- Email: [email protected]
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Abstracts / Human Immunology 74 (2013) 51–173
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SUSCEPTIBILITY OF GENETIC POLYMORPHISM IN TOLL-LIKE RECEPTORS 2, 4 AND 9 TO AMOEBIC LIVER ABSCESS IN MEXICAN POPULATION. Oswaldo Partida-Rodriguez 1, Eric G. Hernandez 1, Carmen Maldonado 2, Olivia Valenzuela 3, Ulises J.C. Magaña 3, Edgar Rascón 3, Miriam E. Nieves-Ramirez 1, Alicia Valadez 1, Valeria Zermeño 1, Rene Cerritos 1, Tobias Portillo 1, Liliana Rojas 1, Enrique Gonzalez 1, Patricia Moran 1, Cecilia Ximenez 1. 1 Department of Experimental Medicine, National Autonomous University of Mexico, Mexico City, Mexico; 2 Laboratory of Hematology, Children’s Hospital of Mexico Federico Gomez, Mexico City, Mexico; 3 Department of Chemistry and Biological Sciences, University of Sonora, Hermosillo, Sonora, Mexico. Aim: Toll-Like Receptors (TLRs) recognize Entamoeba histolytica molecular patterns generating a series of intracellular signaling that leads to the modulation of the innate immune system. Single nucleotide polymorphisms (SNPs) in TLR genes may influence their activity. We studied associations of TLRs SNPs with susceptibility to develop amoebic liver abscess (ALA) by Entamoeba histolytica in Mexican individuals from the State of Sonora and from Mexico City (DF). Methods: We typed by allelic exclusion the SNPs R677W and R753Q of TLR2, D299G and T399I of TLR4, and -1237T/C and 2848G/A of TLR9. We compared SNPs frequencies of ALA patients (Sonora n=32, DF n=32) with control individuals (Sonora n=58, DF n=21). Results: The genotype TLR9 2848G/A in ALA patients from DF showed a statistically (p=0.008) increased frequency (63.3%) when compared with controls (25.0%), with an OR of 5.18 (95% CI 1.27-22.37). Conclusions: We will increase sample size in order to find out if the TLR9 2848G/A can be considered as a marker of susceptibility to ALA in population from the center of Mexico. Work partially supported by PAPIIT IN206408, IN206405, PAPIME 200105 and SEP-CONACYT 79220.
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TYPING AMBIGUITY SCORE – A STANDARDIZED MEASURE FOR EVALUATING AMBIGUITY IN HLA TYPING. Vanja Paunic, Loren Gragert, Joel Schneider, Chaitanya Ambadipudi, Martin Maiers. Bioinformatics Research, National Marrow Donor Program, Minneapolis, MN, USA. Aim: We previously showed that Shannon’s entropy could be successfully used to quantify the typing resolution of HLA data in stem cell registries. Here, we present an improvement of this measure, termed typing ambiguity score, which enables direct and systematic comparison across methods, data sets and populations. Methods: Typing ambiguity score is calculated from normalized Shannon’s entropy. It ranges between 0 and 1, where 1 is given to a typing with no ambiguity and 0 to a typing with maximum ambiguity. We differentiate between ambiguity in (phased) HLA genotypes and ambiguity in un-phased genotypes, which has a more practical application for donor and patient matching. Furthermore, we implement a web-based typing ambiguity assessment tool, integrated with an existing application called HaploStats that facilitates access to HLA haplotype frequencies. Results: Maximum ambiguity is obtained for a typing that results in equally probable set of outcomes, since for such cases we have the least information on what the true outcome is. For example, outcome with probabilities p = (0.5, 0.5) has a score equal to 1, while outcome with probabilities p = (0.95, 0.05) has a score of 0.28. To demonstrate how this score can be used to evaluate typings in a stem cell registry, we compute overall and per-locus ambiguity scores for HLA typings in the BeTheMatchÒ (US) registry, and explore how it varies with data resolution, typing method, time, and population. Conclusions: We present a method to objectively quantify and compare ambiguity in HLA typing data obtained via different methods. An analysis of HLA typing data in the US registry demonstrates the utility of this method for stem cell registries and HLA typing labs. We show that the typing ambiguity score can compare typing methodologies, determine which methods are best suited for which populations, and help define acceptable HLA typing for donor recruitment.
