RESUMO
The novel HLA-DQB1*06:02:62 allele, first described in an individual from Brazil.
Assuntos
Alelos , Éxons , Cadeias beta de HLA-DQ , Humanos , Cadeias beta de HLA-DQ/genética , Análise de Sequência de DNA/métodos , Teste de Histocompatibilidade/métodos , Brasil , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Códon , Sequência de BasesRESUMO
The novel HLA-DQB1*03:01:61 allele, first described in a potential bone marrow donor from Brazil.
Assuntos
Alelos , Éxons , Cadeias beta de HLA-DQ , Teste de Histocompatibilidade , Humanos , Sequência de Bases , Brasil , Códon , Cadeias beta de HLA-DQ/genética , Análise de Sequência de DNA , Doadores de TecidosRESUMO
HLA-DMB allele frequencies and HLA-DBM-DRB1-DQB1 extended haplotypes were studied for the first time in Amerindians (Cuenca city area, Ecuador). It was found that most common extended haplotypes gathered the most frequent HLA-DRB1 Amerindian alleles. HLA-DMB polymorphism studies may be important to uncover HLA and diseases pathogenesis and also in an extended HLA haplotype frameshift. HLA-DM molecule has a crucial role together with CLIP protein in HLA class II peptide presentation. HLA extended haplotypes including complement and non classical genes alleles are proposed to HLA and disease studies.
Assuntos
Antígenos HLA-D , Antígenos HLA-DQ , Humanos , Alelos , Equador , Frequência do Gene , Haplótipos , Antígenos HLA-D/genética , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genéticaRESUMO
The novel HLA-DQB1*03:491 allele, first described in a potential bone marrow donor from Brazil.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , Humanos , Alelos , Brasil , Transplante de Medula Óssea , Cadeias beta de HLA-DQ/genéticaRESUMO
Characterization of three novel HLA-DQB1 alleles: HLA-DQB1*04:02:01:11, -DQB1*05:01:01:13, and -DQB1*06:03:01:04.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Brasil , Cadeias beta de HLA-DQ/genética , HumanosRESUMO
BACKGROUND: We took advantage of the 2015-2016 Brazilian arbovirus outbreak (Zika [ZIKV]/dengue/chikungunya viruses) associated with neurological complications to type HLA-DRB1/DQA1/DQB1 variants in patients exhibiting neurological complications and in bone marrow donors from the same endemic geographical region. METHODS: DRB1/DQA1/DQB1 loci were typed using sequence-specific oligonucleotides. In silico studies were performed using X-ray resolved dimer constructions. RESULTS: The DQA1*01, DQA1*05, DQB1*02, or DQB1*06 genotypes/haplotypes and DQA1/DQB1 haplotypes that encode the putative DQA1/DQB1 dimers were overrepresented in the whole group of patients and in patients exhibiting peripheral neurological spectrum disorders (PSD) or encephalitis spectrum disorders (ESD). The DRB1*04, DRB1*13, and DQA1*03 allele groups protected against arbovirus neurological manifestation, being underrepresented in whole group of patients and ESD and PSD groups. Genetic and in silico studies revealed that DQA1/DQB1 dimers (1) were primarily associated with susceptibility to arbovirus infections; (2) can bind to a broad range of ZIKV peptides (235 of 1878 peptides, primarily prM and NS2A); and (3) exhibited hydrophilic and highly positively charged grooves when compared to the DRA1/DRB1 cleft. The protective dimer (DRA1/DRB1*04) bound a limited number of ZIKV peptides (40 of 1878 peptides, primarily prM). CONCLUSION: Protective haplotypes may recognize arbovirus peptides more specifically than susceptible haplotypes.
