Genetic analysis of a Chinese pedigree with an allele dropout at the HLA-B locus / 中华医学遗传学杂志

OBJECTIVE@#To delineate a deletional mutation of the HLA-B gene in a Chinese pedigree.@*METHODS@#A female patient with acute myeloid leukemia who had visited Liuzhou People's Hospital in April 2022 was selected as the study subject. Routine human leukocyte antigen (HLA) was determined by using PCR-sequence specific oligonucleotide polymorphism (PCR-SSOP) and PCR-sequence-based typing (PCR-SBT) methods. Next generation sequencing (NGS) was used to validate the candidate variant in the HLA-B gene.@*RESULTS@#The PCR-SBT and SSOP results for the HLA-B locus were inconsistent for the patient and her daughter. The SSOP results of the two individuals were HLA-B*35:01, 40:02 and HLA-B*35:01, 40:01, respectively. However, the PCR-SBT results has indicated a mismatch with the nearest HLA-B*35:01 at exon 4. NGS results showed that the HLA-B*35:01 had a 9 bp deletion in the intron 5. The patient's husband was HLA-B*40:01, 58:01, which was normal.@*CONCLUSION@#The variant in intron 5 of the HLA-B gene in this pedigree has mapped to a primer-binding region for the SBT reagent, which has affected the accuracy of PCR-SBT results.

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.

Characterization of a rare HLA-C*08:84 allele and analysis of its 3-D molecular structure / 中华医学遗传学杂志

OBJECTIVE@#To verify a rare allele of human leukocyte antigen (HLA) and analyze its inheritance and 3D molecular structure.@*METHODS@#PCR-sequence-based typing, PCR-single strand oligonucleotide polymorphism and single allele-specific sequencing were carried out to characterize the rare HLA-C allele and its transmission in the family. Its protein structure was modeled by using SWISS-MODEL, Phyre2 and FATCAT software.@*RESULTS@#Analysis indicated that the rare allele (HLA-C*08:84) has transmitted from the proband's mother and has differed from HLA-C*08:01 by a single base (g.512G>C), resulting in substitution of an amino acid (p.Trp147Ser). Modeling of the 3D structure of the encoded protein indicated that the amino acid residue variation is located at the alpha 2 helix, which participates the formation of pocket F. Modeling of the structures of C*08:84, C*08:01, C*08:02, C*08:03 and C*08:22 has suggested significant variation in the peptide binding regions of the backbone, with root mean square errors being 1.70 nm, 1.79 nm, 0.71 nm and 1.70 nm, respectively.@*CONCLUSION@#A rare HLA-C*08:84 allele has been identified, and its clinical significance has been analyzed.

Optimization of HLA-B*27 ALLELE Genotyping by PCR-SSP

OBJECTIVES: HLA-B27 is strongly associated with ankylosing spondylitis (AS) and its presence helps to confirm AS diagnosis. Due to the high HLA polymorphism and the differentiated contribution of alleles and molecules encoded by them, HLA-B*27 allele identification is relevant in the clinical follow-up, diagnosis, and treatment of this spondyloarthropathy. Inexpensive genotyping techniques with high specificity and sensitivity are of great interest in histocompatibility laboratories. This work aimed to optimize HLA-B*27 genotyping by Polymerase Chain Reaction Sequence-specific Primer (PCR-SSP), which is an accessible and inexpensive technique. METHODS: The PCR-SSP was standardized using 26 HLA-B*27 positive and 3 HLA-B*27 negative samples previously defined by Polymerase Chain Reaction Sequence-specific Oligonucleotide Probes (PCR-SSOP) (medium resolution, One Lambda®) and primers described by Duangchanchot et al. (2009). For validating the technique, 397 samples were genotyped using PCR-SSP as well as PCR-SSOP. RESULTS: The PCR-SSP technique was standardized for identifying the alleles HLA-B*27:02, HLA-B*27:CAFRW (05/13/16/17/28/37/38/39/42), HLA-B*27:CAFRZ (08/26/40), HLA-B*27:09 and HLA-B*27:12, which were found in 90 positive samples (22.67%). There was 100% agreement between the two techniques for heterozygous samples; however, two homozygous samples could not be detected by PCR-SSP. CONCLUSION: The HLA-B*27 genotyping using PCR-SSP, an easy-to-use, specific, and affordable technique, was optimized for heterozygous samples. This technique may contribute to AS diagnosis.

