Analysis of Gene Recombination between HLA-B and -DRB1, HLA-DQB1 and -DPB1 Loci / 中国实验血液学杂志

OBJECTIVE@#To investigate the recombinations within the human leukocyte antigen (HLA) region in two families.@*METHODS@#Genomic DNA was extracted from the peripheral blood specimens of the different family members. HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci were genotyped using polymerase chain reaction-sequence specific oligonucleotide probing technique (PCR-SSO) and next-generation sequencing technique. HLA haplotype was determined by genetic analysis of the pedigree.@*RESULTS@#The haplotypes of HLA-A*11:01~C*03:04~B*13:01~DRB1*12:02~DQB1*03:01~DPB1*05:01:01G and HLA-A*03:01~C*04:01~B*35:03~DRB1*12:01~DQB1*03:01~DPB1*04:01:01G in the family 1 were recombined between HLA-B and HLA-DRB1 loci, which formed the haplotype of HLA-A*11:01~C*03:04~B*13:01~DRB1* 12:01~DQB1*03:01~DPB1*04:01:01G. The haplotypes of HLA-A *02:06~C*03:03~B*35:01~DRB1*08:02~DQB1*04:02~ DPB1*13:01:01G and HLA-A *11:01~C*07:02~B*38:02~DRB1*15:02~DQB1*05:01~DPB1*05:01:01G in the family 2 were recombined between HLA-DQB1 and HLA-DPB1 loci, which formed the haplotype of HLA-A*02:06~C*03:03~B*35:01~ DRB1*08:02~DQB1*04:02~DPB1*05:01:01G.@*CONCLUSION@#The gene recombination events between HLA-B and -DRB1, HLA-DQB1 and -DPB1 loci were found respectively in two Chinese Han families.

Analysis of loss of heterozygosity at HLA loci in a patient with leukemia / 中华医学遗传学杂志

OBJECTIVE@#To detect loss of heterozygosity (LOH) at human leukocyte antigen (HLA) loci in a Chinese patient with leukemia after haploidentical hematopoietic stem cell transplantation.@*METHODS@#HLA genotyping was carried out on peripheral blood, hair follicle and buccal swab samples derived from the patient after the transplantation as well as peripheral blood samples from his parents by using PCR-sequence specific oligonucleotide probe method and PCR-sequence based typing method. Short tandem repeat (STR) loci were detected by using a 23 site STR assay kit and a self-developed 6 STR loci assay for the HLA regions.@*RESULTS@#After the transplantation, the HLA genotype of the peripheral blood sample of the patient was identical to his father. The patient was HLA-A*02:01,24:02, C*03:03,03:04, B*13:01,15:01, DRB1*08:03,12:02, DQB1*03:01,06:01 for his hair follicle specimen. However, homozygosity of the HLA loci was found in his buccal swab sample. Only the HLA-A*24:02-C*03:03-B*15:01-DRB1*08:03-DQB1*06:01 haplotype from his father's was present, while the HLA-A*02:01-C*03:04-B*13:01-DRB1*12:02-DQB1*03:01 haplotype from his mother was lost. After the transplantation, the alleles of the 23 STR sites in the patient's peripheral blood sample were consistent to his father, with no allelic loss detected in his buccal swab sample. However, at least 4 STR loci in the HLA region were lost in his buccal swab sample.@*CONCLUSION@#LOH at the HLA loci has been detected in the buccal swab sample of a patient with leukemia who received haploidentical hematopoietic stem cell transplantation.

HLA alleles in renal transplant recipients with nonmelanoma skin cancer in southeastern Brazil

