Identification of HLA-B*14:41N in a NMDP Hispanic donor, selected for a patient of The Unrelated Mexican Donor Registry-DONORMO program in Mexico.

The B*14:41N allele was identified in a The National Marrow Donor Program (NMDP) Hispanic donor typed by our Mexican Registry-DONORMO.

Identification of A*29:47, previously typed as A*29:19, in a Mexican bone marrow donor from the state of Hidalgo, Mexico.

The A*29:47 allele was identified in a Mexican Mestizo unrelated bone marrow donor from the state of Hidalgo.

Identification of A*02:336 in a Mexican Mestizo acute lymphoblastic leukemia patient from the state of Veracruz.

A*02:336 was identified in a Mexican Mestizo ALL patient, born in the State of Veracruz.

Tratamiento del hiperparatiroidismo primario mediante abordaje mínimamente invasivo / Treatment of the primary hiperparatiroidism by minimally invasive boarding

The unilateral boarding of the primary hiperparatiroidism constitutes a technical option increasingly secondhand and adapted for the characteristics of this surgery. This type of boarding has been possible for the appearance of the Tc sestamibi, of the subspecialization of the surgery and of the determination of the PTH intraoperatory. Later we expose an epidemiological, descriptive and retrospective study from january 2004 to December 2008. During this time there were controlled in the hospital Ramon and Cajal of Madrid a total of 195 patients for primary hiperparatiroidism. Of them, 140 were submitted to unilateral exploration by suspicion of the solitary adenoma. The correlation between the findings of Tc sestamibi and surgical was correct in all the cases (139) except one concerns to right or left side. It failed in 30 cases in which there was detected badly the top and low location. As for the results the adenoma was extirpated correctly in 135 of 140 patients. This way we can say that the combination of the gammagraphy, a surgeon with experience and the support of the PTH intraoperatory they meet a high rate of treatment in case of adenomas in the unilateral boarding on a rate of hipercalcemia appellant or persistently between 3 percent-5 percent, rate similar to the obtained one for expert surgeons on having fulfilled an exploratory cervicotomy (considered "gold standard") but with minor postoperatory morbidity, minor pain and minor surgical time.

El abordaje unilateral del hiperparatiroidismo primario constituye una opción técnica cada vez más usada y apropiada debido a las características de esta cirugía. Este tipo de abordaje ha sido posible por la aparición del Tc sestamibi, de la subespecialización de la cirugía y de la determinación de la PTH intraoperatoria. A continuación exponemos un estudio epidemiológico, descriptivo y retrospectivo desde enero de 2004 a diciembre de 2008. Durante este tiempo fueron intervenidos en el hospital Ramón y Cajal de Madrid un total de 195 enfermos por hiperparatiroidismo primario. De ellos, 140 fueron sometidos a exploración unilateral por sospecha de adenoma único. La correlación entre los hallazgos gammagráficos y quirúrgicos fue correcta en todos los casos (139) menos uno en cuanto a lo que a lateralidad se refiere. Falló en 30 casos en los que se detectó mal la localización superior e inferior. En cuanto a los resultados, se extirpó el adenoma correctamente en 135 de los 140 pacientes. Así podemos decir que la combinación de la gammagrafía, de un cirujano con experiencia y el apoyo de la PTH intraoperatoria proporciona una elevada tasa de curación en el caso de adenomas paratiroideos en el abordaje unilateral con una tasa de hipercalcemia recurrente o persistente entre el 3 por ciento-5 por ciento, tasa similar a la obtenida por cirujanos expertos al realizar una cervicotomía exploradora (considerada gold standard) pero con menor morbilidad postoperatoria, menor dolor y menor tiempo quirúrgico.

Pseudoquiste de páncreas con extensión a mediastino / Pancreatic pseudocyst extended to the mediastinum: case report

We report a 53 years old male consulting for chest pain and dyspnea. On physical examination, an epigastric mass was detected. A TC scan showed a collection located in the omental bursa, which protruded over the posterior gastric wall and ascended to the mediastinum. Due to the presence of pancreatic calcifications, a pancreatic pseudocyst was suspected. The mediastinal cyst was drained percutaneously, leaving pig tail drainage in the cavity. Afterwards a cyst excision and Roux en Y gastrostomy was performed. After the surgical procedure the cyst became infected, requiring antimicrobials. After two weeks he was discharged in good conditions.

