Pharmacogenetics: ethnicity, treatment and health in Latin American populations.

The Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF) studies Latin American populations to benefit from the implementation of personalized medicine. Since 2006, it has studied ethnicity to apply pharmacogenetics knowledge in autochthonous populations of Latin America, considering ancestral medicine. The meeting 'Pharmacogenetics: ethnicity, Treatment and Health in Latin American Populations' was held in Mexico City, Mexico, and presented the relevance of RIBEF collaboration with Latin American researchers and the governments of Mexico, Spain and the Autonomous Community of Extremadura. The results of 17 years of uninterrupted work by RIBEF, the Declaration of Mérida/T'Hó and the call for the Dr José María Cantú Award for studies focused on the pharmacogenetics of native populations in Latin America were presented.

Interethnic Variability in CYP2D6, CYP2C9, and CYP2C19 Genes and Predicted Drug Metabolism Phenotypes Among 6060 Ibero- and Native Americans: RIBEF-CEIBA Consortium Report on Population Pharmacogenomics.

Pharmacogenetic variation in Latin Americans is understudied, which sets a barrier for the goal of global precision medicine. The RIBEF-CEIBA Network Consortium was established to characterize interindividual and between population variations in CYP2D6, CYP2C9, and CYP2C19 drug metabolizing enzyme genotypes, which were subsequently utilized to catalog their "predicted drug metabolism phenotypes" across Native American and Ibero American populations. Importantly, we report in this study, a total of 6060 healthy individuals from Ibero-America who were classified according to their self-reported ancestry: 1395 Native Americans, 2571 Admixed Latin Americans, 96 Afro-Latin Americans, 287 white Latin Americans (from Cuba), 1537 Iberians, and 174 Argentinean Ashkenazi Jews. Moreover, Native Americans were grouped into North-, Central-, and South Amerindians (from Mexico, Costa Rica, and Peru, respectively). All subjects were studied for the most common and functional CYP2D6, CYP2C9, and CYP2C19 allelic variants, and grouped as genotype-predicted poor or ultrarapid metabolizer phenotypes (gPMs and gUMs, respectively). Native Americans showed differences from each ethnic group in at least two alleles of CYP2D6, CYP2C9, and CYP2C19. Native Americans had higher frequencies of wild-type alleles for all genes, and lower frequency of CYP2D6*41, CYP2C9*2, and CYP2C19*17 (p < 0.05). Native Americans also showed less CYP2C19 gUMs than the rest of the population sample. In addition, differences within Native Americans (mostly North vs. South) were also found. The interethnic differences described supports the need for population-specific personalized and precision medicine programs for Native Americans. To the best of our knowledge, this is the largest study carried out in Native Americans and other Ibero-American populations analyzing CYP2D6, CYP2C9, and CYP2C19 genetic polymorphisms. Population pharmacogenomics is a nascent field of global health and warrants further research and education.

Pharmacogenetics and ethnicity: relevance for clinical implementation, clinical trials, pharmacovigilance and drug regulation in Latin America.

Congress of Pharmacogenetics and Personalized Medicine. Ethnicity, clinical implementation and regulatory environment (MESTIFAR 2016 Quito) Quito, Ecuador, 19-21 May 2016. The Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF) was created in 2006 with the main aim of promoting personalized medicine and collaborative pharmacogenetics research in Spanish- and Portuguese-speaking countries in America and the Iberian Peninsula. The final goal of this initiative was the inclusion of Latin American populations that may benefit from the implementation of personalized medicine in drug therapy. Several initiatives have been promoted including the MESTIFAR project, which aimed to analyze the ethnicity, genotype and/or metabolic phenotype in Ibero-American populations. To date, 6060 healthy volunteers have been analyzed; among them, 2571 were admixed, 1824 were Caucasians, 1395 were Native Americans, 174 were Jews and 96 were Afro-descendants. Due to the large genetic variability within Latin Americans, ethnicity may be a relevant factor for the clinical implementation of personalized medicine. Moreover, the present status of clinical implementation and the future perspectives of pharmacogenetics, pharmacovigilance and clinical trials for drug regulation in Latin America compared with the EMA-Pharmacogenomics Working Party and the US FDA initiatives were analyzed.