Abstract: Background: Renal transplant recipients are submitted to immunosuppression to avoid graft rejection, which makes them susceptible to various conditions. Furthermore, these individuals present malignant tumors more frequently than the general population, including nonmelanoma skin cancer. The individual genetic basis that acts in the pathogenesis of cutaneous cancer may present a protection or susceptibility factor for disease development. One of these factors is the HLA complex. Objective: To investigate HLA alleles association to the occurrence of nonmelanoma skin cancer in renal transplant recipients from São Paulo State. Methods: A total of 213 patients (93 renal transplant recipients with nonmelanoma skin cancer and 120 renal transplant recipients without nonmelanoma skin cancer) were evaluated by retrospective and cross-sectional study. Epidemiological, clinical and HLA typing data were found in databases. HLA class I (A, B) and class II (DR) alleles were compared to establish their association with nonmelanoma skin cancer. Results: Comparing renal transplant recipients with and without nonmelanoma skin cancer, the HLA-B*13 allele was associated with higher risk of developing nonmelanoma skin cancer while B*45 and B*50 alleles were associated with protection. Study limitations: The HLA A, B and DR alleles identification for the kidney transplantation routine is done by low and medium resolution techniques that do not allow discrimination of specific alleles. Conclusion: The involvement of HLA alleles in nonmelanoma skin cancer in renal transplant recipients was confirmed in this study. Renal transplant recipients with HLA-B*13 showed higher risk for developing a skin cancer (OR= 7.29) and should be monitored for a long period of time after transplantation.

Associação de alelos HLA e aborto espontâneo recorrente em uma população de São Luís/Maranhão, na região Nordeste do Brasil / HLA alleles association and recurrent spontaneous abortion in a São Luis/Maranhão population, in Brazilian Northeastern region

Investigar a associação dos alelos HLA-A, -B e -DRB1 com a ocorrência de Aborto Espontâneo Recorrente.

Rio Grande do Norte, Brazil, voluntary bone marrow donors registry analysis / Análise do registro de doadores voluntários de medula óssea do Rio Grande do Norte, Brasil.

Objective: this study aimed to report the allele and haplotype frequencies of volunteer bone marrow donors (VBMD) from the state of Rio Grande do Norte (RN) who were enrolled in the Brazilian Volunteer Bone Marrow Donor Registry (REDOME). Methods: the sample comprised 12,973 VBMD who had their allele and haplotype frequencies calculated by Arlequin 3.5.1.2. A multivariate analysis of the data was obtained through a principal component analysis (PCA) and hierarchical cluster analysis (HCA) performed with SPSS 8.0. Results: the most frequent allelic group was HLA-A*02, followed by -DRB1*13, -DRB1*04, -DRB1*07, -B*44, -B*35, -A*24 and -DRB1*01. Of the 2,701 haplotypes observed, the three most frequent were HLA-A*01 B*08 DRB1*03 (1.62%), -A*29 B*44 DRB1*07 (1.56%) and -A*02 B*44 DRB1*04 (1.29%). These haplotypes were in linkage disequilibrium. RN allele and haplotype frequencies were very similar to those in other Brazilian states in which similar studies have been performed. The PCA revealed that RN is highly genetically similar to Caucasian populations, especially those from Iberian countries, which strongly influenced the state’s ethnic composition. Africans and Amerindians also influenced the RN population structure, to a lesser extent. Conclusion: the HCA reinforced the conclusion that, despite its highly admixed profile, the RN population is genetically similar to European and European-descended populations. The PCA also showed that RN cities do not contribute to the same extent to REDOME, with less populous cities being underrepresented, indicating the need to enroll more VBMD from these smaller cities to faithfully depict the state’s population structure in the database. .

Objetivo: relatar as frequências alélicas e haplotípicas do HLA-A, -B e -DRB1 de doadores voluntários de medula óssea (DVMO) do Rio Grande do Norte (RN), inscritos no Registro Nacional de Doadores de Medula Óssea (REDOME). Metodologia: 12.973 DVMO tiveram suas frequências alélica e haplotípica calculadas pelo programa Arlequin 3.5.1.2. Uma análise multivariada dos dados foi obtida por meio da Análise de Componente Principal (ACP) e da Análise de Cluster Hierárquico (ACH) realizadas pelo SPSS 8.0. Resultados: os grupos alélicos mais frequentes foram HLA-A*02, seguido por -DRB1*13, -DRB1*04, -DRB1*07, -B*44, -B*35, -A*24 e -DRB1*01. Dos 2.701 haplótipos observados, os três mais frequentes foram HLA-A*01 B*08 DRB1*03 (1,62%), -A*29 B*44 DRB1*07 (1,56%) e -A*02 B*44 DRB1*04 (1,29%), que se encontravam em desequilíbrio de ligação. As frequências alélicas e haplotípicas do RN são bastante similares às de outros estados brasileiros em que trabalhos semelhantes foram executados. A ACP revelou ser o RN geneticamente muito semelhante a populações caucasianas, especialmente a dos países ibéricos, os quais influenciaram fortemente na composição étnica do Estado. Africanos e ameríndios também contribuíram para a estrutura populacional, mas em menor proporção. Conclusão: a ACH reforçou a conclusão de que, apesar de seu perfil miscigenado, a população do RN se assemelha geneticamente com populações europeias e que descendem das europeias. A ACP também mostrou que as cidades do RN não contribuem equitativamente na composição do REDOME, de modo que cidades pouco populosas estão sub-representadas, apontando a necessidade de cadastrar mais DVMO dessas cidades para que a estrutura da população seja fielmente retratada. .

