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Article in Chinese | WPRIM | ID: wpr-928415


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 Antigens/genetics , HLA-A Antigens/genetics , Histocompatibility Antigens Class I/genetics , Humans , Leukemia/genetics , Loss of Heterozygosity
Article in English | WPRIM | ID: wpr-880674


The human leukocyte antigen (HLA) molecules encoded within the human major histocompatibility complex are a group of highly conserved cell surface proteins, which are related to antigen recognition. HLA genes display a high degree of genetic polymorphism, which is the basis of individual differences in immunity. Specific HLA genotypes have been highly associated with typical adverse drug reactions. HLA-A*31:01 and HLA-B*15:02 are associated with carbamazepine-induced severe cutaneous adverse reactions, HLA-B*57:01 is related to abacavir-induced drug-induced hypersensitivity syndrome and flucloxacillin/pazopanib-induced drug-induced liver injury, while HLA-B*35:01 is a potential biomarker for predicting polygonum multiflorum-induced liver injury. It is not clear how small drug molecules to interact with HLA molecules and T cell receptors (TCR). There are four mechanistic hypotheses, including the hapten/prohapten theory, the pharmacological interaction concept, the altered peptide repertoire model, and the altered TCR repertoire model.

Drug-Related Side Effects and Adverse Reactions/genetics , Genotype , HLA Antigens/genetics , Humans , Polymorphism, Genetic
Gac. méd. Méx ; 155(3): 243-248, may.-jun. 2019. tab
Article in English, Spanish | LILACS | ID: biblio-1286499


Resumen Introducción: La enfermedad renal crónica representa parte del gasto en salud en general; una potencial etiología es la relacionada con variaciones, ausencia o presencia de algunos alelos del human leucocyte antigen (HLA). Método: Se realizó el análisis de 1965 reportes de HLA sin etiología determinada y de 1361 donadores renales. Se llevó a cabo tecnología Luminex con base en fluorimetría de flujo celular para los locus A, B, DRB1 y DQA. Se realizó análisis con tablas de contingencia para determinar razón de momios (RM) e intervalos de confianza (IC). Se efectuó análisis cuantitativo. Resultados: De 101 alelos encontrados, 13 presentaron asociación, siete con riesgo para enfermedad renal crónica, de los cuales el más significativo fue HLA-DR17, con RM = 3.91 (IC 95 % = 2.96-5.17), y el de mayor significación de protección fue HLA-DR9, con RM = 0.043 (IC 95 % = 0.005-0.3224). Conclusiones: Es necesario entender que las enfermedades renales pueden estar ligadas a procesos inmunológicos, en los que se tiene que conocer la asociación de la ausencia o presencia de algún alelo.

Abstract Introduction: Chronic kidney disease accounts for part of overall health expenditure; a potential etiology is related to variations, absence or presence of some human leukocyte antigen (HLA) alleles. Method: An analysis of HLA reports of 1965 kidney recipients with no determined etiology, and 1361 kidney donors was performed. It was carried out with Luminex based in cell flow fluorometry for the A, B, DRB1 and DQA loci. An analysis was performed with contingency tables in order to determine the odds ratio (OR) and confidence intervals (CI). Quantitative analysis was also carried out. Results: Of the 101 alleles found, 13 showed association, 7 with risk for chronic kidney disease, with the most significant being HLA-DR17 with an OR of 3.91 (95 % CI = 2.96-5.17) and the one with the highest significance for protection being HLA-DR9, with an OR of 0.043 (95 % CI = 0.005-0.3224). Conclusions: It is necessary to understand that kidney diseases can be associated with yet unknown immune processes, where the association of the absence or presence of any allele should be known.

Humans , Tissue Donors , Renal Insufficiency, Chronic/genetics , Transplant Recipients , HLA Antigens/genetics , Retrospective Studies , Risk Factors , Cohort Studies , Kidney Transplantation/methods , Alleles , Renal Insufficiency, Chronic/surgery , Protective Factors , Fluorometry
Rev. Assoc. Med. Bras. (1992) ; 65(6): 830-833, June 2019. graf
Article in English | LILACS | ID: biblio-1012983


SUMMARY OBJECTIVE Even though stress has been long known as a provocative factor for Graves' disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION This case demonstrates that, similarly to Graves' disease, Hashitoxicosis can also be triggered by stressful life events.