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SUSCEPTIBILITY OF GENETIC POLYMORPHISM IN TOLL-LIKE RECEPTORS 2, 4 AND 9 TO AMOEBIC LIVER ABSCESS IN MEXICAN POPULATION. Oswaldo Partida-Rodriguez 1, Eric G. Hernandez 1, Carmen Maldonado 2, Olivia Valenzuela 3, Ulises J.C. Magaña 3, Edgar Rascón 3, Miriam E. Nieves-Ramirez 1, Alicia Valadez 1, Valeria Zermeño 1, Rene Cerritos 1, Tobias Portillo 1, Liliana Rojas 1, Enrique Gonzalez 1, Patricia Moran 1, Cecilia Ximenez 1. 1 Department of Experimental Medicine, National Autonomous University of Mexico, Mexico City, Mexico; 2 Laboratory of Hematology, Children’s Hospital of Mexico Federico Gomez, Mexico City, Mexico; 3 Department of Chemistry and Biological Sciences, University of Sonora, Hermosillo, Sonora, Mexico. Aim: Toll-Like Receptors (TLRs) recognize Entamoeba histolytica molecular patterns generating a series of intracellular signaling that leads to the modulation of the innate immune system. Single nucleotide polymorphisms (SNPs) in TLR genes may influence their activity. We studied associations of TLRs SNPs with susceptibility to develop amoebic liver abscess (ALA) by Entamoeba histolytica in Mexican individuals from the State of Sonora and from Mexico City (DF). Methods: We typed by allelic exclusion the SNPs R677W and R753Q of TLR2, D299G and T399I of TLR4, and -1237T/C and 2848G/A of TLR9. We compared SNPs frequencies of ALA patients (Sonora n=32, DF n=32) with control individuals (Sonora n=58, DF n=21). Results: The genotype TLR9 2848G/A in ALA patients from DF showed a statistically (p=0.008) increased frequency (63.3%) when compared with controls (25.0%), with an OR of 5.18 (95% CI 1.27-22.37). Conclusions: We will increase sample size in order to find out if the TLR9 2848G/A can be considered as a marker of susceptibility to ALA in population from the center of Mexico. Work partially supported by PAPIIT IN206408, IN206405, PAPIME 200105 and SEP-CONACYT 79220.
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TYPING AMBIGUITY SCORE – A STANDARDIZED MEASURE FOR EVALUATING AMBIGUITY IN HLA TYPING. Vanja Paunic, Loren Gragert, Joel Schneider, Chaitanya Ambadipudi, Martin Maiers. Bioinformatics Research, National Marrow Donor Program, Minneapolis, MN, USA. Aim: We previously showed that Shannon’s entropy could be successfully used to quantify the typing resolution of HLA data in stem cell registries. Here, we present an improvement of this measure, termed typing ambiguity score, which enables direct and systematic comparison across methods, data sets and populations. Methods: Typing ambiguity score is calculated from normalized Shannon’s entropy. It ranges between 0 and 1, where 1 is given to a typing with no ambiguity and 0 to a typing with maximum ambiguity. We differentiate between ambiguity in (phased) HLA genotypes and ambiguity in un-phased genotypes, which has a more practical application for donor and patient matching. Furthermore, we implement a web-based typing ambiguity assessment tool, integrated with an existing application called HaploStats that facilitates access to HLA haplotype frequencies. Results: Maximum ambiguity is obtained for a typing that results in equally probable set of outcomes, since for such cases we have the least information on what the true outcome is. For example, outcome with probabilities p = (0.5, 0.5) has a score equal to 1, while outcome with probabilities p = (0.95, 0.05) has a score of 0.28. To demonstrate how this score can be used to evaluate typings in a stem cell registry, we compute overall and per-locus ambiguity scores for HLA typings in the BeTheMatchÒ (US) registry, and explore how it varies with data resolution, typing method, time, and population. Conclusions: We present a method to objectively quantify and compare ambiguity in HLA typing data obtained via different methods. An analysis of HLA typing data in the US registry demonstrates the utility of this method for stem cell registries and HLA typing labs. We show that the typing ambiguity score can compare typing methodologies, determine which methods are best suited for which populations, and help define acceptable HLA typing for donor recruitment.
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