Genetic diversity among volunteer donors of bone marrow in southeastern Brazil, according to the HLA system / Diversidade genética entre doadores voluntários de medula óssea no sudeste do Brasil, segundo o sistema HLA

CONTEXT AND OBJECTIVE: Checking the histocompatibility of the molecules of the human leukocyte antigen (HLA) system is vital for performing bone marrow transplantation with allogeneic material. The objective of this study was to characterize bone marrow donors according to gender, age, ethnicity and HLA groups at a regional hemotherapy center in Brazil. DESIGN AND SETTING: Descriptive study on registered donors at a regional hemotherapy center in a public university hospital in the southeastern region of Brazil. METHODS: The records of 66,780 donors who were registered between 2005 and June 2011 were consulted, and the variables studied were tabulated. RESULTS: There were equal numbers of male and female donors and 82.8% of them were under 45 years of age. In terms of ethnicity, 77.3% declared themselves to be white, 15.0% mixed race, 5.7% black and 2% others. In terms of immunogenetic characterization, the most frequent HLA-A allelic group was HLA-A*02, with 39.20% of the donors; in the HLA-B allelic group, the most common was HLA-B*35, with 14.18%; while in the HLA-DRB1 allelic group, the most frequent was HLA-DRB1*03, with 17.03%. Comparison between these results and data from the Brazilian Bone Marrow Donor Registry (REDOME) showed that there were demographic and immunogenetic differences due to the history of immigration in the region of Ribeirão Preto, in southeastern Brazil. CONCLUSIONS: The results reinforce the importance of understanding the demographic and immunogenic profile of regions of Brazil, in order to reduce the waiting time for a histocompatible donor. .

CONTEXTO E OBJETIVO: Para a realização de transplantes de medula óssea com material alogênico, é necessária a verificação de histocompatibilidade das moléculas do sistema HLA (human leukocyte antigen), fundamental para o sucesso desses transplantes. O objetivo desta pesquisa foi caracterizar os doadores de medula óssea segundo gênero, idade, etnia e grupos HLA de um centro regional de hemoterapia brasileiro. TIPO DE ESTUDO E LOCAL: Estudo descritivo dos doadores cadastrados em um centro regional de hemoterapia de um hospital público universitário da região Sudeste do Brasil. MÉTODOS: Foram consultadas as fichas dos 66.780 doadores cadastrados entre 2005 e junho de 2011 e tabuladas as variáveis estudadas. RESULTADOS: Encontrou-se distribuição equilibrada entre os gêneros, e 82,8% dos doadores tinham até 45 anos de idade. Quanto à etnia auto-referida, 77,3% se apresentaram como brancos, 15,0% como pardos, 5,7% como negros, os 2% restantes dividindo-se em outras etnias. Quanto à caracterização imunogenética, no grupo alélico HLA-A, o mais frequente foi o HLA-A*02, com 39,20%; no grupo alélico HLA-B, o mais comum foi o HLA-B*35, com 14,18%; no grupo alélico HLA-DRB1, o mais frequente foi o HLA-DRB1*03, com 17,03% do total de doadores. Quando esses resultados são comparados com os dados do cadastro nacional de doadores (REDOME), observam-se diferenças demográficas e imunogenéticas, que se explicam pelo histórico de imigração da região de Ribeirão Preto, no Sudeste brasileiro. CONCLUSÕES: Os resultados encontrados reforçam a importância de conhecer o perfil demográfico e imunogenético das regiões do Brasil, para reduzir o tempo de espera por um doador histocompatível. .