RESUMO OBJETIVO Mesmo que o estresse seja conhecido há muito tempo como um fator provocativo para a doença de Graves, sua relação com a tireoidite de Hashimoto é mais controversa. Estudos sobre esse tema são escassos. O objetivo deste artigo é relatar um caso de Hashitoxicose induzida por estresse. RESULTADOS Aqui nós relatamos um caso de Hashitoxicose induzido por um evento psicológico estressante em uma mulher de 28 anos com tireoidite de Hashimoto. Ela permaneceu estável eutireoidiana por 12 anos. Ela veio a nossa observação pela primeira vez em abril de 2016, enquanto eutireoidiana. Voltou após 11 meses por causa de fadiga e palpitações, na ausência de dor no pescoço. Testes de função tireoidiana revelaram uma tireotoxicose moderada (TSH indetectável; T4F 36,94 pmol/L, valores normais 9,0-24,46; FT3 13,50 pmol/L, valores normais 3,07-6,14) com anticorpos negativos para o receptor de TSH. Nos últimos três meses ela experimentou um evento psicológico estressante. Os marcadores inflamatórios foram negativos e a contagem de leucócitos foi normal. A ultrassonografia da tireoide revelou um aumento modesto da vascularização. Hipotireoidismo subclínico transitório ocorreu após sete semanas e se recuperou espontaneamente. Na última visita, a paciente ainda estava em eutireoidismo. (TSH 1,01 mU/L; FT4 9,22 pmol/L; FT3 3,98 pmol/L). Também realizamos a sorotipagem e a genotipização do HLA. CONCLUSÃO Este caso demonstra que, similarmente à doença de Graves, também a Hashitoxicose pode ser desencadeada por eventos estressantes da vida.

Humans , Female , Adolescent , Stress, Psychological/complications , Hashimoto Disease/psychology , HLA Antigens/genetics , Stress, Psychological/genetics , Thyroxine/blood , Thyrotropin/blood , Hashimoto Disease/genetics , Serogroup , Genotype
An. bras. dermatol ; 94(3): 287-292, May-June 2019. tab
Article in English | LILACS, SES-SP, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP | ID: biblio-1011110


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.

Humans , Male , Female , Adult , Middle Aged , Aged , Skin Neoplasms/genetics , Kidney Transplantation/adverse effects , HLA Antigens/genetics , Skin Neoplasms/etiology , Skin Neoplasms/epidemiology , Brazil/epidemiology , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-DR Antigens/genetics , Case-Control Studies , Cross-Sectional Studies , Retrospective Studies , Genetic Predisposition to Disease/genetics , Alleles , Transplant Recipients
Arq. neuropsiquiatr ; 77(4): 239-247, Apr. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001352


ABSTRACT Objective: To study the genetic susceptibility to neuromyelitis optica (NMO) as well as the relationship between HLA genotypes and susceptibility to the disease in the southern Brazilian population. Methods: We analyzed patients with NMO, who met criteria for Wingerchuk's diagnosis of NMO, with detected serum anti-AQP4-IgG antibody. The HLA genotyping was performed by high-resolution techniques (Sanger sequencing) in patients and controls. The HLA genotypes were statistically compared with a paired control population. Results: The HLA genotyping revealed the diversity of the southern Brazilian population whose HLA profile resembled European and Asian populations. Some alleles had statistical correlations with a positive association (increased susceptibility) with NMO, particularly the HLA-DRB1*04:05 and *16:02. Conclusions: In our study, the HLA genotype was different to that previously reported for other Brazilian populations. Although our study had a small cohort, HLA genotypes were associated with increased susceptibility to NMO for HLA-DRB1*04:05 and *16:02. The alleles of HLA class I HLA-A*02:08 and *30:09, HLA-B*08:04 and *35:04 showed an association before the Bonferroni correction.

RESUMO Objetivo: Estudar a suscetibilidade genética a neuromielite óptica (NMO) assim como sua relação com o genótipo HLA na população do sul do Brasil. Métodos: Nós analisamos pacientes com NMO que preenchiam os critérios diagnósticos de Wingerchuk para NMO, com presença do anticorpo anti-AQP4-IgG no soro. O genótipo HLA foi realizado usando técnicas de alta resolução (sequenciamento de Sanger) em pacientes e controles. Genótipos HLA foram estatisticamente comparados com uma população controle pareada. Resultados: Genotipagem HLA revelou a diversidade da população sul brasileira cujo perfil HLA lembra as populações europeia e asiática. Alguns alelos tiveram correlação estatística com associação positiva (suscetibilidade aumentada) com NMO, particularmente o HLA-DRB1*04:05 e *16:02. Conclusões: Em nosso estudo, o genótipo HLA foi diferente do previamente relatado em outras populações brasileiras. Embora o número de pacientes tenha sido pequeno, HLA específicos foram associados com suscetibilidade aumentada a NMO para HLA-DRB1*04:05, *16:02. Os alelos HLA classe I HLA*02:08 e *30:09, HLA-B*08:04 e *35:04 tiveram associação antes da correção de Bonferroni.