Assuntos
Arbovírus , Alelos , Arbovírus/genética , Frequência do Gene , Predisposição Genética para Doença , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , Síndrome , Zika virus , Infecção por Zika virusRESUMO
Identification of the HLA-DQB1*02:02:13 that differs from HLA-DQB1*02:02:01:01 by a synonymous substitution in exon 2.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Brasil , Cadeias beta de HLA-DQ/genética , HumanosRESUMO
Characterization of three novel HLA-DQB1*05 variants, HLA-DQB1*05:01:01:08, -DQB1*05:02:01:07 and -DQB1*05:03:01:05.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , Alelos , Brasil , Cadeias beta de HLA-DQ , HumanosRESUMO
Identification of the first HLA-DQB1*03:04:01 variant, called HLA-DQB1*03:04:01:02.
Assuntos
Polimorfismo de Nucleotídeo Único , Alelos , Brasil , Cadeias beta de HLA-DQ/genética , HumanosRESUMO
Characterization of two novel HLA-DQB1*06:02:01 variants, HLA-DQB1*06:02:01:05 and -DQB1*06:02:01:06.
Assuntos
Cadeias beta de HLA-DQ , Alelos , Brasil , Cadeias beta de HLA-DQ/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Characterization of two novel HLA-DQB1*05:01:01 variants, HLA-DQB1*05:01:01:06 and DQB1*05:01:01:07.
Assuntos
Cadeias beta de HLA-DQ , Alelos , Brasil , Cadeias beta de HLA-DQ/genética , HumanosRESUMO
BACKGROUND: Accurate pre-transplant prediction of late graft function remains an unmet need in kidney transplantation. The aim of this study was to evaluate HLA genes expression levels in pre-implantation biopsies (PIB) of deceased donor kidneys as markers for long-term graft outcome. METHODS: HLA genes expression analysis was initially performed using microarray data of 53 PIB, previously generated by our laboratory. The validation analysis was performed by real-time PCR in 116 PIB from an independent cohort. RESULTS: The microarray data showed association between high expression levels of HLA class II genes, especially HLA-DQB1 and -DQB2, in kidneys from young (18 to 49-year-old) donors and poor (eGFRâ¯<â¯45â¯mL/min/1.73â¯m2) 1- and 5-year graft function. A subsequent study in an independent cohort, in which only HLA-DQB2 expression was evaluated, validated the association between increased HLA-DQB2 expression in PIB of kidneys from young donors and poor 1-year graft function: expression levels ≥0.0025 relative units conferred an odds ratio of 22.5, with positive and negative predictive values of 71.4% and 90.0%, respectively. CONCLUSION: Heightened expression of HLA-DQB1 and -DQB2 in PIB are promising tools for pre-transplant risk assessment of poor late graft function in transplants with kidneys from 18 to 49-year-old donors.
Assuntos
Rejeição de Enxerto/diagnóstico , Antígenos HLA-DQ/metabolismo , Cadeias beta de HLA-DQ/metabolismo , Transplante de Rim , Rim/metabolismo , Complicações Pós-Operatórias/diagnóstico , Adolescente , Adulto , Biópsia , Feminino , Rejeição de Enxerto/etiologia , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Risco , Regulação para Cima , Adulto JovemRESUMO
The HLA-DRB1*15:01 allele has a demonstrated risk for the development of multiple sclerosis (MS) in most populations around the world. The single nucleotide polymorphism (SNP) rs3129934 is found in linkage disequilibrium with the risk haplotype formed by the HLA-DRB1*15:01 and HLA-DQB1*06:02 alleles, and it is considered a reliable marker of the presence of this haplotype. Native Americans have a null or low prevalence of MS. In this study, we sought to identify the frequency of rs3129934 in the Wixárika ethnic group as well as in Mestizo (mixed race) patients with MS and in controls from western Mexico. Through real-time polymerase chain reaction (PCR) using TaqMan probes, we analyzed the allele and genotype frequencies of rs3129934 in Mestizo individuals with and without MS and in 73 Wixárika subjects from the state of Jalisco, Mexico. The Wixárika subjects were homozygote for the C allele of rs3129934. The allele and genotype frequency in Mestizos with MS was similar to that of other MS populations with Caucasian ancestry. The absence of the T risk allele rs3129934 (associated with the haplotype HLA-DRB1*15:01, HLA-DQ1*06:02) in this sample of Wixárika subjects is consistent with the unreported MS in this Amerindian group, related to absence of such paramount genetic risk factor.