Absence of HLA-B*1502 and HLA-A*3101 Alleles in 9 Korean Patients With Antiepileptic Drug-Induced Skin Rash: A Preliminary Study

There have been a number of studies about correlations between HLA genotypes in various ethnic groups and occurrence of various cutaneous adverse drug reactions, ranging in intensity from mild to severe, caused by antiepileptic drugs (AEDs). This is the first report analyzing the HLA genotypes of 9 Korean patients with skin rashes induced by various AEDs. The AEDs that induced skin rash were lamotrigine (n=3), carbamazepine (n=3), oxcarbazepine (n=1), phenobarbital (n=1), and phenytoin (n=1). None of the patients' HLA genotypes was either HLA-B*1502 or HLA-A*3101. Based on these series of cases, AED-induced skin rash can occur independently of HLA-B*1502 or HLA-A*3101 genotypes in the Korean patients.

HLA-A*31 como marcador de suscetibilidade genetica em sepse / HLA-A*31 as a marker of genetic susceptibility to sepsis

Objetivo: Haplótipos do HLA têm sido associados a muitas doenças autoimunes, mas não foi descrita qualquer associação na sepse. O objetivo desse estudo é investigar o sistema HLA como um possível marcador de suscetibilidade genética à sepse. Métodos: Estudo prospectivo de coorte, incluindo pacientes admitidos em unidade de terapia intensiva e controles-saudáveis obtidos em lista de doadores de transplante renal. Foram excluídos pacientes abaixo dos 18 anos de idade, gestantes ou HIV positivos, pacientes com doença maligna metastática ou sob quimioterapia, pacientes com hepatopatia avançada, com condições de fim de vida. O DNA foi extraído de sangue total, e a haplotipagem de HLA foi realizada com a tecnologia MiliPlex®. Resultados: Foram incluídos 1.121 pacientes (1.078 doadores de rim, 20 pacientes com sepse grave e 23 pacientes admitidos por choque séptico) entre outubro de 2010 e outubro de 2012. Os participantes positivos para HLA-A*31 tiveram risco aumentado de desenvolver sepse (OR: 2,36 IC95%: 1,26-5,35). Não foi identificada outra associação significativa, quando considerado como nível de significância o valor de p<0,01. Conclusão: A expressão de HLA-A*31 está associada ao risco de desenvolvimento de sepse. .

Objective: The HLA haplotype has been associated with many autoimmune diseases, but no associations have been described in sepsis. This study aims to investigate the HLA system as a possible marker of genetic sepsis susceptibility. Methods: This is a prospective cohort study including patients admitted to an intensive care unit and healthy controls from a list of renal transplant donors. Patients with less 18 years of age; pregnant or HIV positive patients; those with metastatic malignancies or receiving chemotherapy; or with advanced liver disease; or with end-of-life conditions were excluded. The DNA was extracted from the whole blood and HLA haplotypes determined using MiliPlex® technology. Results: From October 2010 to October 2012, 1,121 patients were included (1,078 kidney donors, 20 patients admitted with severe sepsis and 23 with septic shock). HLA-A*31 positive subjects had increased risk of developing sepsis (OR 2.36, 95%CI 1.26-5.35). Considering a p value <0.01, no other significant association was identified. Conclusion: HLA-A*31 expression is associated to risk of developing sepsis. .

A comparison of Fulani and Nadar HLA.

Here recent studies of Nadar and Fulani HLA-A and HLA-B were compared to determine if these populations were related. The analysis revealed that the Nadar and Fulani populations share a number of unique alleles including A*101, A*0211, A*03011, A*3303, B*3501, B*3701, and B*51011. The study suggests a former residence of these diverse populations in same geographical area.

