Banco de donantes voluntarios de células progenitoras hematopoyéticas. Proyecto Panama Dono

Introducción; El Trasplante de Células Progenitoras Hematopoyéticas es actualmente un tratamiento para diferentes desordenes hematológicos malignos y no malignos, que se efectúa cuando existe un receptor con un donante idéntico o haploidéntico para los genes del Complejo Mayor de Histocompatibilidad. En ausencia de donante familiar compatible, hemos creado el Programa de Donantes Voluntarios con tipificación del Sistema HLA. que han expresado su consentimiento de ser donantes y comparten los alelos del Sistema de linfocitos humanos codificados en el brazo corto del cromosoma seis. Materiales y métodos: El presente estudio es un estudio descriptivo, observacional y transversal que presenta los resultados de la búsqueda de donantes voluntarios para receptores sin donante familiar en el Programa Panamá Dono y su aplicación en Panamá. Resultado: De los grupos familiares estudiados que incluye receptor y donantes familiares, un total de 783 personas estudiadas aceptaron voluntariamente ser donantes no relacionados y sus tipificaciones HLA incorporadas al Programa Panamá Dono. Un total de 321 pacientes sin donante idéntico o haploidentico en su grupo familiar, se les ha buscado donante no relacionado en el Programa y se logró Trasplantar el primer receptor con un donante voluntario compatible en 16 genes del Complejo Mayor de Histocompatibilidad en el Hospital del Niño. Conclusión: El Laboratorio Nacional de Trasplante de la Caja de Seguro Social ha logrado crear el Programa de Donantes Voluntarios de Células Progenitoras Hematopoyéticas denominado PANAMA DONO, que consta de 788 panameños que han expresado su consentimiento. En la actualidad una paciente del Hospital del Niño fue trasplantada en 2022 con esta modalidad de donante compatible no relacionado. La compatibilidad idéntica de la receptora con el donante voluntario fue de 16 alelos idénticos del Complejo Mayor de Histocompatibilidad. (provisto por Infomedic International)

Introduction: Hematopoietic Progenitor Cell Transplantation is currently a treatment for different malignant and non-malignant hematological disorders, which is performed when there is a recipient with an identical or haploidentical donor for the genes of the Major Histocompatibility Complex. In the absence of a compatible family donor, we have created the Volunteer Donor Program with HLA System typing, who have expressed their consent to be donors and share the alleles of the human lymphocyte system encoded on the short arm of chromosome six. Materials and methods: The present study is a descriptive, observational, and cross-sectional study that presents the results of the search for volunteer donors for recipients without a family donor in the Panama Dono Program and its application in Panama. Results: Of the family groups studied, which included recipients and family donors, a total of 783 persons studied voluntarily accepted to be unrelated donors and their HLA typing incorporated into the Panama Dono Program. A total of 321 patients without an identical or haploidentical donor in their family group have been searched for unrelated donors in the Program and the first recipient was transplanted with a voluntary donor compatible in 16 genes of the Major Histocompatibility Complex in the Hospital del Niño. Conclusion: The National Transplant Laboratory of the Social Security Fund has managed to create the Program of Voluntary Donors of Hematopoietic Progenitor Cells called PANAMA DONO, which consists of 788 Panamanians who have expressed their consent. Currently a patient from the Hospital del Niño was transplanted in 2022 with this unrelated compatible donor modality. The identical compatibility of the recipient with the volunteer donor was 16 identical alleles of the Major Histocompatibility Complex. (provided by Infomedic International)

Algoritmo De Selección De Receptores Altamente Sensibilizados En Lista De Espera Modalidad Donante Fallecido En Panamá. 2021