Humans , Male , Female , Adult , Middle Aged , Young Adult , Genes, MHC Class I/genetics , Neuromyelitis Optica/genetics , Genes, MHC Class II/genetics , Genetic Predisposition to Disease/genetics , Alleles , HLA Antigens/genetics , Reference Values , Brazil , Case-Control Studies , Polymerase Chain Reaction , Gene Frequency , Genotype
Einstein (Säo Paulo) ; 17(1): eAO4477, 2019. tab, graf
Article in English | LILACS | ID: biblio-984373


ABSTRACT Objective To described the allele and haplotype frequencies of human leukocyte antigen genes at the -A, -B loci and human platelet antigen genes for human platelet antigen systems 1 to 9, 11 and 15 in blood. Methods We included 867 healthy unrelated volunteer donors who donated platelets between January 2011 and December 2014. Microarray genotyping was performed using a BeadChip microarray. Medium resolution typing of the human leukocyte antigen at loci A and B was carried out using sequence-specific oligonucleotide probe hybridization. We used multivariate analysis and our human leukocyte antigen population was compared to data from the United States national bone marrow donor program. Human platelet antigen results were compared to a literature review and data from around the world. Results Our human leukocyte antigen haplotype results were more similar to those of hispanics, followed by caucasians. Likewise, our human platelet antigen sample is more similar to those of Argentina, Rio Grande do Sul and Italy. Conclusion This was the first article that discusses human platelet antigen and human leukocyte antigen data together. Rare genotypes or antibody associations can make patient management difficult. A blood bank with genotyped donors allows for optimal transfusion and can contribute to better results. Our information can serve as basis for a database of platelet antigen polymorphisms.

RESUMO Objetivo Descrever as frequências alélicas e haplotípicas de genes dos antígenos leucocitários humanos nos loci -A,- B e dos antígenos plaquetários humanos para os sistemas HPA-1 a 9, 11 e 15. Métodos Foram incluídos 867 doadores voluntários, saudáveis, não relacionados, que doaram plaquetas por aférese entre janeiro de 2011 e dezembro de 2014. A genotipagem foi realizada usando microarray BeadChip. A tipificação de resolução intermediária dos antígenos leucocitários humanos loci A e B foi realizada por meio de hibridização com sonda para oligonucleotídeos por sequência específica. Utilizamos análises multivariadas e o antígeno leucocitário humano de nossa população foi comparado com a do programa nacional de doadores de medula óssea norte-americano. Já os resultados dos antígenos plaquetários humanos foram comparados à revisão da literatura e a dados de populações de outros países. Resultados Os resultados do haplótipo de antígenos leucocitários humanos são mais parecidos com os dos hispânicos, seguidos dos caucasianos. Igualmente, a amostra de antígenos plaquetários humanos foi mais semelhante às da Argentina, do Rio Grande do Sul e da Itália. Conclusão Este foi o primeiro artigo a discutir antígenos plaquetários e leucocitários humanos simultaneamente. Genótipos raros ou associações de anticorpos podem dificultar o manejo clínico do paciente. Um banco de sangue com doadores genotipados permite um melhor resultado e transfusão possíveis. Estas informações podem servir de base para um banco de dados sobre polimorfismos de antígenos plaquetários.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Polymorphism, Genetic/genetics , Haplotypes/genetics , Antigens, Human Platelet/genetics , Alleles , Genotyping Techniques/methods , HLA Antigens/genetics , Tissue Donors , Platelet Transfusion , Gene Frequency/genetics , Genotype
Arq. neuropsiquiatr ; 76(10): 697-704, Oct. 2018. tab
Article in English | LILACS | ID: biblio-973921


