HLA in Jaidukama: an Amerindian secluded Colombian population with new haplotypes and Asian and Pacific-shared alleles.

America first inhabitants and peopling are still debated. In order to increase knowledge about these questions, we have aimed to detect HLA genes of an Amerindian secluded community: Jaidukama, who lives in North Colombia Equatorial forest. HLA genotyping and extended haplotype calculations were carried out in 39 healthy individuals belonging to 13 families. HLA frequencies were compared to other Amerindians and worldwide populations by calculating genetic distances, relatedness dendrograms and correspondence analyses. Only four DRB1 alleles were found (*0404, *0407, *1402 and *1602); however a total of 17 Amerindian different extended class I-class II HLA haplotypes were directly counted from the family studies, nine of them were specific of Jaidukamas. Some of the alleles or group of alleles within an extended haplotype (i.e. DQB1-DRB1) were also found in Asians and Pacific Islanders, further supporting existence of Asian and Pacific gene flow with Amerindians or a common founder effect. It is further supported that HLA extended haplotypes vary faster than alleles in populations. It is concluded that this unique model of Amerindian secluded families study suggests that rapid HLA haplotype variation may be more important than allele variation for survival (starting immune responses). This work may also be useful for future transplant programs in the area.

The Origin of Amerindians and the Peopling of the Americas According to HLA Genes: Admixture with Asian and Pacific People.

The classical three-waves theory of American peopling through Beringia was based on a mixed anthropological and linguistic methodology. The use of mtDNA, Y chromosome and other DNA markers offers different results according to the different markers and methodologies chosen by different authors. At present, the peopling of Americas remains uncertain, regarding: time of population, number of peopling waves and place of peopling entrance among other related issues. In the present review, we have gathered most available HLA data already obtained about First Native American populations, which raise some doubts about the classical three waves of American peopling hypothesis. In summary, our conclusions are: 1) North West Canadian Athabaskans have had gene flow with: a) close neighboring populations, b) Amerindians, c) Pacific Islanders including East Australians and d) Siberians; 2) Beringia was probably not the only entrance of people to America: Pacific Ocean boat trips may have contributed to the HLA genetic American profile (or the opposite could also be true); 3) Amerindians entrance to America may have been different to that of Athabaskans and Eskimos and Amerindians may have been in their lands long before Athabaskans and Eskimos because they present and altogether different set of HLA-DRB1 allele frequencies; 4) Amerindians show very few "particular alleles", almost all are shared with other Amerindians, Athabaskans and Pacific Islanders, including East Australians and Siberians; 5) Our results do not support the three waves model of American peopling, but another model where the people entrance is not only Beringia, but also Pacific Coast. Reverse migration (America to Asia) is not discarded and different movements of people in either direction in different times are supported by the Athabaskan population admixture with Asian-Pacific population and with Amerindians, 6) HLA variability is more common than allele veriability in Amerindians. Finally, it is shown that gene genealogy analises should be completed with allele frequency analyses in population relatednes and migrations studies.

HLA genes in Uros from Titikaka Lake, Peru: origin and relationship with other Amerindians and worldwide populations.

Uros population from the Titikaka Lake live in about 42 floating reed ('totora') islands in front of Puno City (Peru) at a 4000 m high altiplano. They present both an mtDNA and a human leucocyte antigen (HLA) profile different from the surrounding populations: mtDNA A2 haplogroup is common to Uros and Amazon forest lowland Amerindians. HLA genetic distances between populations have been calculated and neighbour-joining dendrograms and correspondence analyses were carried out. Approximately 15 006 HLA chromosomes from worldwide populations have been used for comparisons. Only eight HLA-A alleles have been found, three of them accounting for most of the frequencies. The same phenomenon is seen for HLA-B, HLA-DRB1 and HLA-DQB1 alleles: a few alleles (3, 4 and 3, respectively) are present in most individuals. The presence of HLA-B*4801 and HLA-DRB1*0901 alleles in a relatively high frequency (although not the most frequent alleles found) is a characteristic shared with Asians and some populations from the Andean altiplano. Three specific Uros haplotypes have been found among the most frequent ones: HLA-A*680102-B*3505-DRB1*0403-DQB1*0302; HLA-A*2402-B*1504-DRB1*1402-DQB1*0301; and HLA-A*2402-B*4801-DRB1*0403-DQB1*0302. The present study suggests that Uros may have been one of the first populations from the shores of the Titikaka Lake coming from the Amazonian forest, which might have given rise to other later differentiated ethnic group (i.e. Aymaras). Uros HLA profile is also useful to study genetic epidemiology of diseases linked to HLA and to construct a future transplant waiting list by adding up regional lists in order to get a bigger pool for transplanting with better HLA matching.