Los pseudoquistes de páncreas representan el 75 por ciento de las lesiones quísticas del páncreas y generalmente se circunscriben en el abdomen. Se presenta el caso de un paciente con un pseudoquiste de páncreas con extensión transhiatal a mediastino. Estos casos deben sospecharse mediante una historia clínica detallada y preguntando por antecedentes de dolor abdominal previo porque la clínica con la que se suelen manifestar es muy poco específica. El tratamiento de los pseudoquistes con extensión a mediastino debería ser el drenaje definitivo, bien de forma quirúrgica o endoscópica.

DRB1*1532, a new DR15 allele, identified in a Mexican unrelated donor from Veracruz, Mexico.

DRB1*1532 allele was identified in a Mexican unrelated marrow donor from the Gulf of Mexico.

Identification of B*9550, a novel B*15 allele, in a Mexican bone marrow donor from Veracruz State.

Human leukocyte antigen-B*9550 is a novel allele identified in a Mexican Mestizo bone marrow donor from Veracruz.

Distribution of the killer cell immunoglobulin-like receptors in Mexican Mestizos.

Understanding the complex interaction between human leukocyte antigen (HLA) and killer immunoglobulin-like receptor (KIR) requires study of both HLA and KIR diversity in the same population. The presence of KIR genes 2DL1, 2, 3, 4, 5, KIR3DL1, 3DL2, 3DL3, KIR2DS1, 2DS2, 2DS3, 2DS4, 2DS5, KIR3DS1, KIR3DP1, KIR2DP1 was determined in 54 unrelated Mexican Mestizo donors. The PCR sequence-specific oligonucleotide probe One Lambda kit (Luminex) kindly given by J. Lee was used for typing. The software analyses the combination obtained for each of the five exons. Five controls (UCLA DNA exchange) were run as quality control. The gene frequency (GF) was calculated for the 16 KIR loci; the GF of individual genes was 100% for 2DL4, 3DL1, 3DL2, 3DL3, 3DP1. KIR2DL1 (76.43%), KIR2DL2 (37.64%), KIR2DL3 (76.43%), KIR2DL5 (29.29%), KIR3DS1 (23.02%), KIR2DS1 (21.83%), KIR2DS2 (37.64%), KIR2DS3 (50.93%), KIR2DS4 (86.93%), KIR2DS5 (29.29%), KIR2DP1 (86.39%). We observed similar frequencies with Caucasians and Mediterraneans, with exceptions: KIR3DL1 which was present in 100% Mexicans, ranged from 62% to 75% in Caucasians; 2DS3 (50.9%) vs 14-20% 2DS4 (86.39%) vs 65-79% and 2DS5 (29.29%) vs 11-18% in Caucasians. The finding of 23 phenotypes in 54 individuals accounting for both chromosomes, demonstrates the enormous diversity. We found 14 different combinations of stimulatory KIRs in the phenotypes; every subject had at least one stimulatory KIR; in all of them, 2DS4 existed except for one person who may have some new combination: 2DS2 2DS3. Extended family data will offer accurate and precise haplotypes to provide an insight on the significance of ethnic distribution and KIR repertoire.

Mediterranean and Amerindian MHC class II alleles are associated with multiple sclerosis in Mexicans.

OBJECTIVES: Human leukocyte antigen (HLA)-DRB1, DQA1, DQB1 allele typing was performed in Mexicans Mestizos with multiple sclerosis (MS) to define the HLA class II alleles associated with the disease in this population. METHODS: Patients (n = 51) diagnosed according to the Poser criteria and a group of 173 unrelated healthy subjects were studied. PCR-SSOP and PCR-SSP were used for genotyping. RESULTS: Fifty five percent of the patients were females. The mean age at disease onset was 27 years. A relapsing-remitting disease was the most frequent type of MS (67%). A significant association of DRB1*0403 (OR = 5.68) with MS was shown. DRB1*0802 was also involved in susceptibility (OR = 2.41). An excess of DRB1*0802 homozygotes was observed in patients (P = 0.005), this genotype being in genetic equilibrium in controls. CONCLUSIONS: Two novel class II associations are described in Mexicans with MS: DRB1*0403 and DRB1*0802. Both alleles share with DRB1*1501, valine-86 and negatively charged amino acids, in the DRB1-anchoring motif of pocket 4.