ABSTRACT Objective: To investigate the potential relationship between the human leukocyte antigen (HLA) type (class I and II) and the response to several disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS). Methods: We analyzed clinical data of 87 patients with MS at the beginning and end of each type of DMT including the disease duration, Expanded Disability Status Scale and Multiple Sclerosis Severity Score (MSSS). Genotyping of HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B and HLA-C alleles were identified using high-resolution techniques. Statistical correlation between the HLA type and response to DMTs was done using the initial and final MSSS. Results: Statistical relationships (p < 0.05) were found for only 15 of 245 alleles tested. There was a reduction in the MSSS for patients treated with corticosteroids (DRB1*15:01, DPB1*04:01, DQB1*02:01 and DQB1*03:01), azathioprine (DRB1*03:01, DPB1*04:01, DQB1*03:02, DQB1*06:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 and DQB1*03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) and interferon β-1b (DQB1*02:01). Conclusion: These findings suggest a few relationships between the HLA and response to DMTs in the disability for some types of HLA class I and II alleles in a specific subset of MS patients.

RESUMO Objetivo: Investigação da possível relação entre os tipos dos antígenos leucocitários humanos (HLA) classes I e II e a reposta a diversas terapêuticas modificadores da doença na incapacidade (DMT) da esclerose múltipla (MS). Métodos: Foram estudados os dados clínicos de 87 pacientes com MS no início e no final de cada de cada DMT, incluindo o tempo de doença, EDSS e MSSS. Através de técnicas de genotipagem de alta resolução, foram identificados os alelos dos HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B e HLA-C. Foram realizados estudos estatísticos entre os tipos de HLA e a resposta às DMT, utilizando os valores iniciais e finais do MSSS. Resultados: Foram encontradas relações estatísticas (p < 0.05) para somente 15 alelos de 245 analisados. Houve redução dos valores do MSSS em pacientes tratados com corticosteroides (DRB1*15:01, DPB1*04:01, DQB1*02:01 e 03:01), azatioprina (DRB1*03:01, DPB1*04:01, DQB1*06:02, DQB1*03:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 e 03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) e interferon β-1b (DQB1*02:01). Conclusão: Os dados sugerem poucas relações entre os alguns tipos de HLA classe I e II com a resposta às DMT na incapacidade em grupos específicos de pacientes com MS.

Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Young Adult , Multiple Sclerosis, Relapsing-Remitting/genetics , HLA Antigens/genetics , Time Factors , Severity of Illness Index , HLA-D Antigens/genetics , Treatment Outcome , Disease Progression , Genetic Predisposition to Disease , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Alleles , Gene Frequency/genetics , Genotype , Immunosuppressive Agents/therapeutic use
Einstein (Säo Paulo) ; 13(1): 153-156, Jan-Mar/2015.
Article in English | LILACS | ID: lil-745865


The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function.

O cenário no qual ocorre a resposta imune é o da necessidade de fazer frente a uma vasta gama de antígenos diferentes, de fontes patogênicas e não patogênicas. Quando as primeiras barreiras contra infecção e a defesa inata falham, a resposta imune adaptativa entra em campo, para efetuar o reconhecimento dos antígenos, utilizando, para esse fim, moléculas extremamente variáveis, que são as imunoglobulinas e os receptores de células-T. Estes últimos reconhecem o antígeno, exposto na superfície das células como peptídeo apresentado pelas moléculas HLA. A primeira parte desta revisão detalha o papel central dessas moléculas, estabelecendo a conexão que existe entre a estrutura e a função de apresentação de antígenos.

Humans , Antigen Presentation/immunology , HLA Antigens/immunology , Major Histocompatibility Complex/immunology , Alleles , Antigen Presentation/genetics , HLA Antigens/genetics , Major Histocompatibility Complex/genetics
Article in English | WPRIM | ID: wpr-64362


BACKGROUND: The impact of HLA and KIR ligand mismatching on the outcome of hematopoietic stem cell transplantation (HSCT) remains unclear. Previous reports have identified considerable ethnic differences in the impact of HLA and KIR ligand mismatches, as well as KIR ligand status, on HSCT; however, to date, no data has been acquired in Korean adult patients. METHODS: We investigated the association of high-resolution HLA matching on five loci (HLA-A, -B, -C, -DRB1, and -DQB1), KIR ligand mismatching, and KIR ligand status on the outcome of allogeneic HSCT from unrelated donors in 154 Korean adult patients treated at Seoul National University Hospital. RESULTS: In a multivariate analysis, less than 9/10 allelic matches in five HLA loci was an independent risk factor for acute graft-versus-host disease (GVHD) (grade II to IV) (P=0.019, odds ratio [OR]=2.7). In addition, HLA-A allele mismatching was increasingly prevalent in patients with acute GVHD compared to patients without (61.9% vs. 34.5%, P=0.06). For KIR ligand status, the patient and donor combination of both C1/C1 ligands showed better event-free and overall survival than combinations with C2 ligand patients or donors (P=0.048, P=0.034, respectively) by log-rank test. CONCLUSIONS: Korean adult transplant patients with less than 9 of 10 HLA allele matches in the HLA-A, -B, -C, -DRB1, and DQB1 loci have a higher likelihood of developing acute GVHD (grade II to IV). Impact of KIR ligand status on clinical outcome should be further studied in a larger patient population.