Allelic and Haplotypic Diversity of HLA-A, -B, -C, and -DRB1 Genes in Koreans Defined by High-resolution DNA Typing / 대한진단검사의학회지

BACKGROUND: In this study, we used high-resolution DNA typing to investigate the distribution of HLA alleles and haplotypes in Koreans. METHODS: HLA-A, -B, -C, and -DRB1 alleles were genotyped at the allelic (4-digit) level in 474 healthy Koreans. HLA genotyping was performed in two steps. Initially, serologic typing or generic-level DNA typing was performed using the PCR-sequence-specific oligonucleotide method, and then allelic DNA typing (exons 2 and 3 for class I, and exon 2 for DRB1) was carried out using the PCR-single-strand conformation polymorphism method or sequence-based typing. HLA allele and haplotype frequencies and linkage disequilibrium values were calculated by the maximum likelihood method using a computer program developed for the 11th International Histocompatibility Workshop. RESULTS: A total of 21 HLA-A, 40 HLA-B, 22 HLA-C, and 29 HLA-DRB1 alleles were found in Koreans. The most frequent alleles in each locus with frequencies of > or =10% were, in decreasing order of frequency, as follows: A*24:02, A*02:01, A*33:03; B*51:01; C*01:02, C*03:03; and DRB1*09:01. The numbers of two- and three-locus haplotypes with frequencies of >0.5% were as follows: 44 A-C, 42 B-C, 51 A-B, 52 B-DRB1, 42 A-C-B, and 34 A-B-DRB1. Thirteen A-B-DRB1 haplotypes with frequencies of > or =1.0% comprised 26.0% of the total haplotypes. The six most common haplotypes were as follows: A*33:03-B*44:03-DRB1*13:02 (3.7%), A*33:03-B*44:03-DRB1*07:01 (3.0%), A*33:03-B*58:01-DRB1*13:02 (3.0%), A*24:02-B*07:02-DRB1*01:01 (2.8%), A*30:01-B*13:02-DRB1*07:01 (2.3%), and A*11:01-B*15:01-DRB1*04:06 (2.2%). CONCLUSIONS: The information obtained in this study can be used as basic data for Koreans in the fields of organ transplantation, disease association, and anthropologic studies.

Association of HLA-A, B antigens with Susceptibility to Advanced Endometriosis in Koreans / 대한진단검사의학회지

BACKGROUND: Endometriosis is defined as the presence of endometrial tissue outside the uterus, causing diverse diseases, including infertility, pelvic pain, dysmenorrhea, and constipation. While there is a growing body of evidence that genetic and immunologic factors play important roles in the pathogenesis of the disease, HLA-A, B antigens have been reported to be associated with the risk of endometriosis in the Japanese population. This study was performed to determine whether the susceptibility to advanced endometriosis is also associated with HLA-A, B antigens in the Korean population, which is the closest ethnic group to Japanese. METHODS: We recruited 50 Korean patients with advanced endometriosis confirmed by surgical and histolological examinations. Distribution of HLA-A and B antigens was compared with that of 200 unrelated ethnically matched individuals. HLA-A and B genotyping was carried out using a PCRsequence specific oligonucleotide hybridization method. RESULTS: An increased frequency of B39 was observed in endometriosis patients compared with control subjects, but the difference was not statistically significant after correcting for multiple comparisons (4.0% patients vs 0.8% controls, OR=5.5, 95% CI=1.21-25.04, P=0.03, P(c)=not significant). No significant differences were found between the patients with endometriosis and the general control group with regards to the distribution of other HLA-A and B antigens. CONCLUSIONS: The findings of the present study suggest that the susceptibility to advanced endometriosis, unlike in the Japanese population, is not associated with HLA-A, B antigens in the Korean population.

HLA-A, -B and -DR allele and haplotype frequencies in Malays.