Molecular analysis of HLA-DRB1, DQA1, DQB1, DQ promoter polymorphism and extended class I/class II haplotypes in the Seri Indians from Northwest Mexico.

The study of the genetics of the Major Histocompatibility Complex (MHC) in Amerindians is of great value in understanding the origins and migrations of these native groups, as well as the impact of immunogenetics on the epidemiology of diseases affecting these populations. We analyzed, using Polymerase Chain Reaction and Sequence Specific Oligonucleotide Probes (PCR-SSOP), DRB1, DQA1, DQB1 alleles and the promoter regions of DQA1 and DQB1 genes in 31 unrelated and 24 related Seri, a Mexican Indian group, from the state of Sonora (Northwest Mexico). The class II genotypes of this population were found to be in genetic equilibrium. The allele frequency (AF) of the prevalent DRB1 alleles were DRB1*0407 (48.4%), DRB1*0802 (33.9%) and DRB1*1402 (16.1%). The most frequent DQA1 and DQB1 alleles were DQA1*03011 (AF = 50.00%), DQA1*0401 (AF = 33.87%) and DQA1*0501 (AF = 16.13%); DQB1*0302 (AF = 50.00%), DQB1*0402 (33.87%) and DQB1*0301 (16.13%); which were in combination with DRB1*0407, DRB1*0802 and DRB1*1402, respectively. Three QAP and three QBP alleles were present (QAP 3.1, 4.1, 4.2; QBP 3.1, 3.21, 4.1) associated with the typical published DQA1 and DQB1 alleles. Four class II haplotypes were present in family members: DRB1*0407-QAP-3.1-DQA1*03011-QBP-3.21-DQB1*0302; DRB1*0802-QAP-4.2-DQA1*0401-QBP-4.1-DQB1*0402; DRB1*1402-QAP-4.1-DQA1*0501-QBP-3.1-DQB1*0301 and DRB1*0701-QAP-2.1-DQA1*0201-QBP-2.1-DQB1*0201. The family data were used to confirm extended haplotypes. A total of 21 haplotypes were found when A* and B* loci were also considered. The three most frequent combinations included A*0201-B*3501-DRB1*0407, A*3101-B*5101-DRB1*0802, and A*0201-B*40-DRB1*1402.

Distribution of TAP gene polymorphisms and extended MHC haplotypes in Mexican Mestizos and in Seri Indians from northwest Mexico.

The study of the genetic structure is very useful for investigating the biological significance of polymorphism and may provide clues to understand population origins. We present TAP1/TAP2 gene analysis in the Seri indians from Sonora, and in Mestizos from the highlands of Mexico. Thirty-two Seri and 89 Mestizos were studied. TAP genes were typed using the ARMS-PCR technique. The most frequent alleles in Seri were: TAP1*0101/02, (68.8%); TAP1*02011/02012, (31.2%); TAP2*0201, (38.7%) and TAP2*0101, (29.0%). TAP1*0301, TAP1*0401, TAP2*0102 TAP2*0103 and TAP2H were absent in them. For Mestizos, the prevalent alleles were: TAP1*0101/02 (75.8%); TAP1*02011/12 (20.3%); TAP2*0101 (45.4%) and TAP2*0201 (29.3%). These results are similar to those found in Kaingang and Caucasians from Brazil, four Mediterranean, other Caucasians, two Oriental and one African group. In Seri, the extended prevalent haplotypes are typically Amerindian, such as TAP1*0101/2-TAP2*0201-QBP3.21-DQB1*0302-QAP*3.1-DQA1*03011-DRB1*0407-B*3501-A*0201 (HF = 16.6%). Thirty-two extended haplotypes were found in Seri, although TAP contributed scarcely to diversity. Mestizos show Amerindian and Caucasian combinations. No difference was detected in the distribution of amino acids in the individual variable sites, between both groups. These findings are the basis for further anthropological studies and to explore the contribution of TAP genes to disease expression in Mexicans.

The genetic structure of Mexican Mestizos of different locations: tracking back their origins through MHC genes, blood group systems, and microsatellites.