Adolescent , Adult , Alleles , Female , Genetic Loci , Graft vs Host Disease/etiology , HLA Antigens/genetics , Hematopoietic Stem Cell Transplantation/adverse effects , Histocompatibility Testing , Humans , Kaplan-Meier Estimate , Leukemia/mortality , Male , Middle Aged , Multivariate Analysis , Receptors, KIR/chemistry , Republic of Korea , Risk Factors , Transplantation, Homologous , Young Adult
Säo Paulo med. j ; 132(3): 158-162, 14/abr. 2014. tab
Article in English | LILACS | ID: lil-710416


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. .

Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Bone Marrow , Genetic Variation , HLA Antigens/genetics , Registries , Tissue Donors , Age Factors , Bone Marrow Transplantation , Brazil , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-DRB1 Chains/genetics , Sex Factors
Recife; s.n; 2014. 84 p. ilus.
Thesis in Portuguese | LILACS | ID: lil-720604


Fatores genéticos e imunológicos foram associados à patogenese da doença inflamatória intestinal (DII), ela inclui Retocolite Ulcerativa Idiopática (RCUI) e doença de Crohn (CD). A hiperresponsividade de celulas B e a autoreatividade de células T contribuem para a polarização da resposta imune Th1 em CD e Th2 em RCUI. Sítios polimórficos na região 3'não traduzida do gene HLA-G (completa) e região promotora dos genes IL-10 ( - 1082A/G e - 819C/T) e TNF (completa) foram associados a susceptibilidade a diversas doenças. Estudamos 217 portadores de DII e 249 doadores saudáveis, pareados por sexo e idade. A ascendência africana foi maior em RCUI e caucasiana em DC (p =0,005). Comparados aos controles, o genótipo HLA - G 14bpINS - INS (associado com baixa expressão de HLA - G) (p =0,006) e IL - 10 - 1082G - G (associado com alta expressão de IL - 10) (p =0,030) foram menos frequentes em pacientes com DC, possivelmente contribuindo para a polarização Th1, mas não foram encontradas diferenças nas frequências de TNF. Em RCUI, as frequências do alelo HLA-G +3003C (p =0,015) e genótipo +3003C-T (p =0,003) estavam aumentadas. Apesar da alta frequência do alelo T em africanos, após estratifica rmos por ascendência, o genótipo +3003C - T ainda estava mais frequente em pacientes com ascendência africana (p =0,012)...

Genetic and immunological factors have been associated with inflammatory bowel disease (IBD) pathogenesis, encompassing ulcerative colitis (UC) and Crohn's disease (CD).B cell hyperresponsiveness and T cell auto-reactivity have contributedto a Th1 polarization immune response in CD and a Th2 polarization in UC. Sincepolymorphic sites at the 3’untranslated region (3’UTR)...

Colitis, Ulcerative/genetics , Colitis, Ulcerative/immunology , Crohn Disease/genetics , Crohn Disease/immunology , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/immunology , HLA Antigens/genetics , HLA Antigens/immunology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology , /genetics , /immunology
Yonsei Medical Journal ; : 1005-1013, 2014.
Article in English | WPRIM | ID: wpr-113974