One thousand four hundreds and forty-five Malays registered with the Malaysian Marrow Donor Registry were typed for HLA-A, HLA-B and HLA-DR. Fifteen HLA-A, twenty nine HLA-B and fourteen HLA-DR alleles were detected. The most common HLA-A alleles and their frequencies were HLA-A24 (0.35), HLA-A11 (0.21) and HLA-A2 (0.15). The most common HLA-B alleles were HLA-B15 (0.26), HLA-B35 (0.11) and HLA-B18 (0.10) while the most common HLA-DR alleles were HLA-DR15 (0.28), HLA-DR12 (0.27) and HLA-DR7 (0.10). A24-B15-DR12 (0.047), A24-B15-DR15 (0.03) and the A24-B35-DR12 (0.03) were the most frequent haplotypes. This data may be useful in determining the probability of finding a matched donor and for estimating the incidence of HLA associated diseases.

HLA A, B, DR and DQ alleles study in Tunisian patients with atopic dermatitis

Background: Atopic dermatitis [AD] is a chronic inflammatory skin disease resulting from the interaction between envirommental and genetic factors. Many genes are involved in the etiopathology of AD, such as HLA genes

Objectives: Study the association between HLA-A, B, DR and DQ genes and the AD

Methods: HLA A and B genotyping were practised for 53 atopic dermatitis patients and 76 healthy controls using the microlymphotoxicity complement dependent technique, while HLA DR and DQ genetyping were practised for only 20 patients with AD and the controls by PCR-SSP method

Results: allelic frequency of HLA A32 was significantly increased in healthy individuals compared to patients affected with AD [p=0.02, RR=0.24]. HLA-B, DR and DQ showed no differences in distribution between patients and controls

Conclusion: Our study suggested that HLA-A32 could be a protective marker against atopic dermatitis for Tunisian patients, in contrast to HLA-B, DR and DQ alleles which seemed to have no importance in AD pathogenis

Evaluation of BioSewoom(TM) HLA-A, -B, -C PCR/SSP Kit / 대한진단검사의학회지

BACKGROUND: Human leukocyte antigen (HLA) typing based on polymerase chain reaction (PCR) is rapidly replacing the conventional serological method. This study was intended to evaluate Bio- SewoomTM HLA-A, -B, -C PCR/SSP kit (BioSewoom SSP) which had recently been developed in Korea. METHODS: A total of 158 samples from domestic (21) and international (137) HLA proficiency testing (PT) were genotyped with BioSewoom SSP, and its results were compared to consensus results. For comparison with INNO-LiPA HLA-A, -B, -C Typing Kit (INNO-LiPA, Innogenetics, Belgium), 20 samples of Koreans were genotyped with both kits for each HLA-A, -B, -C locus. RESULTS: Among the 21 samples of domestic PT, BioSewoom SSP showed ambiguities as follows: 4 samples (19.0%) in HLA-A, 6 (28.6%) in HLA-B, and 1 (4.8%) in HLA-C. The ambiguities could be resolved by considering the allele distribution of Koreans. Among the 137 samples from international PT, BioSewoom SSP also showed ambiguities as follows: 12 samples (8.8%) in HLA-A, 26 (19.0%) in HLA-B and 6 (4.4%) in HLA-C. Considering the allele distribution of Koreans, the serologic equivalents obtained from BioSewoom SSP showed a full agreement with those of INNO-LiPA in all the loci tested. Twelve (0.007%) among 1,760 PCR reactions from the 21 samples of domestic PT and 20 patient samples produced faint nonspecific bands, but it was negligible. PCR failure of internal control just barely occurred (15 PCR reactions, 0.009%), but it had no bearing on allele assignment. CONCLUSIONS: The performance of BioSewoom SSP was comparable to that of INNO-LiPA. All the ambiguities could be resolved by considering the allele distribution of Koreans. It is concluded that BioSewoom SSP has good performance to be used in routine HLA laboratories.