Mexican Mestizos, who are the result of the admixture of Spanish, Indian, and Black genes, were analyzed for different systems. Three populations from geographical distinct areas were studied: the north (State of Nuevo Leon ), the center (State of Guanajuato), and the highlands (mainly Mexico City). Ten blood group systems (N = 229), STRs (N = 107), HLA-A*, B*, C* (N = 116-167), and DRB1, DQA1, and DQB1 (N = 40, 101, 160, respectively) were analyzed in the samples of the highlands. The three groups cluster together in the same branch: Mestizos from Venezuela, Mediterranean and Jews close to the cluster of Orientals, followed by Amerindians. All markers demonstrate that Indian genes are strongly represented in the highlands: Di(a), O, D(-)(+), s, A*0201, *0206, B*1539 (*1541), *3902, *3905, *3512, *3517, *4002, *4005, Cw*0801, *0304, *0401 among others. Cw*0501, *1203, *1204, and *1601 are of White ancestry. The most frequent haplotypes *0407-*03011-*0302 and *0802-*0401-*0402 are of Indian descent as well. The center and mainly the north show a more Caucasian and Semitic profile. The results demonstrate the high variability resulting from interethnic admixture, suggesting that this mechanism is the main factor responsible for the large diversity found in urban populations.

DQA1 and DQB1 promoter diversity and linkage disequilibrium with class II haplotypes in Mexican Mestizo population.

The upstream sequences in the 5' flanking region of HLA class II genes, regulate their expression and contribute to the development of immunological diseases. We analyzed 105 healthy unrelated Mexican Mestizos for QAP and QBP polymorphism. DNA typing for DRB1, DQA1, DQB1, QAP1 and QBP1 was done using a standardized PCR-SSOP. Although all QAP alleles previously described were found in Mexicans, the distribution differed as compared to other populations. QAP-3.1, 4.1 and 4.2 were the most frequent alleles and were associated with DQA1*03, *0501 and *0402 respectively. The prevalent QBP alleles were 3.21, 3.1 and 4.1 found mainly associated with DQB1*0302, *0301 and *0501. Linkage disequilibria between the promoter and the corresponding DQA1 and DQB1 allele, are in general the same as described by others. A total of 61 different haplotypes were defined, only six of them with a frequency above 4%. The haplotypes DRB1*0407-QAP-3.1-DQA1*03-QBP-3.21-DQB1*0302 (HF = 14.37%) and DRB1*0802-QAP-4.2-DQA1*0401-QBP-4.1-DQB1*0402 (HF = 14.22%), which have an Amerindian ancestry, are the most frequent in Mexicans. Some rare combinations were detected such as DRB1*0405-QAP-1.3-DQA1*0101/4-QBP-5.11/5.12-DQB1*0501 and DRB1*0403-QAP-3.2-DQA1*03-QBP-3.21-DQB1*0302, probably due to ancient recombination events. This knowledge is relevant as a basis to evaluate functional implications and to explore the role of promoter diversity in disease expression.

Contribution of HLA class II genes to end stage renal disease in mexican patients with type 2 diabetes mellitus.

To analyze the contribution of MHC class II genes in type 2 diabetes mellitus (DM) with end stage renal disease (ESRD), we examined the distribution of HLA-DRB1, DQA1, DQB1 loci in Mexican Mestizos of Central Mexico, using PCR-SSOP and PCR-SSP. Three groups were included: 47 type 2 diabetic ESRD patients; 42 patients with ESRD and 50 type 2 DM patients with no kidney complication. The results were compared with those of 101 controls of the same area. The median since DM was first diagnosed, was 18 years prior to the onset of ESRD. The frequencies of DRB1*1502 and DQB1*0501 were increased in DM patients with ESRD (p = 0.004; RR = 7.4, CI = 1.5-37; EF = 0. 13; p = 0.007; RR = 2.9, CI = 2.3-3.5, EF = 0.21, respectively). In contrast, DRB1*0407 was decreased in the same group (p = 0.0008, RR = 0.2; CI = 0.035-0.70, PF = 0.19). Diabetic patients with DRB1*1502 are 8.8 times more likely to develop ESRD, independently of the duration time of DM. DRB1*1502 contributes to the susceptibility to ESRD while DRB1*0407 is involved in protection. The residue at DRB1-74 differs in these alleles: DRB1*0407 has glutamic acid and DRB1*1502 has an alanine, suggesting that this substitution may be important for both, peptide anchoring and for presentation to the T cells.