PURPOSE: To evaluate a multi-group-specific sequence-based typing (SBT) method for resolving ambiguous results from human leukocyte antigen (HLA) genotyping. MATERIALS AND METHODS: A total of 50 samples that showed ambiguous genotypes for at least two HLA loci from HLA-A, -B, -C and -DRB1 by the conventional SBT assay were evaluated using a new SBT test, the AVITA plus assay. The most likely HLA genotypes for the respective samples considering allele frequencies in Korean were concordant between the AVITA and conventional SBT assays. RESULTS: An average of 3.3 loci among the HLA-A, -B, -C and -DRB1 loci per sample gave results with two or more possible allele combinations with the conventional SBT, and 48 (96.0%) out of 50 showed reduced numbers of possible genotypes for at least one HLA locus with the AVITA. A total of 41, 43, 42, and 38 cases among the 50 samples showed ambiguous results for HLA-A, -B, -C, and -DRB1 typing by the conventional SBT, respectively. The average numbers of possible allele combinations for the respective four HLA loci were 8.2, 6.7, 5.9, and 3.2, and they were reduced to 1.5, 2.2, 4.4, and 1.8, respectively, by the AVITA. Ambiguity was resolved by the AVITA in 33 (80.5%), 31 (72.1%), 17 (40.5%) and 28 (73.7%) samples among the ambiguous cases from the conventional SBT for HLA-A, -B, -C, and -DRB1 typing, respectively. CONCLUSION: The multi-group-specific SBT method considerably reduced the number of ambiguous results, and thus may be useful for accurate HLA typing in clinical laboratories.

Asians/genetics , Base Sequence , Gene Frequency/genetics , Genotype , HLA Antigens/genetics , Histocompatibility Testing , Humans , Polymerase Chain Reaction
Indian J Hum Genet ; 2013 Apr; 19(2): 219-232
Article in English | IMSEAR | ID: sea-149433


BACKGROUND: Human leukocyte antigen (HLA) is comprised of a highly polymorphic set of genes which determines the histocompatibility of organ transplantation. The present study was undertaken to identify HLA class I and class II allele, genotype and haplotype frequencies in renal transplant recipients and donors from West Central India. MATERIALS AND METHODS: HLA typing was carried out using Polymerase Chain Reaction-Sequence Specific Primer in 552 live related and unrelated renal transplant recipients and donors. RESULTS: The most frequent HLA class I and class II alleles and their frequencies in recipients were HLA-AFNx0101 (0.1685) and AFNx0102 (0.1649), HLA-BFNx0135 (0.1322), and HLA-DR beta 1 (DRB 1)FNx0115 (0.2192), whereas in donors, these were HLA-AFNx0102 (0.1848) and AFNx0101 (0.1667), HLA-BFNx0135 (0.1359), and HLA-DRB1FNx0115 (0.2409). The two-locus haplotype statistical analysis revealed HLA-AFNx0102-B61 as the most common haplotype with the frequency of 0.0487 and 0.0510 in recipients and donors, respectively. Further, among the three locus haplotypes HLA-AFNx0133-BFNx0144-DRB1FNx0107 and HLA-AFNx0102-BFNx0161-DRB1FNx0115 were the most common haplotypes with frequencies 0.0362 and 0.0326, respectively in recipients and 0.0236 and 0.0323, respectively in donors. Genotype frequency revealed a high prevalence of genotype HLA-AFNx0102/AFNx0124 in recipients (0.058) compared to donors (0.0109) whereas low prevalence of HLA-AFNx0101/AFNx0102 in recipients (0.0435) than in donors (0.0797). The phylogenetic and principal component analysis of HLA allele and haplotype frequency distribution revealed genetic similarities of various ethnic groups. Further, case control analysis provides preliminary evidence of association of HLA-A genotype (P < 0.05) with renal failure. CONCLUSION: This study will be helpful in suitable donor search besides providing valuable information for population genetics and HLA disease association analysis.

Alleles , Ethnicity/genetics , Genotype , HLA Antigens/classification , HLA Antigens/genetics , Haplotypes , Humans , India , Kidney Transplantation/immunology , Polymorphism, Genetic
Rev. chil. endocrinol. diabetes ; 6(1): 15-22, ene. 2013. ilus, tab
Article in Spanish | LILACS | ID: lil-726584


Type 1 diabetes (T1D) results from autoimmune-mediated destruction of the pancreatic beta cells, a process that is conditioned by multiple genes and environmental factors. The process that destroys the pancreatic b cells in T1D is mediated by T cells and leads to a complex phenotype influenced by multiple factors. It has been more than 30 years since the publication of the first evidence suggesting the involvement of a specific chromosomal region, HLA, in modulating the risk for T1D. HLA locus has been known for decades to contribute strongly with the attributable to genetic risk. In addition to HLA, many proposed candidate loci have been described that are associated with risk of developing the disease, including the insulin gene (INS), PTPN22,CTLA-4, PD-1, IL2-RA and IFIH1 which together do not contribute more than 15 percent of the risk. This review compiled the data on T1D genes and discusses the major genetic impact of these genetic aspects in T1D etiology.