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.

A systematic review on the influence of hla-b polymorphisms on hiv-1 mother-to-child-transmission

ABSTRACT Background: Mother-to-child-transmission (MTCT) is the main route of HIV-1 infection in children. Genetic studies suggest HLA-B alleles play an important role on HIV-1 transmission, progression, and control of HIV-1 infection. Objective: To evaluate which polymorphisms of HLA-B are involved in HIV-1 MTCT. Methods: Two independent reviewers performed a systematic review on search engines PubMed, Europe PMC, Cochrane, Scientific Electronic Library Online (SciELO), and Literatura Latino-americana e do Caribe em Ciências da Saúde (Lilacs), using the following key terms: "HIV infection", "HIV newborn", "HLA polymorphisms", "HLA-B", and "Mother to child transmission". All studies focusing on evaluation of HIV-1 MTCT, HIV infection evolution, and molecular analyses of HLA-B in children were selected. Results: Nine studies fulfilled the inclusion criteria. Sixteen HLA-B alleles groups were associated with HIV-1 infection; seven of them (43.8%) were related to slow disease progression or reduced risk of MTCT, while six (37.5%) alleles groups were linked to a faster progression of HIV infection in children and to increased risk of MTCT. The available evidence suggest that HLA-B*57 group allele is associated with slow disease progression, while HLA-B*35 group allele is associated to increased risk of MTCT and rapid disease progression in infected children. The role of HLA-B*18, B*58 and B*44 are still controversial because they were associated to both, protection against MTCT, and to higher HIV replicative capacity, in different studies. Conclusion: HLA-B*57 group allele can be protective against MTCT while HLA-B*35 groups alleles are consistently associated with HIV-1 MTCT.

Determinación del polimorfismo de HLA-A, -B y -DRB1 en donantes de órganos con muerte encefálica representativos de la población general colombiana, 2007-2014 / Determination of HLA-A, -B and -DRB1 polymorphism in brain dead organ donors representative of the Colombian general population, 2007-2014

Resumen Introducción. Los genes que codifican para el sistema de antígenos leucocitarios humanos (Human Leukocyte Antigen, HLA) son muy polimorfos y de gran importancia en procedimientos de trasplante de órganos, ya que la determinación de las frecuencias alélicas en poblaciones específicas se tiene en cuenta entre los criterios científicos para la asignación de órganos. Objetivo. Establecer las frecuencias antigénicas y haplotípicas de HLA-A, -B y -DRB1 en donantes de órganos con muerte encefálica, representativos de la población colombiana. Materiales y métodos. En este estudio descriptivo retrospectivo de 2.506 donantes cadavéricos de órganos, se hizo un análisis alélico y de haplotipos de HLA-A, -B y -DRB1, y se determinó el equilibrio de Hardy-Weinberg. Resultados. Se encontraron 21, 43 y 15 grupos alélicos para los loci A*, B* y DRB1*, respectivamente. Se detectaron 1.268 haplotipos HLA-A, -B y -DR, 409 haplotipos HLA A-B, 383 haplotipos HLA-B-DR y 218 haplotipos HLA-A-DR. Los tres loci se encontraban en equilibrio de Hardy-Weinberg entre el número de heterocigóticos observados y el esperado, con valores de p<0,05. Conclusiones. En este estudio se proporciona información sobre la distribución de los alelos HLA de clase I y II en la población de donantes de órganos provenientes de las seis regionales en las que está dividido el país para la prestación de servicios de trasplante.

Abstract Introduction: Genes encoding for human leukocyte antigens (HLA) are highly polymorphic and of great importance in organ transplantation procedures, as determining allelic frequencies in defined populations is taken into account among the scientific criteria for organ allocation. Objective: The objective of this study was to establish the antigen HLA-A, -B, and -DRB1 haplotype frequencies in organ donors representative of the Colombian population after brain death. Materials and methods: We conducted a descriptive retrospective study involving 2,506 cadaveric organ donors including an allelic and haplotype analysis of HLA-A, -B and -DRB1; we also determined the Hardy-Weinberg equilibrium. Results: We identified 21, 43 and 15 allelic loci for groups A*, B* and DRB1*, respectively. We detected 1,268 HLA-A, -B and -DR, 409 HLA-A-B, 383 HLA-DR-B, and 218 HLA-A-DR haplotypes. The three loci were found to be in Hardy-Weinberg equilibrium between the number of heterozygotes observed and the expected number, with p values of <0.05. Conclusions: This study provides information on the allelic distribution of HLA class I and II in organ donors from the six regions in which Colombia is structurally divided to provide transplant services.