Pharmacogenetic research activity in Central America and the Caribbean: a systematic review.

AIM: The present review was aimed at analyzing the pharmacogenetic scientific activity in Central America and the Caribbean. MATERIALS & METHODS: A literature search for pharmacogenetic studies in each country of the region was conducted on three databases using a list of the most relevant pharmacogenetic biomarkers including 'phenotyping probe drugs' for major drug metabolizing enzymes. The review included 132 papers involving 47 biomarkers and 35,079 subjects (11,129 healthy volunteers and 23,950 patients). RESULTS: The country with the most intensive pharmacogenetic research was Costa Rica. The most studied medical therapeutic area was oncology, and the most investigated biomarkers were CYP2D6 and HLA-A/B. Conclusion: Research activity on pharmacogenetics in Central American and the Caribbean populations is limited or absent. Therefore, strategies to promote effective collaborations, and foster interregional initiatives and research efforts among countries from the region could help for the rational clinical implementation of pharmacogenetics and personalized medicine.

Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population / Relevancia de la ancestría para la variabilidad de polimorfismos de las enzimas metabolizadoras de fármacos CYP2C9, CYP2C19 y CYP2D6 en una población multiétnica de Costa Rica

Abstract:CYP2C9, CYP2C19 and CYP2D6 metabolize around 40 % of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry. A total of 448 healthy individuals were included in the study: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limón. CYP2C9 (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined by Real-Time PCR. African, European and Native American ancestry were inferred using 87 ancestry informative markers. The frequency of the decreased activity allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the admixed population, and the highest frequencies of CYP2C19*2 (null activity) and the CYP2C19*17 (increased activity) were found in the self-reported AfroCaribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following alleles were positively correlated with genomic African ancestry and negatively correlated with genomic Native American ancestry: CYP2D6*5 (null activity), CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17 (increased activity). No correlation for CYP2C9 polymorphisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted. Rev. Biol. Trop. 64 (3): 1067-1076. Epub 2016 September 01.

ResumenCYP2C9, CYP2C19 y CYP2D6 metabolizan aproximadamente el 40 % de los fármacos y los genes que las codifican varían en las distintas poblaciones humanas. La población costarricense posee ancestría trihíbrida y su posición geográfica estratégica la convierten en un escenario idóneo para evaluar la variabilidad interétnica en sus poblaciones multiétnicas. El presente estudio tiene como objetivo describir la diversidad de los polimorfismos CYP2C9, CYP2C19 y CYP2D6 en las poblaciones costarricenses en el contexto de su ancestría. Un total de 448 individuos sanos fueron incluidos: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), mestizos del Valle Central y Guanacaste (n= 189) y afrocaribeños de Limón (n= 50). Los genotipos CYP2C9 (alelos *2, *3, *6) y CYP2C19 (*2, *3, *4, *5 y *17) fueron determinados mediante PCR tiempo real. Las ancestrías africana, europea y nativa americana fueron inferidas usando 87 marcadores informativos de ancestría. La frecuencia del alelo de actividad disminuida CYP2C9*2 fue menor en los grupos autodefinidos de amerindios que en la población mestiza y las frecuencias más altas de CYP2C19*2 (actividad nula) y CYP2C19*17 (actividad incrementada) se encontraron en la población autodefinida afrocaribeña. Asimismo, se encontró una frecuencia de gPMs CYP2C9 de 0.7 % en la población mestiza y una frecuencia variable de gUMs CYP2C19 (0.0 a 32.6 %, más prevalente en afrocaribeños) en las poblaciones costarricenses. Por último, los siguientes alelos fueron positivamente correlacionados con la ancestría africana y negativamente con la ancestría nativa americana: CYP2D6*5 (actividad nula), CYP2D6*17, CYP2D6*29 (ambos de actividad disminuida) y CYP2C19*17 (actividad incrementada). No se encontró correlación entre los polimorfismos CYP2C9 y la ancestría. Se requieren estudios posteriores que evalúen la secuencia de CYP2C9 y CYP2C19 en estas poblaciones, preferiblemente mediante la secuenciación de estos genes.