El Sistema de antígenos de Leucocitos Humanos (HLA) juega un papel funcional en la presentación de péptidos al sistema Inmune. El grado de compatibilidad de los antígenos de los leucocitos humanos (HLA) de los loci -A, -B, -DRB1 entre el receptor en lista de espera y el donante, y la ausencia de anticuerpos específicos contra los antígenos HLA del donante, tienen la mejor sobrevida en un trasplante. El nuevo algoritmo de selección de receptores sensibilizados en lista de espera, que se introduce en el presente trabajo, tiene como objetivo mejorar su posibilidad de recibir riñones provenientes de un donante fallecido. Este algoritmo cumple etapas que se siguen en la selección del receptor sensibilizado compatible con el donante fallecido. Previo a incorporar un paciente en la lista de espera, es requisito conocer el grado de sensibilización a los antígenos del sistema de Leucocitos Humanos (HLA). El Laboratorio Nacional de Trasplante ha incorporado el Panel Reactivo de Anticuerpos Calculado (cPRA) que utiliza la frecuencia de antígenos HLA de la población panameña, en sustitución del Panel Reactivo de anticuerpos (PRA) que utiliza la frecuencia de alelos de otra población que no es la panameña. (provisto por Infomedic International)

The Human Leukocyte Antigen (HLA) system plays a functional role in the presentation of peptides to the immune system. The degree of compatibility of human leukocyte antigens (HLA) loci -A, -B, -DRB1 between the waiting list recipient and the donor, and the absence of specific antibodies against the donor HLA antigens, have the best survival in transplantation. The new algorithm for the selection of sensitized recipients on the waiting list, introduced in the present work, aims to improve their chance of receiving kidneys from a deceased donor. This algorithm fulfills stages that are followed in the selection of the sensitized recipient compatible with the deceased donor. Before adding a patient to the waiting list, it is a requirement to know the degree of sensitization to the antigens of the Human Leukocyte Antigen System (HLA). The National Transplant Laboratory has incorporated the Calculated Reactive Panel of Antibodies (cPRA) that uses the frequency of HLA antigens of the Panamanian population, replacing the Reactive Panel of Antibodies (PRA) that uses the frequency of alleles of another population that is not Panamanian. (provided by Infomedic International)

HLA allele and haplotype frequencies in the Panamanian population.

In this study, we report for the first time HLA allele and haplotype frequencies in the modern Panamanian population at a two-field (four digits) resolution level. Reported frequencies were calculated from genotype data for the HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 loci of 462 healthy unrelated Panamanian adults of Hispanic ethnicity. In addition to providing new insights on the allelic structure of the Panamanian population and its origin, these data are critical for better planning of healthcare strategies in the country and for future research exploring the association with certain chronic and infectious diseases.

HLA genetic profile of Mapuche (Araucanian) Amerindians from Chile.

Amerindian Mapuche (Araucanians) are now living in Chile and Argentina at both sides of Andean Mountains. They are anthropologically and genetically different from southernmost South America Patagonian Amerindians. Most of the HLA alleles found in our Mapuche sample are frequent or very frequent in North and South America Amerindians: (1) Class I: A*02:01, A*03:01, A*68:01, B*39:09, B*51:01, (2) Class II: DRB1*03:01, DRB1*04:03, DRB1*07:01, DRB1*08:02, DRB1*14:02, DRB1*16:02. One of the nine most frequent extended haplotypes seems to be from European origin, suggesting the existence of a degree of admixture with Europeans in our Mapuche sample. It has been calculated of about 11 % admixture. Three of the extended haplotypes are also found in other Amerindians and five of them are newly found in Mapuche Amerindians: A*68:01-B*39:09-DRB1*08:02-DQB1*04:02; A*68:01-B*51:01-DRB1*04:03-DQB1*03:02; A*29:01-B*08:01-DRB1*03:01-DQB1*02:01; A*02:01-B*15:01-DRB1*04:03-DQB1*03:02; A*33:01-B*14:02-DRB1*07:01-DQB1*03:03. The medical importance of calculating HLA profile is discussed on the diagnostic (HLA and disease) and therapeutical bases of HLA pharmacogenomics and on the construction of a virtual transplantation HLA list profile. Also, anthropological conclusions are drawn.

Young male survivor of a spontaneous left main coronary artery dissection treated with surgery.