Assuntos
Antígeno HLA-DR2/genética , Esclerose Múltipla/genética , Adulto , Estudos de Casos e Controles , Etnicidade/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Antígeno HLA-DR2/imunologia , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Humanos , Indígenas Norte-Americanos/genética , Desequilíbrio de Ligação , Masculino , México , Esclerose Múltipla/imunologia , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
La investigación en Inmunogenética brinda información acerca de marcadores genéticos asociados con enfermedades autoinmunes, como el Lupus Eritematoso Sistémico (LES), se puede observar entonces ciertos factores de riesgo o protección hacia la enfermedad en una población determinada. OBJETIVO: Determinar la asociación genética entre los polimorfismos del Complejo Principal de Histocompatibilidad (CPH) representados por los loci HLA-DRB1 y HLA-DQB1 con la susceptibilidad a LES. METODOLOGÍA: Se trabajó con 85 pacientes lúpicos y 85 pacientes sin la enfermedad; se obtuvo DNA humano a partir de sangre periférica, se realizó un PCR-SSP de baja y alta resolución para tipificar molecularmente a los loci HLA-DRB1 y HLA-DQB1. Se determinó las frecuencias alélicas, las cuales fueron asociadas con ambas muestras mediante el uso del Odds Ratio, a un nivel de significancia del 5 %. RESULTADOS: Los resultados del PCR-SSP de baja resolución muestran que ningún alelo HLA tiene un rol predisponente, se observó que el alelo HLA-DRB1*04 presenta un rol protector OR=0,49 (p=0,03). Los resultados por PCR-SSP de alta resolución muestran que los alelos HLA-DRB1*03:01 (OR=18,3; p=0,007), DRB1*04:04 (OR=4,2; p=0,009), DRB1*09:01 (OR=18,3; p=0,007), HLA-QB1*03:03 (OR=18,8; p=0,006) y DQB1*02:01 (OR=21,2; p=0,003) son factores de riesgo. Se evidenció que los alelos HLA-DRB1*08:02 (OR=0,42; p=0,003) y HLA-DQB1*04:02 (OR=0,50; p=0,02) son de carácter protector. CONCLUSIONES: Los alelos que representan riesgo de padecer LES en la muestra estudiada son HLA-DRB1*03:01, 04:04, 09:01 y HLA-DQB1*03:03, 02:01. Los alelos que tiene un carácter protector a la enfermedad son HLA-DRB1*08:02 y HLA-DQB1*04:02.
Immunogenetics research provides information on genetic markers associated with autoimmune diseases such as systemic lupus erythematosus (SLE), you can then observe certain risk factors or protection to the disease in a given population. To determine the genetic association between polymorphisms of the Major istocompatibility Complex loci represented by the HLA-DRB1 and HLA-DQB1 with susceptibility to SLE. METHODOLOGY: We worked with 85 lupus patients and 85 patients without the disease; Human DNA was obtained from peripheral blood, PCR-SSP low and high resolution molecularly performed to establish the loci HLA-DRB1 and HLA-DQB1. Allele frequencies, which were associated with both samples using the Odds Ratio at a level of significance of 5% were determined. RESULTS: Results of PCR-SSP low-resolution HLA show that no predisposing allele plays a role, we observed that HLA-DRB1*04 allele has a protective role OR=0.49 (p=0.03). The PCR-SSP results of high resolution show that the HLA-DRB1*03:01 alleles (OR=18.3; p=0.007), DRB1*04:04 (OR=4.2; p=0.009), DRB1*09:01 (OR=18.3; p=0.007), HLA-QB1*03:03 (OR=18.8; p=0.006) and DQB1*02:01 (OR=21.2; p=0.003) are risk factors. We demonstrated that HLA-DRB1*08:02 alleles (OR=0.42; p=0.003) and HLA-QB1*04:02 (OR=0.50; p=0.02) are of a protective nature. CONCLUSIONS: The alleles representing LES risk in the study sample are HLA-DRB1*03:01, *04:04, *09:01 and HLA-DQB1*03:03, *02:01. The alleles having a protective character to the disease are HLADRB1* 08:02 and HLA-DQB1*04:02.