Humans , Diabetes Mellitus, Type 1/genetics , Genetic Markers , DEAD-box RNA Helicases/genetics , /genetics , HLA Antigens/genetics , Genetic Predisposition to Disease , Insulin/genetics , /genetics , /genetics
Rev. méd. Chile ; 140(5): 555-560, mayo 2012. ilus, tab
Article in Spanish | LILACS | ID: lil-648580


Background: Minor histocompatibility antigens (mHAgs) play a critical role in the immune responses associated with allogeneic stem cell transplantation, such as graft versus host disease (GVHD) and graft-versus-tumor (GVT). Aim: To determine the gene frequencies of the mHAgs HA-1, HA-2 and HA-8 in Chilean Blood Bank donors. Material and Methods: Blood from 192 blood donors was analyzed. The presence of haplotype HLA-A*02 was determined by flow cytometry. The frequency of mHAgs was determined by allele specific polymerase chain reaction in genomic DNA. Results: Sixty one participants were carriers of the haplotype HLA-A*02. The relative allele frequency HA-1H was 45%, HA-Ir 55%, HA-2V 80.6%, HA-2M 19.4%, HA-8R 49.8% and HA-8P was 50.2%. Based on mHAgs disparity between HA-1, HA-2 or HA-8, the probability to generate a GVT response in HLA-A*02 individuals was 40%. Conclusions: The mHAgs frequency in Chilean population is under Hardy-Weinberg equilibrium and they are similar to those of other ethnic populations in the world.

Humans , Blood Donors , Graft vs Host Disease , Gene Frequency/genetics , HLA Antigens/genetics , Minor Histocompatibility Antigens/genetics , Chile , Graft vs Host Disease/genetics , Graft vs Host Disease/immunology , Graft vs Tumor Effect/genetics , Histocompatibility Testing , Minor Histocompatibility Antigens/analysis , Minor Histocompatibility Antigens/immunology , Polymerase Chain Reaction , Stem Cell Transplantation , Transplantation, Homologous
An. bras. dermatol ; 87(1): 9-18, Jan.-Feb. 2012. tab
Article in English | LILACS | ID: lil-622446


Skin cancer - melanoma and non melanoma - are common neoplasm with rising incidence over the last decades. It is an important public health problem. Its pathogenesis is not completely understood and the same happens with the genetic factors involved. The genes that encode the HLA are associated with some tumors and they may be responsible for one of the mechanisms that take part in the development of the before mentioned cancers. We have reviewed the literature on the subject of HLA antigens, melanoma and non melanoma skin cancer.

Os cânceres da pele - melanoma e não-melanoma - são neoplasias comuns e com incidência crescente ao longo de décadas. Representam um importante problema de saúde pública. A patogênese destas neoplasias não é completamente compreendida, assim como não o são os fatores genéticos envolvidos. Os genes HLA estão associados a alguns tumores e podem representar um dos mecanismos implicados no desenvolvimento do câncer de pele. Apresenta-se uma revisão atualizada sobre a relação entre antígenos HLA, câncer da pele não-melanoma e melanoma.

Humans , Carcinoma, Basal Cell/genetics , Carcinoma, Squamous Cell/genetics , HLA Antigens/genetics , Melanoma/genetics , Skin Neoplasms/genetics , Carcinoma, Basal Cell/immunology , Carcinoma, Squamous Cell/immunology , Melanoma/immunology , Risk Factors , Skin Neoplasms/immunology
Indian J Hum Genet ; 2012 Jan; 18(1): 109-111
Article in English | IMSEAR | ID: sea-139454


BACKGROUND: Recombination (crossing over) may generate novel haplotypes that can be beneficial to a population against recently introduced pathogens. It may lead to the generation of new alleles. SETTINGS AND DESIGN: A prospective study at a tertiary care centre. AIM: To report two rare cases of crossing over in HLA region. MATERIALS AND METHODS: Tissue-typing was done by sequence specific primers (SSP) for DR locus and by both SSP and serology for Class I which was reconfirmed on fresh samples. RESULTS: In one patient crossing over had taken place in the region of A locus resulting in inheritance of A*01 instead of expected A*11. In second family crossing over had taken place in region of DRB1 locus and the sibling inherited DRB1*08 instead of DRB1*10. CONCLUSIONS: Possibility of recombination must be considered when interpreting implausible tissue-typing results of families worked up for BMT.