Spontaneous dissection of the coronary arteries is a rare disease with a wide range of clinical presentations ranging from angina to myocardial infarction (MI); its pathophysiology has not yet been fully established. In this paper, we present the case of a 31-year-old male with an acute coronary syndrome. The initial results of the electrocardiogram and cardiac enzymes were consistent with MI. However, a coronary angio-tomography revealed a dissection of the left main coronary artery and the patient underwent emergent surgery with coronary artery bypass grafting. The treatment of spontaneous dissection of the coronary arteries depends on the anatomical location and the patient's clinical presentation. Coronary revascularization is associated with good results.

HLA genes in Amerindian immigrants to Madrid (Spain): epidemiology and a virtual transplantation waiting list: Amerindians in Madrid (Spain).

Amerindians immigrated to Madrid (Spain) region are about 10% of the present day population. Amerindians are believed to be the first American inhabitants, before Na-Dene speakers, Aleuts and Eskimo. They may initially have arrived to America from Siberia and also from other parts of Pacific Sea (South Asia, Polynesia and Australia). Nowadays, they populate America from Canada to Tierra del Fuego (South America tip South). Most Amerindian immigrants to Madrid have come from Andean Countries in the last 10 years (mainly Ecuador, Bolivia, Peru and Colombia). They show an HLA profile with "quasi-specific alleles", which makes them different to the rest of the World. In the present work, we have aimed to determine the immigrants HLA profile in order to establish a virtual transplantation waiting list which may be useful for their therapeutic transplants, particularly bone marrow transplantation. This would be carried out together with Amerindian immigrants to other parts of Spain and with their own countries in order to build up transplantation programs. Specific epidemiology programs on HLA linked disease will also be established. Immigrant volunteer unrelated blood donors contributed to the present study. HLA typing was performed by standard methods and their HLA profile obtained and obtained and compared with 15,108 HLA chromosomes from the rest of the World, including Spaniards. The immigrants showed a typical Amerindian profile similar to isolated Amerindian ethnic groups and altogether different to other World inhabitants (including Spaniards). These are the first bases to set up transplantation and epidemiology studies in collaboration with their original population in America. Finally, the HLA profile found in these Amerindians does not indicate their American specific original area, as it is expected from previous studies, i.e.: they do not relate more with Andean than with other Amerindians in Neighbour Joining dendrograms or correspondence analyses.

Trombosis aguda de la vena porta, reporte de un caso y revisión bibliográfica / Acute thrombosis of the portal vein, a case report and literature review

La pileflebitis es una tromboflebitis de la vena porta o de alguna de sus ramas tributarias, infrecuente complicación de procesos inflamatorios intra-abdominales que pueden llevar a la trombosis de la vena porta y a abscesos hepáticos. La trombosis de la vena porta puede ocurrir fuera del hígado (extrahepática) o dentro del hígado (intrahepática). Las causas de la trombosis portal extrahepática incluyen la oclusión por adenomegalias, inflamación de la vena porta debido a pileflebitis ascendente secundario a la infección del apéndice o colon, trombosis de la vena esplénica secundaria a pancreatitis o a procedimientos quirúrgicos abdominales. Las causas de la trombosis intrahepática son la cirrosis hepática, la invasión tumoral por tumores hepáticos primarios o secundarios. La pileflebitis es habitualmente una complicación de la apendicitis, pero la incidencia de esta enfermedad ha disminuido en forma importante debido a los avances en la terapia antibiótica y a las modernas técnicas quirúrgicas. El caso reportado a continuación se presenta asociado a un cuadro de enteritis aguda (pocos casos reportados) con hallazgo de niveles elevados de homocisteína como condición trombogénica de base previamente desconocida.

HLA class I and class II haplotypes in admixed families from several regions of Mexico.