Analysis of HFE gene mutations and HLA-A alleles in Brazilian patients with iron overload

CONTEXTO E OBJETIVO: Hemocromatose é um distúrbio hereditário comum do metabolismo do ferro e uma das causas mais importantes de sobrecarga de ferro. O objetivo foi analisar a presença das mutações C282Y, H63D e S65C no gene HFE e dos alelos HLA-A em um grupo de pacientes brasileiros com sobrecarga de ferro e correlacionar o genótipo com variáveis clínicas e laboratoriais. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, na Disciplina de Hematologia e Oncologia. Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo. MÉTODOS: Estudamos 35 pacientes com sobrecarga de ferro atendidos em nosso ambulatório entre janeiro de 2001 e dezembro de 2003. Ferro sérico, ferritina sérica e capacidade total de ligação de ferro foram determinados por técnicas convencionais. As mutações C282Y, H63D e S65C do gene HFE e a determinação dos alelos HLA-A foram realizadas por reação de polimerase em cadeia (PCR). RESULTADOS: Vinte e seis dos 35 pacientes (74%) apresentavam pelo menos uma das mutações analisadas do gene HFE. Entre esses, cinco (14%) com genótipo C282Y/C282Y, 4 (11%) C282Y/H63D, 1 (3%) H63D/H63D, 6 (17%) C282Y/WT e 10 (29%) H63D/WT. Não foi encontrado nenhum paciente com a mutação S65C e 9 (26%) pacientes não apresentavam nenhuma das três mutações do gene HFE. Quatro dos 5 pacientes com genótipo C282Y/C282Y (80%) e 3 dos 4 pacientes C282Y/H63D (75%) eram HLA A*03. CONCLUSÃO: Análise das mutações do gene HFE constitui um importante procedimento na identificação de pacientes com hemocromatose hereditária, particularmente em pacientes com sobrecarga de ferro.

Typing class I HLA-A gene using a nested PCR-RFLP procedure

In order to detect several new HLA-A class I alleles that have been described since 1998, the original PCR-RFLP method developed to identify the 78 alleles recognized at that time at high resolution level was adapted by us for low and medium resolution levels using a nested PCR-RFLP approach. The results obtained from blood samples of 23 subjects using both the PCR-RFLP method and a commercial kit (MicroSSP1A®, One Lambda Inc.) showed an agreement higher than 95 percent. The PCR-RFLP adapted method was effective in low and medium resolution histocompatibility evaluations.

Polimorfismo do sistema HLA em uma amostra de mestiços da população de Teresina, Piauí / HLA polymorphism in a racially admixed sample of the population of Teresina, Piauí

OBJETIVO: Estabelecer as freqüências das especificidades HLA-A, B, DRB1 e DQB1 numa amostra de mestiços da cidade de Teresina, Piauí, para caracterizar a sua composição genética. MÉTODOS: A reação em cadeia da polimerase de seqüência de "primers" específicos (PCR-SSP) foi utilizada para determinar as especificidades HLA-A, B, DRB1 e DQB1 de 97 indivíduos mestiços, saudáveis e não relacionados da cidade de Teresina. A freqüência genotípica foi estimada e comparada com aquelas descritas em amostras de brasileiros caucasianos, portugueses, negros e índios utilizando a Análise de Componente Principal (PCA) e a Análise de Agrupamento Hierárquico (HCA). RESULTADOS: A freqüência das especificidades HLA-A, B, DRB1 e DQB1 observada na amostra de Teresina foi intermediária entre os caucasianos e negros e não foi observada freqüência elevada das especificidades típicas de populações ameríndias. A PCA e HCA demonstraram que os mestiços de Teresina estão muito próximos aos caucasianos e negros e não apresentam similaridades com os índios. CONCLUSAO: A composição genética do mestiço de Teresina é predominantemente bi-híbrida de genes de origem caucasiana e negra com pouca participação de genes indígenos.

HLA-A, -B, -DR en receptores de trasplante de médula ósea en Uruguay: Sistema Nacional de registro, tipificación y búsqueda de donantes de médula ósea y progenitores hematopoyéticos (SINDOME) / National System of Recording, Typification and Searching for spina cord donors and hematopoietic progenitors (SINDOME)