[Proliferative response of peripheral blood mononuclear cells to the recombinant allergen BtM of the Blomia tropicalis housedust mite]. / Respuesta proliferativa de células mononucleares de sangre periférica frente al alergeno recombinante BtM del ácaro del polvo casero Blomia tropicalis.

Allergic diseases are triggered when individuals genetically predisposed to developing an allergy (atopy) are exposed to sensitizing allergens. These allergens are captured and processed by antigen-presenting cells (APC) which presents them to T lymphocytes. Some of these allergens have a significant influence on the development of this type of disease and cause most of the symptoms in allergic individuals around the world. They are found in the feces of house dust mites, which have diverse and varied origin in several species, for example the Blomia tropicalis (Bt) mite. In Cartagena (Colombia), this highly prevalent mite has been a central object of study by the Institute of Immunological Research of the University of Cartagena, where several of its allergens have been cloned, sequenced and expressed as recombinant allergens. Moreover, their capacity to bind to IgE and the frequency of this process has been studied. The aim of the present study was to analyze the lymphoproliferative response of peripheral blood mononuclear cells (PBMC) in healthy and allergic individuals to one of the recombinant allergens of B. tropicalis, BtM. This response was studied in PBMC from six patients with allergy to Bt (positive cutaneous test to Bt extract), using a cellular proliferation technique, with incorporation of 3H thymidine at days 3 and 6 days of culture, and at three different concentrations of BtM. Notable among the results was the high proliferation produced by cells from patient JF018 at 3 days of stimulus (41.7 IE), with the lowest concentration of protein (100 microg/mL). Moreover, in all the experiments this concentration was the cause of most of the cell proliferation. In addition, some response to control LAC012 against glutathione-S-transferase (GST) was induced. In conclusion, the results of the present study demonstrate that the recombinant allergen BtM is able to induce a cellular response in the PBMC of patients allergic to Bt. Moreover, it is able to induce a response similar to that produced by natural allergens, because its pattern of response is similar to that shown by cells stimulated with Bt extract. These results also show that a process of anergy can be produced in cells when excess antigen is present. In some individuals (both allergic and nonallergic), GST is able to cause a proliferative response, indicating its sensitizing potential in these individuals.

Respuesta proliferativa de células mononucleares de sangre periférica frente al alergeno recombinante BtM del ácaro del polvo casero Blomia tropicalis / Proliferative response of peripheral blood mononuclear cells to the recombinant allergen BtM of the Blomia tropicalis mite