We studied HLA class I and class II alleles in 191 Mexican families (381 non-related individuals) to directly obtain the HLA-A/B/DRB1/DQB1 haplotypes and their linkage disequilibrium (LD). The most frequent HLA haplotypes observed were: A*02-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*04-DQB1*0302, A*68-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*08-DQB1*04, A*33-B*1402-DRB1*01-DQB1*05, and A*24-B*35-DRB1*04-DQB1*0302. The four most common haplotypes found by our study involve those previously reported in Amerindian populations. LD analysis of HLA-A-B and HLA-B-DRB1 loci showed significant associations between A29(19)-B44(12), A33(19)-B65(14), A1-B8, A26(19)-B44(12), A24(9)-B61(40), B65(14)-DR1, B8-DR17(3), B44(12)-DR7, B7-DR15(2), and B39(16)-DR4. Also, all DRB1-DQB1 associations showed significant LD values. Admixture estimations using a trihybrid model showed that Mexicans from the State of Sinaloa (Northern Mexico) have a greater proportion of European genetic component compared with Mexicans from the Central area of Mexico, who have a greater percentage of Amerindian genes. Our results are important for future comparative genetic studies of different Mexican ethnic groups with special relevance to disease association and transplantation studies.

HLA genes of Aleutian Islanders living between Alaska (USA) and Kamchatka (Russia) suggest a possible southern Siberia origin.

Aleuts HLA profile has been compared with that of neighboring and worldwide populations. Thirteen thousand one hundred and sixty-four chromosomes have been used for this study. Computer programs have obtained HLA allele frequencies, genetic distances between populations, NJ relatedness dendrograms, correspondence analysis and most frequent HLA extended haplotypes. Aleuts have inhabited Aleutian Islands since about 9000 years BP according to fossil and genetic (mtDNA) records. They are genetically different to Eskimo, Amerindian and Na-Dene speakers according to their HLA profile; this correlates with cultural and anthropological Aleut distinctiveness. No typical Amerindian HLA alleles have been found in a significant frequency. Their HLA relatedness to Saami (or Lapps, northern Scandinavians), Finns and Pomors (North-West Russia) indicates an ancient possible origin from the Baikal Lake Area (southern Siberia) around the present day Buryat peopling area; other origins are not discarded. Aleuts characteristic HLA profile may influence future transplantation programs in the region and be useful to study diseases linked to HLA epidemiology.

Origin of Mexican Nahuas (Aztecs) according to HLA genes and their relationships with worldwide populations.

A Nahua Aztec isolated group from Morelos State (Mexico) was studied for their HLA profile. The relationship with other Amerindians and worldwide populations was studied by using 13,818 chromosomes and calculating Nei's chord genetic distances (DA), neighbor-joining dendrograms and correspondence multidimensional values. Three new HLA extended haplotypes were found in our group: A*30-B*49-DRB1*1001-DQB1*0501 (the most frequent one in this population), A*02-B*52-DRB1*1402-DQB1*0301 and A*68-B*61-DRB1*1602-DQB1*0303. Both genetic distances and correspondence analyses clearly show that our Nahua isolated group is genetically close to some of the most ancient groups living in Mexico (Mayans, Zapotecans, Mixtecans). This suggests that Nahua language (Nahuatl) may have been imposed to scattered groups throughout Mexico; otherwise Aztecs may have been living in Mexico long before their postulated immigration in the XII century AD.

HLA genes in Cubans and the detection of Amerindian alleles.

Caribbean Islands including Cuba were first inhabited by Meso-American and later by Arawak-speaking Amerindians from nowadays Venezuela. Spanish invaders brought to almost extinction to the Amerindian population after 1492. Black slaves from West Africa were taken into Cuba by Europeans. The degree of admixture among populations is approached. HLA alleles were studied by DNA techniques. Comparison with other worldwide populations (a total of 14.094 chromosomes) included genetic distances, Neighbour-Joining dendrograms, correspondence analyses and calculation of extended haplotypes. While African-European HLA features were clearly found, Amerindian HLA characteristics are less evident, indicating that Amerindian devastation was particularly marked after 1492 AD. However, typical Amerindian alleles have been found in our Cuban sample, i.e. DRB1*0403, DRB1*0404, DRB1*0407, DRB1*0411, DRB1*0802 and DRB1*1602. The presence of Amerindian alleles in Cubans [corrected] may have a bear in the making up of transplantation registries (both for bone marrow and solid organ transplantation) at the regional level and also be important for epidemiological studies of diseases linked to HLA.