Strong association of HLA class II sequences in Mexicans with Vogt-Koyanagi-Harada's disease.

Vogt-Koyanagi-Harada's syndrome (VKH) is an autoimmune disease prevalent in Mongoloids with evident participation of HLA. The aim of this study was to identify the class II DNA sequences involved in the etiopathogenesis of VKH in Mexican Mestizos. This study included 46 VKH patients and 170 controls. 75% were females (mean age at onset of 33.5 years). The disease evolved to chronicity (68%) and 25% of the patients were unresponsive to corticotherapy. DNA typing of HLA-DRB1, DQA1 and DQB1 was done following the 12th International Histocompatibility protocols. VKH was strongly dependent of DRB1 gene; DRB1*04 was found in 78.2% of the patients vs. 50.6% of the controls (p = 0.001). No particular DRB*04 subtype was significantly increased, suggesting that residues E-9 V-11; H-13; H-33 and Y-37 shared by all DR4s are implicated in susceptibility to VKH. However DRB1*0101 (p = 0.009, OR = 4.2) was clearly associated. This allele shares the motif LLEQRRAAG located at position 67-74 and 86 of DRB1 with *0405 associated in Japanese. Two HLA associated mechanisms may be triggering the autoimmune phenomena. One involving critical polymorphic residues expressed in different alleles. Secondly, some peptides may anchor to the conserved residues leaving other sequences to bind to the T cell receptor.

Molecular analysis of HLA class I alleles in the Mexican Seri Indians: implications for their origin.

The molecular analysis of HLA class I loci has demonstrated that, although, the genetic profile is restricted in Amerindians, several micropolymorphisms may be important in conferring a biological advantage. We analyzed the HLA-A and B genetic profile of Seris, a Mexican Indian tribe living in northwestern Mexico in the state of Sonora. There are presently only 619 individuals. Our study included 100 Seris belonging to nine families. HLA-A and -B loci typing was performed by polymerase chain reaction using an amplification refractory mutation system (PCR-ARMS) on a select group of samples; all of them were typed by polymerase chain reaction using sequence-specific oliogonuoleotide probes (PCR-SSOP) at a low-intermediate resolution level. The correlation between the techniques was 100%. Only five HLA-A alleles and seven HLA-B alleles were found. A*0201, A*68, A*31, A*24, B*3501, B*40, B*51, B*3512 and B*15 were present in over 5% of the individuals. B*27052 was detected in 2%. B27 is absent in any other Mexican Indian groups previously studied. The presence of B27 may be the result of a founder effect due to different waves of southward migrations. The B-locus is more diverse and the prevalent haplotypes were: A*0201-B*3501, A*0201-B*40, A*0201-B*3512, A*31-B*51, A*68-B*3501 and A*68-B*40. This genetic profile is different from the pattern of other Mexicans. The phylogenetic tree suggests that Seris are more closely related to the Warao Indians from Venezuela, who live in a similar ecosystem, and to some groups of Argentina, than they are to the Mexican Lacandones who live in the jungle. These data emphasize the relevance of the interaction between genes and environment.

HLA DOA1 and DOB1 loci in Honduran women with cervical dysplasia and invasive cervical carcinoma and their relationship to human papillomavirus infection.

Molecular and epidemiological studies have demonstrated that certain types of human papillomavirus (HPV), mainly HPV-16 and HPV-18, are the primary causes of cervical cancer and its precursor lesions; there is now evidence for a clear association with specific HLA class I and class II loci contributing independently to the expression of cervical cancer. Among Honduran women carcinoma of the cervix is the most common type of cancer, and infections with high-risk HPV types are highly prevalent. To study the interactive role of viral-host genetics, we performed PCR amplification of DNA and sequence-specific oligonucleotide probe typing on cervical scrapes from 49 women [24 with cervical intraepithelial neoplasia stage III or cervical cancer (severe cases) and 25 with stage I or II cervical intraepithelial neoplasia (mild cases)] and 75 control subjects to look for possible associations between HPV and HLA class II DQA1 and DQB1 alleles in the development of dysplasias and invasive cancer. This analysis revealed a predominance of HLA-DQA1*0301 among severe-case patients [relative risk (RR) = 3.45, p = 0.008), whereas DQA1*0501 was negatively associated (RR = 0.30, p = 0.03), suggesting a protective effect of this allele. HPV typing showed a decreased relative risk among the HPV-16 or HPV-18 carrying patients and other HPV-related positive patients in the presence of DQB1*0602 compared with positive control subjects (p = 0.04). No statistically significant allele frequency difference was observed between mild dysplasia cases and control subjects. The results suggest that DQA1*03011, which is in linkage desequilibrium with all HLA-DR4 alleles, confers an increased risk for severe cervical dysplasia and invasive cancer, whereas DQA1*0501, which is in several DR52 haplotypes, has a protective effect. Furthermore, specific HLA-DQB1 sequences may be important in determining the immune response to HPV peptides and may affect the risk for cervical cancer after HPV infection in mestizo Honduran women.

