HLA diversity in the Argentinian Umbilical Cord Blood Bank: frequencies according to donor’s reported ancestry and geographical distribution

Umbilical cord blood (UCB) is a suitable source for hematopoietic stem cell transplantation. The study of HLA genes by next generation sequencing is commonly used in transplants. Donor/patient HLA matching is often higher within groups of common ancestry, however “Hispanic” is a broad category that fails to represent Argentina’s complex genetic admixture. Our aim is to describe HLA diversity of banked UCB units collected across the country taking into consideration donor’s reported ancestral origins as well as geographic distribution. Our results showed an evenly distribution of units mainly for 2 groups: of European and of Native American descent, each associated to a defined geographic location pattern (Central vs. North regions). We observed differences in allele frequency distributions for some alleles previously described in Amerindian populations: for Class I (A*68:17, A*02:11:01G, A*02:22:01G, B*39:05:01, B*35:21, B*40:04, B*15:04:01G, B*35:04:01, B*51:13:01) and Class II (DRB1*04:11:01, DRB1*04:07:01G/03, DRB1*08:02:01, DRB1*08:07, DRB1*09:01:02G, DRB1*14:02:01, DRB1*16:02:01G). Our database expands the current knowledge of HLA diversity in Argentinian population. Although further studies are necessary to fully comprehend HLA heterogeneity, this report should prove useful to increase the possibility of finding compatible donors for successful allogeneic transplant and to improve recruitment strategies for UCB donors across the country.Fil: Fernández Souto, Daniela. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Centro Regional de Hemoterapia; ArgentinaFil: Rosello, Julieta. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Centro Regional de Hemoterapia; ArgentinaFil: Lazo, Maria Laura. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Centro Regional de Hemoterapia; ArgentinaFil: Veloso, Florencia. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Centro Regional de Hemoterapia; ArgentinaFil: Gamba, Cecilia. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Centro Regional de Hemoterapia; ArgentinaFil: Kuperman, Silvina Laura. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Centro Regional de Hemoterapia; ArgentinaFil: Roca, Valeria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Centro Regional de Hemoterapia; Argentin

The novel RHD c.325A>G single nucleotide variation found in Argentineans leads to a partial D phenotype

One novel RHD allele was detected in the analysed population of Argentina. The missense mutation c.325A>G is responsible for the amino acidic change p.Thr109Ala, predicted to be in the extracellular boundary of the fourth transmembrane segment of the RhD protein. This new allele has been submitted to GenBank with accession number MN262645 and was designated by the ISBT as RHD*66. The polymorphism had been annotated as rs1376983227 in the GnomAD database and is present in only one African individual with an allele frequency of 0.00006424. Interestingly, the three samples harboring the aforementioned mutation showed the agglutination pattern of a DFR phenotype as indicated by the ID-Partial RhD typing set (Table 1). While the already-reported five DFR variants result from hybrid structures involving RHD Exon 4 (and also Exon 3 in DFR-5),1,2 a point mutation in RHD Exon 2 is responsible for the new allele described in this work. Serologic and molecular results suggest a genetic association in cis between this new RHD variant and the RHCE*Ce allele (Table 1). Surprisingly, the novel RHD*66 allele was found in 2.48% (3/121) of serologic weak D samples from the central area of Argentina. We can speculate that the RHD*66 allele could not be attributed to the Amerindian genetic influence as no sample from the Northwestern area-where the native contribution is higher than in other parts of the country-exhibited the c.325A>G SNV. This new variant could be related rather to the Caucasian genetic component that predominates in the central region.5 Our findings suggest that a RHD genotyping strategy for our population should consider the detection of this relatively prevalent RHD*66 allele.Fil: Mufarrege, Nicolas Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Trucco Boggione, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Puppo, Mónica. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Centro Regional de Hemoterapia; ArgentinaFil: Ensinck, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Principi, Cintia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Luján Brajovich, Melina Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Mattaloni, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Biondi, Claudia Silvia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Kuperman, Silvina Laura. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Centro Regional de Hemoterapia; ArgentinaFil: Cotorruelo, Carlos Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin

Estimation of sensitivity and specificity of several Trypanosoma cruzi antibody assays in blood donors in Argentina.