Multiplex Phenotyping for Systems Medicine: A One-Point Optimized Practical Sampling Strategy for Simultaneous Estimation of CYP1A2, CYP2C9, CYP2C19, and CYP2D6 Activities Using a Cocktail Approach.

Phenotyping of the CYP450 enzyme activities contributes to personalized medicine, but the past phenotyping approaches have followed a piecemeal strategy measuring single enzyme activities in vivo. A barrier to phenotyping of populations in rural and remote areas is the limited time and resources for sample collection. The CEIBA cocktail approach allows metabolic capacity estimation of multiple CYP450 enzymes in a single sample analysis, but the attendant sample collection schemes for applications in diverse global settings are yet to be optimized. The present study aimed to select an optimal matrix to simultaneously analyze CYP450 enzyme activities so as to simplify the sampling schemes in the phenotyping protocol to enhance its throughput and feasibility in native populations or in remote and underserviced geographies and social contexts. We evaluated 13 Ecuadorian healthy volunteers for CYP1A2, CYP2C9, CYP2C19, and CYP2D6 genotypes and their metabolic phenotypes, including CYP3A4, in plasma and urine after administering one reduced dose of caffeine, losartan, omeprazole, and dextromethorphan. Pharmacokinetic analyses were performed, and the correlation between AUC parent/AUC metabolite and the ratio between concentrations of probe drugs and their corresponding metabolites at timepoints ranging from 0 to 12 hours post-dose were analyzed. A single sampling timepoint, 4 hours post-dose in plasma, was identified as optimal to reflect the metabolic activity of the attendant CYP450 enzymes. This study optimizes the CEIBA multiplexed phenotyping approach and offers new ways forward for integrated drug metabolism analyses, in the pursuit of global personalized medicine applications in resource-limited regions, be they in developed or developing countries.

Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population.

CYP2C9, CYP2C19 and CYP2D6 metabolize around 40% of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry. A total of 448 healthy individuals were included in the study: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limón. CYP2C9 (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined by Real-Time PCR. African, European and Native American ancestry were inferred using 87 ancestry informative markers. The frequency of the decreased activity allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the admixed population, and the highest frequencies of CYP2C19*2 (null activity) and the CYP2C19*17 (increased activity) were found in the self-reported Afro-Caribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following alleles were positively correlated with genomic African ancestry and negatively correlated with genomic Native American ancestry: CYP2D6*5 (null activity), CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17 (increased activity). No correlation for CYP2C9 polymorphisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted.

Worldwide interethnic variability and geographical distribution of CYP2C9 genotypes and phenotypes.

INTRODUCTION: Notably differences in CYP2C9 allele frequencies among worldwide populations have been reported, with an interesting low frequency of the CYP2C9*2 allele in Amerindians compared with Admixed and European populations. AREAS COVERED: Literature was searched using the PubMed database and was focused on worldwide original research papers on CYP2C9 alleles and CYP2C9 phenotypes ("predicted" from CYP2C9 genotypes and "measured" metabolic phenotype with a probe drug) among healthy volunteers according to their ethnicity and geographical distribution. Seventy-eight original research articles including a total of 31,978 subjects were identified. EXPERT OPINION: CYP2C9*2 allele is the most frequent in Caucasian populations (average 14%), with the lowest frequencies for Africans (0.46%), East Asians (0.56%) and Native Americans (1.25%), which is in agreement with the hypothesis about the low prevalence in Amerindians. CYP2C9*3 shows the highest frequency among South Asians (11.7%), while CYP2C9*5 (1.56%) and *8 (4.70%) in African Americans. The predicted poor metabolizers (gPMs) were found overall in a low frequency, with the highest frequency detected for South Asians, in accordance with the CYP2C9*3 frequency in these populations. This study shows the worldwide variability in the CYP2C9 allele frequencies across different ethnic and geographic groups. Data about CYP2C9 "measured" metabolic phenotypes is still limited.

Pharmacogenetics in Central American healthy volunteers: interethnic variability.