Lack of association between alopecia areata and HLA class I and II in a southeastern Brazilian population

Abstract: Background: Alopecia areata (AA) is a common disorder of unknown etiology that affects approximately 0.7% to 3.8% of patients among the general population. Currently, genetic and autoimmune factors are emphasized as etiopathogenic. Studies linking Human Leukocyte Antigens (HLA) to AA have suggested that immunogenetic factors may play a role in the disease's onset/development. Objectives: To investigate an association between AA and HLA class I/II in white Brazilians. Methods: Patients and control groups comprised 33 and 112 individuals, respectively. DNA extraction was performed by column method with BioPur kit. Allele's classification was undertaken using the PCR-SSO technique. HLA frequencies were obtained through direct counting and subjected to comparison by means of the chi-square test. Results: Most patients were aged over 16, with no familial history, and developed partial AA, with no recurrent episodes. Patients showed a higher frequency of HLA-B*40, HLA-B*45, HLA-B*53 and HLA-C*04 compared with controls, although P was not significant after Bonferroni correction. Regarding HLA class II, only HLA-DRB1*07 revealed statistical significance; nevertheless, it featured more prominently in controls than patients (P=0.04; Pc=0.52; OR=0.29; 95%; CI=0.07 to 1.25). P was not significant after Bonferroni correction. Conclusions: The development of AA does not seem to be associated with HLA in white Brazilians, nor with susceptibility or resistance. The studies were carried out in populations with little or no miscegenation, unlike the Brazilian population in general, which could explain the inconsistency found.

HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. MATERIALS AND METHODS: We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. RESULTS: HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. CONCLUSION: HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.

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.

Relationship between complaints presented by emergency patients and the final outcome / Relação entre queixas apresentadas por pacientes na urgência e o desfecho final / Relación entre las quejas presentadas por pacientes en la urgencia y el desenlace final

AbstractObjective: to relate complaints presented by emergency room patients, classified using the Manchester Triage System, with the final outcome (discharge/death/transfer).Methods: prospective cohort study, involving 509 patients who were admitted to the emergency room and remained there for more than 24 hours after admission, being monitored to the final outcome. Data were analyzed with a statistical program using descriptive and analytical statistics.Results: the mean age of the patients was 59.1 years and 59.3% were male. The main complaints were unwell adult (130 - 22.5%), shortness of breath in adults (81 - 14.0%), abdominal pain in adults (58 - 10.0%) and behaving strangely (34 - 5.9%), with 87% of the patients being discharged. More deaths were found in the patients classified in the severe colors, with 42.8% classified as red, 17.0% as orange and 8.9% as yellow. Among the patients classified as green, 9.6% died.Conclusion: in the various colors of the Manchester Triage System, death prevailed in patients that presented the complaints of unwell adult, shortness of breath, head injury, major trauma, diarrhea and vomiting. The higher the clinical priority the greater the prevalence of death.

ResumoObjetivo:relacionar queixas apresentadas pelos pacientes classificados pelo Sistema de Triagem de Manchester em um pronto-socorro com o desfecho final (alta/óbito/transferência).Métodos:estudo de coorte prospectivo, realizado com 509 pacientes que deram entrada no pronto-socorro e que nele permaneceram por mais de 24 horas após a admissão, sendo acompanhados até o desfecho final. Os dados foram digitados e analisados com estatística descritiva e analítica em um pacote estatístico.Resultados:entre os pacientes, 59,3% eram do sexo masculino, com idade média de 59,1 anos. As queixas principais eram de mal-estar no adulto (130-22,5%), dispneia em adulto (81-14,0%), dor abdominal em adulto (58-10,0%), alterações de comportamento (34-5,9%), sendo que, desses, 87% recebeu alta. Foram encontrados mais óbitos nos pacientes classificados nas cores mais graves, sendo 42,8% classificados como vermelho, 17,0% laranja e 8,9% como amarelo. Entre os pacientes classificados como verde, 9,6% evoluiu para óbito.Conclusão:nas diversas cores do Sistema de Triagem Manchester, o óbito prevaleceu nos pacientes que apresentaram a queixa de mal-estar no adulto, dispneia, sofreram trauma craniano, trauma maior, diarreia e vômito. Quanto maior a prioridade clínica maior a prevalência de óbito.

