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.

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

BACKGROUND: The 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 METHODS: From 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). RESULTS: LCA 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%. CONCLUSION: Based 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.

Antibodies to hepatitis C and other viral markersin multi-transfused patients from Argentina.

BACKGROUND: The knowledge of transfusion-transmitted viral infections in Argentina is scarce. A regional study organized by the Pan American Health Organization let us asses the current status. OBJECTIVES: To estimate the prevalence of HCV, HBV and HIV infection in a population of multi-transfused Argentinean patients. STUDY DESIGN: Multi-center, cross sectional study of 504 patients from national referral institutions in Buenos Aires, who had received more than ten units of blood products in more than two occasions. Demographic and clinical data were collected using a standardized questionnaire. Blood samples were analyzed for a-HCV, a-HIV, HBsAg and a-HBcore. RESULTS: Patients belonged to five diagnostic categories: onco-hematology (309; 61.3%); hemophilia (96; 19%); acute blood loss (54; 10.7% ); hemoglobinopathies (35; 6.9%); and hemodialysis (5; 1% ); five patients (1%) had two of the previous conditions. Overall prevalence rates of viral markers were: a-HCV 9.3% (CI(95%): 6.7-12.0); a-HBcore 4.8% (CI(95): 2.8-6.7); a-HIV 1.2% (CI(95%): 0.14-2.2) and HBsAg 0.20%(CI(95%): 0.2-0.59). The highest prevalence rates were found among patients living with hemophilia (PLH). There was a significant statistical association (p < 10(-5), OR =78.8 [29.7-209.7]) between a-HCV infection and having been transfused before 1993, when screening blood donors for a-HCV became mandatory in our country. The subpopulation of patients exposed to transfusion before 1993 was conformed mostly by PLH (70.9%) and hemoglobinopathies (18.6%). In this subpopulation, we found a significant association (p < 10(Dot;), OR -40 [5.68-281.66]) between years of exposure to transfusion and a-HCV among the patients under the median age (21.95 years old); however, there was no association for those above the median age (p=0.111). CONCLUSION: a-HCV was found to be the most prevalent infection in the multi-transfused patient population under study. Most infected individuals were PLH, transfused before 1993. This study will provide support for further research aimed at improving blood safety in Argentina.

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.

La Medicina Basada en la Evidencia, un desafío para la Medicina Transfusional / Evidence-based medicine: a challenge for transfusion medicine

El objetivo de este artículo es el de presentar los pasos fundamentales para la incorporación a la práctica clínica de los conceptos de la Medicina Basada en la Evidencia (MBE). La MBE se define como "el uso consciente y juicioso de la mejor evidencia disponible en la toma de decisiones sobre el cuidado de los pacientes individuales". El ejercicio de la práctica clínica debe unir los conocimientos, habilidades y actitudes provenientes de la experiencia clínica, con la capacidad de evaluar críticamente las mejores evidencias externas disponibles provenientes de la investigación científica. El espectacular crecimiento en el volumen de la información científica y técnica publicada hace que resulte difícil discriminar e identificar la información de mayor calidad. La práctica de la MBE proporciona herramientas para: 1) poder mantenerse actualizado frente a la creciente disponibilidad de información; 2) seleccionar eficientemente las mejores fuentes de información; 3) evaluar críticamente la información disponible; 4) resumir las evidencias encontradas; y 5) integrar dicha evidencia y la experiencia, en el manejo de los problemas de los pacientes. Resulta apropiado que los Servicios de Medicina Transfusional en nuestro país reconozcamos las ventajas de juzgar críticamente la calidad de la información disponible para tomar decisiones más eficientes y con el mínimo grado de incertidumbre.