Ethnicity is one of the major factors involved in interindividual variability to drug response. This study aims to describe the frequency of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in Central American healthy volunteers and to determine its interethnic variability. Twenty-six original research articles on allelic, genotypes or metabolic phenotype frequencies were analyzed, in which a total number of 7611 Central American healthy volunteers were included (6118 were analyzed for genotype and 1799 for metabolic phenotype). No reports were available for population from Belize and Honduras. The CYP2D6*4 and *5 frequencies in Amerindian populations from Costa Rica have shown to be among the highest frequencies so far reported in the world. Furthermore, NAT2*5 and *6 presented higher frequencies in admixed populations than in Amerindians, but, inversely, the NAT2*7 was more frequent in Amerindians compared to an admixed population. Likewise, different patterns of distribution have been shown in HLA-A*02, *03 and HLA-B*07 among Native populations from Latin America. Reports on Central American populations were also found for the CYP2C19, LDLR, CYP2E1, MDR1, G6PD, TP53, CYP1A2, CYP3A4 and CYP3A5 biomarkers, but no data were available for the other 91 pharmacogenetic biomarkers revised in Central American populations. Differences in the frequency of some pharmacogenetic biomarkers and metabolic phenotypes were found, showing interethnic variability within Central American and with other Latin American populations.

Interethnic variability of CYP2D6 alleles and of predicted and measured metabolic phenotypes across world populations.

INTRODUCTION: The frequency of CYP2D6 alleles, related to either a lack of or increased enzymatic activity, which may lead to poor metabolism (PM) or ultrarapid metabolism (UM), can vary across ethnic groups and hence across geographic regions. AREAS COVERED: Worldwide original research papers on CYP2D6 allelic frequencies, metabolic phenotype frequencies measured with a probe drug, and/or genotype frequencies that studied > 50 healthy volunteers, were included in analyses to describe the distributions of alleles, phenotypes predicted from genotypes (predicted poor metabolizers [gPMs], predicted ultrarapid metabolizers [gUMs]) and metabolic phenotypes (mPMs, mUMs) across ethnic groups and geographic regions. The analysis included 44,572 individuals studied in 172 original research papers. EXPERT OPINION: As of today, Africa and Asia are under-represented in this area relative to the total number of their inhabitants, so that further studies in these regions are warranted. The CYP2D6*4 allele frequency was higher in Caucasians, CYP2D6*10 in East Asians, CYP2D6*41 and duplication/multiplication of active alleles in Middle Easterns, CYP2D6*17 in Black Africans and CYP2D6*29 in African Americans, than in other ethnic groups. Overall, gPMs and mPMs are more frequent among Caucasians, and gUMs among Middle Easterns and Ethiopians. However, mUMs could not be evaluated because only two studies were found presenting this information. Further studies including mUMs are thus warranted. There is a correspondence between gPMs and mPMs, but the few studies of mUMs meant that their relationship with gUMs could not be demonstrated. Finally, evolutionary aspects of the CYP2D6 allele distribution appear to support the Great Human Expansion model.

MDR-1 genotypes and quetiapine pharmacokinetics in healthy volunteers.

BACKGROUND: P-glycoprotein is an efflux transporter encoded by the multidrug-resistance MDR-1 gene, which influences the absorption and excretion of a variety of drugs. The relation between quetiapine pharmacokinetics and MDR-1 genetic polymorphisms remains controversial. Therefore, the aim of the present study was to analyze the association between quetiapine plasma concentrations and MDR-1 genetic polymorphisms in a bioequivalence trial. METHODS: Quetiapine bioequivalence was studied in 24 unrelated healthy Caucasian adults with an open-label, randomized, cross-over, two-sequence and two-period design. Subjects were genotyped for 3435C>T and 1236C>T single-nucleotide polymorphisms. A linear mixed model was performed to compare pharmacokinetic parameters. RESULTS: Subjects with 3435T/T genotype vs. C carriers showed a higher area under the concentration-time curve from 0 to 36 h (p=0.01). Subjects classified according to 1236C>T SNP and haplotypes showed no statistically significant differences. CONCLUSIONS: These results suggest that the polymorphic MDR-1, in particular the 3435C>T allelic variant, might influence plasma levels of quetiapine.

Pharmacogenetics of clinical response to risperidone.