Origin of Bolivian Quechua Amerindians: their relationship with other American Indians and Asians according to HLA genes.

The Incas were Quechua-speaking people who settled down near Cuzco (Peru). They had an empire ranging from Ecuador to Chile, when Spanish conquerors seized their kingdom around 1532 AD. Nowadays, Quechua-speaking people inhabits Colombia, Ecuador, Bolivia, Peru and Argentina; however, Quechua language was imposed by both Incas and Spaniards to many non-Quechua speaking communities. We have taken a sample of Quechuan Bolivian blood donors from La Paz (Titicaca Lake region) where Inca-Quechuas themselves believed that came from. This group was compared with 6892 individuals from 68 different world populations regarding HLA/DNA allele frequencies distribution. Genetic distances, dendrograms and correspondence analyses were carried out in order to establish relationships among populations. The main conclusions are: (1) DRB1 and -DQB1 haplotypes shared with Asians are found in Quechuas and are not observed in other (Mesoamerican) Amerindians. (2) Aymara-speaking people from the same Titicaca Lake (La Paz) area shows close genetic distances with Quechuas in one dimension results (genetic distances); however, their HLA gene frequency distribution differs according to Neighbor-Joining (NJ) trees and correspondence analysis (multidimensional and more reliable analyses). Also, the common high frequency Asian and Athabascan HLA-DRB1*0901 allele is found in Quechuas in a significant frequency. Quechuas are clearly included within the Amerindian group.

HLA non-class II genes may confer type I diabetes susceptibility in a Mapuche (Amerindian) affected family.

A rare case of type I diabetes is studied in an Amerindian (Mapuche) family from Chile, analyzing glutamic acid decarboxylase, islet-cell autoantibodies and human leukocyte antigen (HLA) genes. The affected sib is the only one that has one specific HLA haplotype combination that differs from the other sibs only in the HLA class I genes. It is concluded that HLA diabetes susceptibility factors may be placed outside the class II region or even that susceptibility factors do not exist in the HLA region in this Amerindian family.

HLA genes in Mexican Teeneks: HLA genetic relationship with other worldwide populations.

The HLA allele frequency distribution of the Mexican Teenek Indians has been studied and compared with those of other First American Natives and worldwide populations (a total of 15694 chromosomes from 73 different populations were analyzed). This study corroborate the restricted HLA polymorphism in the Amerindian populations and demonstrate how the Amerindians show a relatively homogeneity as opposed to other First Native American groups. Finally, the present data support previous ones that state the lack of complete correlation between language and genetics in micro-environmental studies; Teenek Mayan language does not correspond with a close Mayan (Guatemala) relatedness.

HLA genes in Lamas Peruvian-Amazonian Amerindians.

The Lamas Amerindians are the Chancas descents who established before 1532 a.d. (Spanish conquest) at Lamas City, Wayku quarter in a Peruvian-Amazonian province (San Martin). The Lamas HLA profile shows significant differences with other Amerindians HLA profile, i.e.: (a) a higher number of newly found haplotypes compared to other studied Amerindian populations, particularly HLA-A*02-B*48-DRB1*0403-DQB1*0302, A*02-B*48-DRB1*0804-DQB1*0402 and A*02-B*40-DRB1*0407-DQB1*0302; (b) a relative high frequency of HLA-DRB1*0901 (a high frequency southern Asian allele) and HLA-B*48 (a Na-Dene, Siberian and Eskimo allele); both alleles are also found frequently in Quechuas and Aymaras, but not in many other (particularly Meso American) Amerindians and (c) correspondence and neighbor-joining dendrogram analyses show that Lamas (Chancas) may have an origin close to Amazonian Indians that later reached the Andean altiplano.

Human leukocyte antigen haplotypes and HFE mutations in Spanish hereditary hemochromatosis and sporadic porphyria cutanea tarda.