Assuntos
Humanos , Estudos de Associação Genética , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/análise , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
Studies have pointed out that approximately 50-60% of narcolepsy patients may demonstrate higher prevalence of periodical leg movements. However, we highlight that the prevalence studies and the effects of periodical leg movements in patients with narcolepsy are limited and with conflicting results. The objective of this study was that of describing and discussing the prevalence of periodical leg movements in patients with narcolepsy in the outpatient facility of diurnal excessive sleepiness of the Federal University of São Paulo, Brazil. We revised 59 files of patients with the clinical and electrophysiological diagnosis of narcolepsy according to the American Academy of Sleep Medicine. Of these 59 cases of patients with narcolepsy, 12 (20.3%) demonstrated periodical leg movements. Thirty five patients (59.3%) had history of cataplexy and 38 patients (64.4%) had the presence of the allele HLA-DQB1â0602. There was a higher prevalence of periodical leg movements in patients with cataplexy (p<0.0001) and in patients with the presence of the allele HLA-DQB1â0602 (p<0.0001). Our study characterized the higher prevalence of periodical leg movement in patients with narcolepsy, mainly in patients with cataplexy and with the presence of the allele HLA-DQB1â0602.
RESUMO
This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD: 28 patients underwent polysomnographic recordings (PSG) and Multiple Sleep Latency Test (MSLT) were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF) was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N) - Hypocretin-1 higher than 110pg/ml and Lower (L) Hypocretin-1 lower than 110 pg/ml. RESULTS: Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p=0.0002). DISCUSSION: This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level) in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.
Este estudo foi idealizado para avaliar as características clinicas e laboratoriais de uma população de narcolépticos atendidos num centro de referência na cidade de São Paulo (Brasil). MÉTODO: 28 pacientes realizaram polissonografia e teste de múltiplas latências do sono segundo critérios internacionais. O alelo HLADQB1*0602 foi identificado por PCR. A Hipocretina-1 no líquido cefalorradiano (LCR) foi mensurada por radioimunoensaio. Os pacientes foram divididos em 2 grupos conforme o nível de Hipocretina-1. Normal (N) - Hypocretin-1 >110pg/ml e baixa (B) - Hypocretina-1 <110pg/ml. RESULTADOS: Somente 4 pacientes do grupo N tinham cataplexia quando comparados com 14 pacientes do grupo B (p=0,0002). DISCUSSÃO: Estes resultados foram comparáveis com outros autores, confirmando a utilidade do uso de biomarcadores específicos (HLA-DQB1*0602 e nível da hipocretina-1 no LCR) em narcolepsia com cataplexia. Porém, o alelo HLADQB1*0602 e a dosagem da Hipocretina-1 são insuficientes para o diagnóstico da narcolepsia sem cataplexia.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos HLA-DQ/genética , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Glicoproteínas de Membrana/genética , Narcolepsia/diagnóstico , Neuropeptídeos/líquido cefalorraquidiano , Alelos , Biomarcadores , Cataplexia/líquido cefalorraquidiano , Cataplexia/diagnóstico , Cataplexia/genética , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/genética , Reação em Cadeia da Polimerase , Polissonografia , RadioimunoensaioRESUMO