Las enfermedades alérgicas se desencadenan cuando los individuos que tienen predisposición genética a desarrollar algún tipo de alergia (atópicos), se exponen a alergenos sensibilizantes. Estos alergenos son captados y procesados por las células presentadoras de antígenos (CPA), que de igual forma los presentan a los linfocitos T. Algunos de estos alergenos tienen una mayor incidencia en el desarrollo de este tipo de patologías y son causantes de las mayores molestias en individuos alérgicos alrededor del mundo, son ellos los encontrados en las heces de los ácaros del polvo casero, los cuales tienen un origen diverso y variado en varias especies, como por ejemplo el ácaro Blomia tropicalis. En Cartagena de Indias, este ácaro de alta prevalencia, ha sido objeto central de estudio por el instituto de investigaciones inmunológicas de la Universidad de Cartagena, en donde se han logrado clonar, secuenciar y expresar varios de sus alergenos como proteínas recombinantes, además se les ha estudiado su capacidad y frecuencia de unión a la IgE. El presente estudio se realizó con el objetivo de analizar la respuesta linfoproliferativa de las células mononucleares de sangre periférica (CMSP) de individuos alérgicos y sanos, a uno de los alergenos recombinantes de Blomia tropicalis, el BtM. Dicha respuesta se estudió en CMSP de 6 pacientes alérgicos a Bt (con prueba cutánea positiva al extracto de la misma), utilizando una la técnica de proliferación celular, con incorporación de timidina tritiada, a 3 y 6 días de cultivo y a tres diferentes concentraciones de BtM. De los resultados obtenidos se destaca, la alta proliferación causada por las células del paciente JF018 a los 3 días de estímulo (41,7 IE), con la concentración más baja de proteína (100 g/mL), además, sobresale el hecho que esta concentración fue la causante de la mayor proliferación, de las células, en todos los experimentos. También, se indujo alguna respuesta del control LAC012, contra la glutation-S-transferasa (GST). En conclusión, los resultados del presente estudio demostraron que el alergeno recombinante BtM, es capaz de inducir una respuesta celular en CMSP de pacientes alérgicos a Bt, además, tiene la capacidad de inducir una respuesta similar a la producida por los alergenos naturales, pues su patrón de respuesta se asemeja al mostrado por las células estimuladas con el extracto del ácaro. Además estos resultados muestran, que se puede estar desarrollando un proceso de anergia en las células cuando estas se encuentran en presencia de exceso de antígeno. También es de resaltar que en algunos individuos (tanto alérgicos como sanos), la GST es capaz de causar respuesta proliferativa indicando su potencial poder sensibilizante en estos individuos (AU)

Allergic diseases are triggered when individuals genetically predisposed to developing an allergy (atopy) are exposed to sensitizing allergens. These allergens are captured and processed by antigen-presenting cells (APC) which presents them to T lymphocytes. Some of these allergens have a significant influence on the development of this type of disease and cause most of the symptoms in allergic individuals around the world. They are found in the feces of house dust mites, which have diverse and varied origin in several species, for example the Blomia tropicalis (Bt) mite. In Cartagena (Colombia), this highly prevalent mite has been a central object of study by the Institute of Immunological Research of the University of Cartagena, where several of its allergens have been cloned, sequenced and expressed as recombinant allergens. Moreover, their capacity to bind to IgE and the frequency of this process has been studied. The aim of the present study was to analyze the lymphoproliferative response of peripheral blood mononuclear cells (PBMC) in healthy and allergic individuals to one of the recombinant allergens of B. tropicalis, BtM. This response was studied in PBMC from six patients with allergy to Bt (positive cutaneous test to Bt extract), using a cellular proliferation technique, with incorporation of 3H timidine at days 3 and 6 days of culture, and at three different concentrations of BtM. Notable among the results was the high proliferation produced by cells from patient JF018 at 3 days of stimulus (41.7 IE), with the lowest concentration of protein (100μg/mL). Moreover, in all the experiments this concentration was the cause of most of the cell proliferation. In addition, some response to control LAC012 against glutathione-S-transferase (GST) was induced. In conclusion, the results of the present study demonstrate that the recombinant allergen BtM is able to induce a cellular response in the PBMC of patients allergic to Bt. Moreover, it is able to induce a response similar to that produced by natural allergens, because its pattern of response is similar to that shown by cells stimulated with Bt extract. These results also show that a process of anergy can be produced in cells when excess antigen is present. In some individuals (both allergic and nonallergic), GST is able to cause a proliferative response, indicating its sensitizing potential in these individuals (AU)

Hydrocarbon contamination in Cartagena Bay, Colombia.

This study deals with the levels of aromatic and aliphatic hydrocarbon quantification in sediments and organisms in Cartagena Bay (Colombia), 1996-1997. Sediments (14 stations) and bivalves (2 stations) were monitored at different times of the year. Areas with high values were in the north with concentrations above 100 microg/g with a maximum of 1415 microg/g. Areas with low values were located toward the south, near the outlet of the Canal del Dique and Barú Island, with values below 10 microg/g. In other areas concentrations were between 50 and 100 microg/g. A decrease in sediment concentrations of hydrocarbons has occurred since 1983, but levels in some sectors are still similar to those in polluted areas. Organisms have relatively low values (8-30 microg/g for bivalves, and 10-40 microg/g for fish).