Despite risperidone's proven safety and efficacy, existing pharmacogenetic knowledge could be applied to improve its clinical use. The present work aims to summarize the information about genetic polymorphisms affecting risperidone adverse reactions and efficacy during routine clinical practice. The most relevant genes involved in the metabolism of the drug (i.e., CYP2D6, CYP3A and ABCB1) appear to have the greatest potential to predict differences in plasma concentrations of the drug and its interactions, but also relate to side effects, such as neuroleptic syndrome, weight gain or polydipsia. Other genes that have been found in association at least twice with any adverse reactions including metabolic changes, extrapyramidal symptoms or prolactine increase are: 5HT2A; 5HT2C; 5HT6; DRD2; DRD3; and BDNF. Some of these genes (5HTR2A, DRD2 and DRD3), along with 5-HTTLPR and COMT, have also been reported to be related with negative clinical outcomes. However, there is not yet enough evidence to support their routine screening during clinical practice.

Marcadores autoinmunes en el lupus eritematoso sistémico / Autoinmune markers in Systemic Lupus Erythemathosus

En este trabajo se determinó el valor clínico de varios marcadores en el lupus eritematoso sistémico (LES). Muestras de suero de 33 pacientes fueron estudiadas para la presencia de anticuerpos antinucleares (inmunofluorescencia indirecta, ANA-IFI) y de las especificidades siguientes: anti-DNA de doble cadena (radioinmunoensayo, anti-Sm/RNP, anti-Ro, anti-Scl-70 y anti-Jo-1 (ensayo inmunoenzimático). También se evaluó la presencia del factor reumatoide (FR, aglutinación de latex) y de los inmunocomplejos circulantes; estos últimos, determinados por los métodos de precipitación con polietilenglicol (ICC-PEG) y el inmunoenzimático basado en el reconocimiento del Ciq (ICC-Ciq). Resultados. Todos los pacientes fueron identificados por ANA-IFI y el 82 por ciento fueron positivos para los antiDNA. Los anti-Sm/RNP se encontraron en el 46 por ciento, los anti-Ro en el 30 por ciento, los anti-Scl-70 en el 15 por ciento, los anti-Jo-1 en el 3 por ciento y el FR en el 6 por ciento de los pacientes. La presencia de los ICC-PEG caracterizó el 39 por ciento y los ICC-Clq al 15 por ciento de los casos. Ninguno de los marcadores inmunológicos se asoció a la actividad de la enfermedad ni al daño renal. Conclusiones. No obstante haber encontrado múltiples marcadores serológicos autoinmunes en el LES, no ha resultado evidente que éstos sean indicadores de la afección tisular de esta enfermedad

Determinación de los anticuerpos anti-DNA de doble cadena por los métodos de inmunofluorescencia indirecta y por radioinmunoanálisis de fase líquida / Deterination of double chain anti-DNA antibodies by indirect immunofluorescence and liquid phase radioimmunoassay

Con el objetivo de validar las láminas de Crithidia luciliae (CL) de producción nacional (Centro Nacional de Biopreparados, Cuba) se estudió la presencia de los anticuerpos anti-DNA de doble cadena (anti-DNAdc) en las muestras séricas de 408 pacientes con enfermedades reumáticas, por los métodos de inmunofluorescencia indirecta con el empleo de CL (IFI-CL) y el radioinmunoanálisis (RIA) de fase líquida, U.K. Se observó una concordancia en el 85,05 % de los resultados obtenidos por ambos métodos, lo que se corresponde con un coeficiente Kappa de 0,662 (p<0,0001). La concordancia entre IFI-CL y el RIA resultó más alta (Kappa igual a 0,776, p<0,0001) cuando se consideraron los valores de anti-DNAdc menores de 20 U/mL y mayores de 50 U/mL obtenidos por RIA. La sensibilidad del método de IFI-CL para el diagnóstico del lupus eritematoso sistémico (LES) alcanzó el 61,17 %, y la especificidad el 73,39 %, mientras que la sensibilidad diagnóstica del RIA en relación con las cifras de anti-DNAdc superiores a 25 U/mL, rsultó del 60,19 % y la especificidad del 81,65

Determinación de los anticuerpos anti-DNA de doble cadena por los métodos de inmunofluorescencia indirecta y por radioinmunoanálisis de fase líquida / Determination of double chain anti-DNA antibodies by indirect immunofluorescence and liquid phase radioimmunoassay