Uruguay posee un sistema solidario de financiación de trasplante a través del Fondo Nacional de Recursos y dedl banco Nacional de Órganos y tejidos (BNOT). En el trasplante alogénico de médula ósea la compatibilidad HLA es una barrera biológica importante. Las frecuencias alélicas y haplotípicas HLA son utilizadas para determinar la probabilidad de encontrar un donante con un fenotipo particualr HLA y para predecir el efecto de diversos esquemas de adjudicación basados en la compatibilidad en este sistema. El Laboratorio de Inmunogenética e Histocompatibilidad tipifica a todos los receptores y donantes del país. Se ha iniciado un programa cuyo objetivo central es organizar un sistema de registro, tipificación y búsqueda de donantes no relacionados a nivel nacional (SINDOME). Objetivos: analizar los receptores tipificados para trasplante de médula ósea (TMO) alogénico en nuestro servicio en el período enero 1997 - mayo 2002, y caracterizar la constitución genética del sistema HLA para 298 receptores. Material y método: en el lapso indicado se estudiaron 346 receptores y 1.083 donantes. Se realizó la tipificación HLA clase I por reacción de microlinfocitotoxicidad con anticuerpos monoclonales y la reversa, con nivel de resolución intermedio-alta. Se estimaron las frecuencias alélicas y haplotípicas en una muestra de 298 receptores. Resultados: de los 346 receptores de TMO estudiados en el marco del SINDOME, 58 por ciento es menor de 30 años. La relación donante-receptor fue de 3,13 pero sólo el 45 por ciento de los candidatos a trasplante tuvo un donante histocompatible. En el análisis del polimorfismo ded HLA-A, -B, -DR en la muestra de 298 receptores se encontró que los alelos más prevalentes fueron A2 (28,97 por ciento), B35 812,49 por ciento) y DR04 (15,24 por ciento). Sólo para el locus HLA-DRB1 la desviación del equilibrio de Hardy-Weinberg fue altamente significativa. Los haplotipos más comunes fueron A2-B51 y A2-B7 para HLA-A, -B, A2-DR11 y A2-DR04 para HLA-A -DRB1, y el haplotipo B8-DR03 para HLA-B -DR. De los Hplotipos HLA-A -B -DRB1, HLA-A1 -B8 -DR03 y HLA-A2 -B51 -DR13 fueron los más frecuentes. Conclusión: nuestros resultados demuestran que el sistema HLA presenta una considerable heterogeneidad, con un enorme polimorfismo y una amplia distribución de haplotipos. La posibilidad de encontrar donantes compatibles para un subgrupo de jóvenes con enfermedades malignas sin donantes familiares es muy baja.

Serologic heterogeneity of HLA-A24 correlates with allelic types in the Korean population

HLA-A24 is the second most frequently expressed HLA-A type in Koreans (GF 22.8%). Four different serologic reaction patterns were observed in Korean A24 positive samples using a commercial serologic typing kit. To clarify the nature of serologic heterogeneity, thirteen A24 positive DNA samples representing the four different serologic reaction patterns were subjected to DNA sequencing analysis of the amplified HLA-A genes from each sample. Four A*24 alleles (A*2402101, A*2403, A*2408, and A*2421) were associated with the four unique serologic reaction patterns. During this study, a novel allele, A*2421, was characterized. The new sequence is similar to A*2402101, differing at codon 127 (AAA-->AAC; K-->N). By comparing putative amino acid sequences and serologic reaction patterns of A*24 allelic products identified in this study, several crucial sites for A24- and A9-specific antibody binding were predicted: 127K for A24 antibody binding, and 62E-65G and 166D-167G for A9 antibody binding. This information will be helpful for accurately assigning HLA-A24 types by serology and for predicting serologic types of new alleles.

Estudio de los haplotipos HLA en leucemias / Study of HLA haplotypes in leukemias

Se determinaron las combinaciones alélicas de los genes HLA A y B en 144 pacientes con leucemias; 89 con leucemia linfoide aguda (LLA), 28 con leucemia mieloide aguda (LMA) y 27 con leucemia mieloide crónica (LMC), estraficados fenotípicamente en blancos, negros y mestizos, para evaluar la posible asociación entre los haplotipos HLA y esas enfermedades. Se utilizaron como controles 276 personas aparentemente estratificados también por el color de la piel. Los haplotipos A2-B12, A9-B12 y A2-B35 fueron los más frecuentes en el grupo total de enfermos y en los individuos blancos con LLA. La combinación de las especificidades A2 y B5 mostró un desequilibrio de asociación en el conjunto de enfermos y en los sujetos blancos con LMA