ResumenObjetivo:relacionar las quejas presentadas por los pacientes clasificados por el Sistema de Clasificación de Manchester, en un servicio de urgencia, con el desenlace final (alta/muerte/ transferencia).Métodos:estudio de cohorte prospectiva, realizado con 509 pacientes que dieron entrada en el servicio de urgencia y que en él permanecieron por más de 24 horas después de la admisión, siendo seguidos hasta el desenlace final. Los datos fueron introducidos y analizados con estadística descriptiva y analítica, en un programa estadístico.Resultados:entre los pacientes, 59,3% eran del sexo masculino, con edad promedio de 59,1 años. Las quejas principales eran de malestar en adulto (130-22,5%), disnea en adulto (81-14,0%), dolor abdominal en adulto (58- 10,0%), alteraciones de comportamiento (34-5,9%), siendo que, de estos, 87% recibió alta. Fueron encontradas más muertes entre los pacientes clasificados con los colores más graves, siendo 42,8% clasificados como rojo, 17,0% naranja y 8,9% como amarillo. Entre los pacientes clasificados como verde, 9,6% evolucionó para la muerte.Conclusión:en los diversos colores del Sistema de Clasificación Manchester, la muerte prevaleció en los pacientes que presentaron la queja de malestar en adulto, disnea, sufrieron trauma craniano, trauma mayor, diarrea y vómito. Cuanto mayor es la prioridad clínica mayor es la prevalencia de la muerte.

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. .

Drug Eruptions Induced by Allopurinol Associated with HLA-B*5801.

Allopurinol, a drug commonly used for treating gout and hyperuricemia, is a frequent cause of drug eruptions. Recent investigations suggest that HLA‑B*5801 allele is a very strong marker for allopurinol‑induced cutaneous adverse drug reactions (cADRs). In this article we report two cases of allopurinol‑induced drug eruptions in patients carrying the HLA‑B*5801 allele and review the literature on the association between HLA‑B*5801 and allopurinol‑induced cADRs based on a MEDLINE and PubMed search.

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.

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.

HLA-B*5701 frequency in Chilean HIV-infected patients and in general population

It has been demonstrated that HLA-B*5701 screening reduces the risk for hypersensitivity reaction to abacavir in HIV-infected patients. Since B*5701 prevalence varies among different populations, it is important to determine the carrier frequency prior to its use for the screening of HIV-infected patients.The aim of this study was to determine HLA-B*5701 carrier frequency in Chilean general population and HIV-infected patients referred for B*5701 typing. For that purpose 300 blood bank donors and 492 abacavir-naïve HIV-infected patients from Chile were screened for B*5701 by a sequence specific primer PCR.We detected 14/300 (4.7 percent) B*57-positive individuals in the Chilean general population, 11 (3.7 percent) were B*5701 positive, and 3 (1 percent) had another subtype.All were heterozygous,thus a B*5701 allele frequency of 2 percent was determined.Eleven of 492 (2.2 percent) HIV-patients carried a B*5701 allele. The difference between these frequencies is probably due to slow progression of HIV infection in HLA-B*5701 carriers, thus less patients would require antiretroviral therapy and B*5701 typing. Considering the usefulness of B*5701 screening, its prevalence in the Chilean general population,and the availability of a validated method,we conclude that HLA-B*5701 typing in Chilean HIV-infected patients about to initiate abacavir treatment is strongly recommended.

Molecular analysis of human leukocyte antigen class I and class II allele frequencies and haplotype distribution in Pakistani population.

AIM: Distribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations. MATERIALS AND METHODS: HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay. RESULTS: The most frequent class I alleles observed were A*02, B*35 and CW*07, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 *03, *07, *11 and *15. The rare DRB1 alleles detected in this study were HLADRB1 *08 and *09, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1*15-DQB1*06 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype A*33-B*58-Cw*03 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid. CONCLUSION: Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region.