [1.43-2.87]). It was due to the increased frequency of HLA-DRB1*0103 phenotype in HSP (14% vs 2%; p<0.001; OR=8.27 [3.46-23.9]). These results remained statistically significant after adjusting for Bonferroni correction. In contrast, a statistically significant decreased frequency of the HLA-DRB1*0301 phenotype was observed in patients compared to controls (5.6% vs 18.1%, respectively; p<0.001, OR=0.26 [0.14-0.47]), even after adjustment for Bonferroni correction. No HLA-DRB1 association with specific features of the disease was found. Conclusion: Our study confirms an association of HSP with HLA-DRB1*01 in Caucasians. Also, a protective effect against the development of HSP appears to exist in Caucasians carrying the HLA-DRB1*03 phenotype

A Novel Therapy for Melanoma Developed in Mice: Transformation of Melanoma into Dendritic Cells with Listeria monocytogenes

Listeria monocytogenes is a gram-positive bacteria and human pathogen widely used in cancer immunotherapy because of its capacity to induce a specific cytotoxic T cell response in tumours. This bacterial pathogen strongly induces innate and specific immunity with the potential to overcome tumour induced tolerance and weak immunogenicity. Here, we propose a Listeria based vaccination for melanoma based in its tropism for these tumour cells and its ability to transform in vitro and in vivo melanoma cells into matured and activated dendritic cells with competent microbicidal and antigen processing abilities. This Listeria based vaccination using low doses of the pathogen caused melanoma regression by apoptosis as well as bacterial clearance. Vaccination efficacy is LLO dependent and implies the reduction of LLO-specific CD4+ T cell responses, strong stimulation of innate pro-inflammatory immune cells and a prevalence of LLO-specific CD8+ T cells involved in tumour regression and Listeria elimination. These results support the use of low doses of pathogenic Listeria as safe melanoma therapeutic vaccines that do not require antibiotics for bacterial removal

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Evolutionary history of the Azteca-like mariner transposons and their host ants

Three different complete mariner elements were found in the genome of the ant Tapinoma nigerrimum. One (Tnigmar-Mr) was interrupted by a 900-bp insertion that corresponded to an incomplete member of a fourth mariner element, called Azteca. In this work, we isolate and characterize full-length Tnigmar-Az elements in T. nigerrimum. The purpose of this study is to clarify the evolutionary history of Azteca elements and their hosts as well as the possible existence of horizontal transfer processes. For this, Azteca-like elements were also retrieved from the available sequences of various ant genomes, representing four different ant subfam-ilies: Dolichoderinae, Formicinae, Myrmicinae, and Ponerinae. The tree topology resulting for the Azteca-like elements bore very little resemblance to that of their respective hosts. The pervasive presence of Azteca-like elements in all ant genomes, together with the observation that extant copies are usually younger than the genomes that host them, could be explained either by lineage sorting or by recent horizontal transfer of active elements. However, the finding of closer genetic relationships between elements than between the ants that host them is consistent with the latter scenario. This is clearly observed in Sinvmar-Az, Tnigmar-Az, Acepmar-Az, and Cflomar-Az elements, suggesting the existence of horizontal transfer processes. On the contrary, some elements displayed more divergence than did the hosts harboring them. This may reflect either further horizontal transfer events or random lineage sorting