Con el objetivo de validar las láminas de Crithidia luciliae (CL) de producción nacional (Centro Nacional de Biopreparados, Cuba) se estudió la presencia de los anticuerpos anti-DNA de doble cadena (anti-DNAdc) en las muestras séricas de 408 pacientes con enfermedades reumáticas, por los métodos de inmunofluorescencia indirecta con el empleo de CL (IFI-CL) y el radioinmunoanálisis (RIA) de fase líquida, U.K. Se observó una concordancia en el 85,05 % de los resultados obtenidos por ambos métodos, lo que se corresponde con un coeficiente Kappa de 0,662 (p<0,0001). La concordancia entre IFI-CL y el RIA resultó más alta (Kappa igual a 0,776, p<0,0001) cuando se consideraron los valores de anti-DNAdc menores de 20 U/mL y mayores de 50 U/mL obtenidos por RIA. La sensibilidad del método de IFI-CL para el diagnóstico del lupus eritematoso sistémico (LES) alcanzó el 61,17 %, y la especificidad el 73,39 %, mientras que la sensibilidad diagnóstica del RIA en relación con las cifras de anti-DNAdc superiores a 25 U/mL, rsultó del 60,19 % y la especificidad del 81,65

Monitoreo inmunológico con anticuerpos monoclonales de pacientes trasplantados de corazón: estudio preliminar / Imunologic monitoring with monoclonal antibodies of heart transplanted patients: preliminary study

Se estudiaron de forma seriada las poblaciones linfocitarias en sangre periférica reactiva con los anticuerpos monoclonales Behring Monoclonal Antibodies (BMA)-030 (pan-T), BMA-040 (T4) y BMA-081 (T8) en 15 pacientes trasplantados de corazón en nuestro centro. Se observaron diferencias significativas con tendencia al descenso de los valores relativos de los linfocitos T3 y T8 asociados a episodios de rechazo histológico y clínico del órgano aloinjertado. El cociente T4/T8 se comportó de forma dispersa e independiente del estado clínico. Se encontraron valores bajos de ciclosporina en sangre (* 250 ng/mL) en el 33,3

de determinaciones correspondientes a rechazo y en el 13,3

de las de funcionamiento estable del corazón. Se encontró una ligera tendencia al movimiento inverso entre los niveles de ciclosporina en sangre y los valores relativos de linfocitos T3 (p < 0,05), T4 (p < 0,01) y el cociente T4/T8 (p < 0,01). Se señala la importancia del estudo de una muestra numéricamente mayor que permita la valoración definitiva de la aplicación del monitoreo inmunológico inespecífico en el tratamiento clínico del paciente trasplantado de corazón

Monitoreo inmunológico con anticuerpos monoclonales de pacientes trasplantados de corazón: estudio preliminar / Immunologic monitoring with monoclonal antibodies of heart transplanted patients: preliminary study

Se estudiaron de forma seriada las poblaciones linfocitarias en sangre periférica reactiva con los anticuerpos monoclonales Behring Monoclonal Antibodies (BMA)-030 (pan-T), BMA-040 (T4) y BMA-081 (T8) en 15 pacientes trasplantados de corazón en nuestro centro. Se observaron diferencias significativas con tendencia al descenso de los valores relativos de los linfocitos T3 y T8 asociados a episodios de rechazo histológico y clínico del órgano aloinjertado. El cociente T4/T8 se comportó de forma dispersa e independiente del estado clínico. Se encontraron valores bajos de ciclosporina en sangre (* 250 ng/mL) en el 33,3 % de determinaciones correspondientes a rechazo y en el 13,3 % de las de funcionamiento estable del corazón. Se encontró una ligera tendencia al movimiento inverso entre los niveles de ciclosporina en sangre y los valores relativos de linfocitos T3 (p < 0,05), T4 (p < 0,01) y el cociente T4/T8 (p < 0,01). Se señala la importancia del estudo de una muestra numéricamente mayor que permita la valoración definitiva de la aplicación del monitoreo inmunológico inespecífico en el tratamiento clínico del paciente trasplantado de corazón