MHC class II sequences of susceptibility and protection in Mexicans with autoimmune hepatitis.

BACKGROUND/AIMS: Autoimmune hepatitis has a genetic background associated with different HLA DRB1 alleles depending on the ethnic group. The aim of this study was to analyse the immunogenetics of type I autoimmune hepatitis in Mexicans. METHODS: Thirty Mexican Mestizo patients and 175 healthy controls were HLA typed as follows: class I antigens were determined by microlymphocytotoxicity and class II typing was done on DNA samples using PCR-SSO and PCR-SSP for DRB1, DQA1 and DQB1 loci. RESULTS: A significant association of autoimmune hepatitis with DRB1*0404 was found, (chi2Y=19.95, pc=0.002, RR=7.71), suggesting the presence of a susceptibility gene located at the DRB1 locus. Resistance was at least partially due to a DQB1 gene, since a significant decrease in DQB1*0301 was also detected (chi2Y=8.21, pc=0.04). Analysis of subgroups according to age at onset showed an association with DRB1*0404 (chi2Y=4.31, p=0.04) in patients with late onset (after 30 years), while DQA1*0501 (chi2Y=5.12, p=0.02) was increased in the early onset group. CONCLUSIONS: The possible mechanism of HLA association is due to "shared epitopes", since DRB1*0404, and those found in other populations namely, DRB1*0401, *0405 and *0301 share almost the same sequence at position 67-72 (LLEQRR, R or K at 71). Valine-86 is also relevant to the age at onset because DRB1*0404 is increased in the patients with an average age at onset of 32. These findings are relevant in determining which peptides in the liver are targets for T cells.

HLA-DRB1*08 influences the development of disease in Mexican Mestizo with spondyloarthropathy.

OBJECTIVE: HLA class II encoded factors may influence the phenotype of ankylosing spondylitis (AS). These include HLA DRB1*07 for peripheral arthritis, and polymorphism of the HLA-linked LMP2 locus and HLA DRB1*08 for acute anterior uveitis (AAU). We studied the relationship between DRB1*08 and disease phenotype in additional populations of individuals with AS. METHODS: The patient population included 385 unrelated HLA-B27 positive individuals with AS. These included 204 Caucasians and 2 populations of Mexican Mestizo with AS: 106 with predominately adult onset disease from Guadalajara and 75 with predominately juvenile onset disease from Mexico City. The control population of 428 individuals included 210 random and 36 HLA-B27 positive unrelated Canadian Caucasians and 173 random and 9 HLA-B27 positive Mexican Mestizo from Mexico City. DRB1*08 typing was by sequence specific polymerase chain reaction. RESULTS: A significantly higher prevalence of DRB1*08 was observed in Mexican patients with juvenile onset disease (44.9%) and especially those with undifferentiated spondyloarthropathy (55.6%) compared to normal unrelated Mexican Mestizo (25.4%) (p < 0.01 for both) and in patients with undifferentiated spondyloarthropathy versus B27 controls (11.1%) (p = 0.03), although no significant differences were observed in within patient group comparisons based on phenotypic features of disease such as AAU and age at onset. No significant relationship between DRB1*08 and disease phenotype was evident in Caucasian individuals. CONCLUSION: Our data suggest DRB1*08 may influence the phenotype of spondyloarthritis in Mexican Mestizo, but do not support the view that DRB1*08 influences the development of AAU, as reported in a Japanese population.