BackgroundThe absence of a gold standard test for Trypanosoma cruzi antibodies represents a problem not only for the evaluation of screening tests, but also for appropriate blood donor counseling. The aim of this study was to estimate the sensitivity and specificity of multiple blood donor screening tests for T. cruzi antibodies in Argentina.Study design and methodsFrom June 2006 to March 2007 a sample of 1455 blood donors was recruited from two blood banks in Chaco province, an area of Argentina with highly endemic T. cruzi infection. Samples were tested by three epimastigote lysate enzyme immunoassays (EIAs), one recombinant antigen EIA, two indirect hemagglutination assay (IHA) tests, a particle agglutination assay (PA), and a research trans-sialidase inhibition assay (TIA). Sensitivity and specificity were estimated using latent class analysis (LCA).ResultsLCA estimated the consensus prevalence of T. cruzi infection at 24.5%. Interassay correlation was higher among the four EIA tests and TIA compared to IHA tests. Assay sensitivities varied from 96 to 99.7 for different EIAs, 91% for TIA, 84% for PA, and 66 to 74% for IHA tests. Relative to the LCA, assay specificities were from 96% to almost 100%.ConclusionBased on the comparison of several tests in a large population from an endemic area for T. cruzi infection, our data showed an adequate sensitivity for EIA tests in contrast to PA and IHA assays. The latter tests should no longer be used for blood donor screening

Estimation of sensitivity and specificity of several Trypanosoma cruzi antibody assays in blood donors in Argentina.

BackgroundThe absence of a gold standard test for Trypanosoma cruzi antibodies represents a problem not only for the evaluation of screening tests, but also for appropriate blood donor counseling. The aim of this study was to estimate the sensitivity and specificity of multiple blood donor screening tests for T. cruzi antibodies in Argentina.Study design and methodsFrom June 2006 to March 2007 a sample of 1455 blood donors was recruited from two blood banks in Chaco province, an area of Argentina with highly endemic T. cruzi infection. Samples were tested by three epimastigote lysate enzyme immunoassays (EIAs), one recombinant antigen EIA, two indirect hemagglutination assay (IHA) tests, a particle agglutination assay (PA), and a research trans-sialidase inhibition assay (TIA). Sensitivity and specificity were estimated using latent class analysis (LCA).ResultsLCA estimated the consensus prevalence of T. cruzi infection at 24.5%. Interassay correlation was higher among the four EIA tests and TIA compared to IHA tests. Assay sensitivities varied from 96 to 99.7 for different EIAs, 91% for TIA, 84% for PA, and 66 to 74% for IHA tests. Relative to the LCA, assay specificities were from 96% to almost 100%.ConclusionBased on the comparison of several tests in a large population from an endemic area for T. cruzi infection, our data showed an adequate sensitivity for EIA tests in contrast to PA and IHA assays. The latter tests should no longer be used for blood donor screening

A polymorphism in TIM1 is associated with susceptibility to severe hepatitis A virus infection in humans

During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy

Prácticas pedagógicas y políticas educativas : investigaciones en el territorio bonaerense

Prácticas pedagógicas y políticas educativas. Investigaciones en el territorio bonaerense es la primera publicación en forma de libro que reúne producciones de los equipos de investigación y docencia de la Universidad Pedagógica, validadas académicamente por pares externos oficialmente reconocidos. Este libro expresa la potencialidad de concebir un modelo formativo que revierta la histórica escisión entre docencia e investigación y de concretarlo en una institución universitaria. Por diversos motivos, las visiones paradigmáticas que signaron la formación docente excluyeron la investigación como uno de sus pilares. Un modelo universitario como el que la UNIPE se propone implica que los docentes y demás agentes educativos construyan una actitud investigativa como requisito indispensable para adaptarse a condiciones sociales crecientemente cambiantes, sin perder de vista -aun en contextos de alta vulnerabilidad social y con un bajo grado de reconocimiento- el sentido formativo del trabajo colectivo en las instituciones educativas. La formación docente constituye el eje vertebrador de todos los trabajos de este libro, que consideramos una primera contribución al pensamiento pedagógico entendido como aquel que interroga a la educación de la perspectiva de la formación humana