BACKGROUND AND AIMS: It has been postulated that the HFE C282Y mutation (linked to human leukocyte antigen [HLA]-A3-B7 haplotype) is not only responsible for hereditary hemochromatosis; HLA class I alleles would also contribute to the disease pathogenesis. In addition, H63D mutation linked to HLA-A29-B44 would also be pathogenetic, particularly in the Mediterranean Basin and throughout the world. However, sporadic porphyria cutanea tarda (s-PCT) has also been linked to these HFE mutations. In the present work, we have studied HFE mutations and HLA genes to test these hypotheses. METHODS: C282Y and H63D mutations together with HLA genetic typing have been performed in Spanish hereditary hemochromatosis (n = 98) and PCT (n = 63) patients. The etiologic fraction (delta) has been used to determine the absolute strongest gene linkage to both diseases. RESULTS: The Spanish frequent HLA-A29-B44 haplotype is not significantly associated to the H63D mutations in hereditary hemochromatosis patients (although it is found more frequently in patients than in controls). Sporadic porphyria cutanea tarda patients do not show a significant association to H63D mutations, although it is also more frequent than in controls; however, compound H63D/C282Y subjects seem to bear a significant risk to s-PCT. Allelic C282Y (and not H63D) frequencies show a significant association with s-PCT. CONCLUSIONS: The postulated additional risk of hereditary hemochromatosis given by class I HLA antigens may be secondary to the HFE gene linkage disequilibrium with certain class I alleles or to the existence of other neighboring genetic pathogenetic factors in our Spanish sample.

Different evolutionary pathway of B*570101 and B*5801 (B17 group) alleles based in intron sequences.

Two theories about MHC allele generation have been put forward: (1) point mutation diversification and/or (2) gene conversion events. A model supporting the existence of both of these mechanisms is shown in this paper; the possible evolution of the HLA-B*570101 and HLA-B*5801 alleles (which belong to the HLA-B17 serology group) is studied. The hypothesis favoured is that gene conversion events have originated these alleles, because intron sequences are also analysed. Evolution by point mutation should only be accepted if flanking introns have also been sequenced.

HLA genes in the Chuvashian population from European Russia: admixture of Central European and Mediterranean populations.

HLA alleles have been determined for the first time in individuals from the Chuvashian population by DNA typing and sequencing. HLA-A, -B, -DR, and -DQ allele frequencies and extended haplotypes have also been determined, and the results compared to those for Central Europeans, Siberians and other Asians, Caucasians, Middle Easterners, and Mediterranean peoples. Genetic distances, neighbor-joining dendrograms, and correspondence analysis have been performed. Present-day Chuvash speak an Altaic-Turkic language and are genetically related to Caucasians (Georgians), Mediterraneans, and Middle Easterners, and not only to Central or Northern Europeans; Chuvash contain little indications of Central Asian-Altaic gene flow. Thus, present-day Chuvash who speak an Altaic-Turkic language are probably more closely related to ancient Mesopotamian-Hittites and northern European populations than to central Asia-Altaic people.

[C0 vs C2 levels and their implications in kidney transplantation]. / CO vs C2 y sus implicaciones en trasplante renal.

We present a trial consisting of 52 kidney transplant patients with stable function, following a transplantation period of 3-6 months (group1), 6-12 months (group2) and more than 12 months (group3) and monitored by CO, C2 and Cyclosporine levels in blood. Mean serum creatinine level were in 1.1, 1.3 and 1.4 Mg/dl for group 1, 2 and 3 respectively. Mean Neoral doses (mg/kg/day) were 5.5, 4.4 and 3.0 for each group respectively. Mean CO (ng/ml) was 347.6 (group 1), 265.6 (group 2) and 207.6 (group 3), and mean C2 was 1353.5, 1098 and 904.2 for each group. 40% (2/5patients) from group2 and 41% (17/41patients) for group 3, had overexposure of the graft to Neoral; meantime 24% (10/41 patients) from group 3 shown C2 levels of underexposure. We conclude CO is a poor predictor of graft exposition to cyclosporine and C2 reflect more exactly this exposure.