Asians/genetics , Family , Histocompatibility Antigens , HLA Antigens/genetics , Family , HLA Antigens/genetics , Histocompatibility Antigens , Humans , India , Major Histocompatibility Complex , Recombination, Genetic
Säo Paulo med. j ; 130(4): 219-224, 2012. ilus, tab
Article in English | LILACS | ID: lil-647946


CONTEXT AND OBJECTIVE: Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings. DESIGN AND SETTING: Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp). METHODS: The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence. RESULTS: Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097). CONCLUSION: This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.

CONTEXTO E OBJETIVO: A doença do enxerto contra o hospedeiro (DECH) é uma das complicações pós-transplante alogênico de células progenitoras hematopoéticas. Este estudo investigou uma associação entre o antígeno leucocitário humano (HLA) e a ocorrência de DECH aguda e crônica, em pacientes que receberam transplantes de irmãos HLA-idênticos. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo no Centro de Hematologia e Hemoterapia da Universidade Estadual de Campinas (Unicamp). MÉTODOS: Os participantes foram 176 pacientes cujo primeiro transplante foi entre 1997 e 2009. A tipagem HLA foi realizada por sorologia e reação em cadeia da polimerase (PCR) com sequência específica de primers. RESULTADOS: A DECH aguda foi associada positivamente com HLA-A10 (P = 0,0007), HLA-A26 (P = 0,002), B55 (P = 0,001), DRB1*15 (P = 0,0211) e DQB1*05 (P = 0,038), enquanto HLA-B16 (P = 0,0333) foi mais frequente em pacientes sem DECH aguda. A DECH crônica foi associada positivamente com HLA-A9 (P = 0,01) e A23 (P = 0,0292) e, negativamente, com HLA-A2 (P = 0,0031) e B53 (P = 0,0116). HLA-B35 (P = 0,0373), B49 (P = 0,0155) e B55 (P = 0,0024) estavam aumentados em pacientes com DECH aguda grau 3 ou maior, em comparação aos outros pacientes. Em pacientes com DECH crônica extensa, HLA-A9 (P = 0,0004), A24 (P = 0,0059) e A26 (P = 0,0411) estavam aumentados em comparação aos outros pacientes, enquanto HLA-A2 estava diminuído (P = 0,0097). CONCLUSÕES: Este estudo sugere que o HLA pode influenciar a ocorrência de DECH aguda e crônica e a sua gravidade. No entanto, um estudo com melhor desenho e com mais pacientes será necessário para confirmar esses resultados.

Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Graft vs Host Disease/immunology , HLA Antigens/immunology , Hematopoietic Stem Cell Transplantation/adverse effects , Acute Disease , Chi-Square Distribution , Chronic Disease , Gene Frequency , Graft vs Host Disease/genetics , HLA Antigens/genetics , Living Donors , Retrospective Studies , Risk Factors , Severity of Illness Index , Transplantation, Homologous/adverse effects , Transplantation, Homologous/immunology
Article in English | IMSEAR | ID: sea-137339


Variability to HIV infection, its progression as well as responsiveness to antiretroviral therapy (ART) is observed among individuals including viraemia controllers or exposed uninfected, rapid versus slow progressors and ART responders compared to non responders. This differential responsiveness/ vulnerability to HIV-1 is governed by multiple host genetic factors that include HLA, cytokines, chemokines, their receptors and others. This review highlights the influence of these genetic factors on HIV/AIDS outcome; however, in India, the information in this area is very limited and most of these genetic studies have been conducted in Caucasian and South African populations. Considering, the population specific differences in the frequencies of protective or susceptibility favouring alleles and their influence on the disease outcome, it is of utmost importance to strengthen ongoing efforts towards defining largely unknown genetic propensity in Indian population, particularly by recruitment of large cohorts of well categorized exposed uninfected individuals, rapid, long term non progressors and elite viraemic controllers. Multi-parametric analysis of these potentially interactive immunogenetic variables in these cohorts may help to define potential targets for diagnostics and therapy in a population specific manner.

Chemokines/genetics , Chemokines/immunology , Cytokines/genetics , Cytokines/immunology , Genetic Predisposition to Disease/ethnology , Genetic Predisposition to Disease/genetics , Genetic Variation , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/genetics , HIV Infections/immunology , HIV Infections/physiopathology , HIV-1/genetics , HIV-1/immunology , HIV-1/pathogenicity , HLA Antigens/genetics , HLA Antigens/immunology , Haplotypes/genetics , Humans , India/epidemiology