OBJECTIVE: Narcolepsy (with and without cataplexy) and idiopathic hypersomnia, are disorders with common features but with different HLA-DQB1*0602 allele prevalence. The present study describes the prevalence of HLA-DQB1*0602 allele in narcoleptics with and without cataplexy and in patients with idiopathic hypersomnia. METHOD: Subjects comprised 68 patients who were diagnosed for narcolepsy or idiopathic hypersomnia and 23 healthy controls according to the International Classification of Sleep Disorders-2. Subjects comprised 43 patients with narcolepsy and cataplexy, 11 patients with narcolepsy but without cataplexy, 14 patients with idiopathic hypersomnia and 23 healthy controls. Genotyping of HLA-DQB1*0602 allele was performed for all subjects. RESULTS: The prevalence of the HLA-DQB1*0602 allele was increased in idiopathic hypersomnia and in narcoleptic patients with and without cataplexy when compared to healthy subjects (p = 0.04; p = 0.03 and p < 0.0001, respectively). CONCLUSIONS: This finding is in accordance with those of previous studies. The gold standard exam of narcolepsy with cataplexy is Hypocretin-1 dosage, but in patients without cataplexy and idiopathic hypersomnia, there are no specific diagnostic lab findings. The presence of the HLA-DQB1* 0602 allele may be important for the differential diagnosis of situations that resemble those sleep disorders such as secondary changes in sleep structure due to drugs' consumption.
OBJETIVO: Narcolepsia (com e sem cataplexia) e hipersonolência idiopática são transtornos com características clínicas comuns, mas com prevalências do alelo HLA-DQB1*0602 diferentes. Este estudo descreve a prevalência do alelo HLA-DQB1*0602 em pacientes narcolépticos com e sem cataplexia e em pacientes com hipersonolência idiopática. MÉTODO: A amostra consistiu de 68 pacientes com diagnóstico de narcolepsia ou hipersonolência idiopática e 23 controles saudáveis segundo o International Classification of Sleep Disorders-2. A amostra foi composta de 43 pacientes com narcolepsia e cataplexia, 11 pacientes com narcolepsia e sem cataplexia, 14 pacientes com hipersonolência idiopática e 23 controles saudáveis. A análise da presença do alelo HLA-DQ*0602 foi realizada em todos os sujeitos. RESULTADOS: A prevalência do alelo HLA-DQB1*0602 foi maior nos grupos de pacientes com hipersonolência idiopática e em pacientes narcolépticos com e sem cataplexia quando comparada com a dos sujeitos saudáveis (p = 0,04; p = 0,03 e p < 0,0001, respectivamente). CONCLUSÕES: Os resultados são compatíveis com o de estudos anteriores. O exame padrão-ouro para a confirmação da narcolepsia em pacientes com cataplexia é a dosagem de hipocretina, mas em pacientes sem cataplexia e hipersonolência idiopática não há testes laboratoriais específicos para o diagnóstico. A presença do alelo HLA-DQB1*0602 pode ser importante no diagnóstico diferencial de situações semelhantes a esses distúrbios do sono, como alterações secundárias na estrutura do sono causadas por consumo de drogas.
Assuntos
Adolescente , Adulto , Idoso , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Alelos , Antígenos HLA-DQ/genética , Hipersonia Idiopática/diagnóstico , Hipersonia Idiopática/genética , Glicoproteínas de Membrana/genética , Narcolepsia/diagnóstico , Narcolepsia/genética , Brasil , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Diagnóstico Diferencial , Estatísticas não Paramétricas , Adulto JovemRESUMO
BACKGROUND: Studies have shown a high prevalence of migraine among narcoleptic patients. HLA-DQB1*0602 and HLA DRB1 alleles are closely associated with narcolepsy. An increase in the HLA-DRB1 allele frequency in patients with visual aura has raised greater awareness of the genetic background in migraine. PURPOSE: Since the regions DR and DQ of the HLA are in tightly linkage desiquilibrium we hypothesize that HLA-DQB1*0602 might be associated to the pathophysiology of migraine. METHOD: We analyzed the presence of HLA DQB1*0602 allele in 50 healthy subjects with no history of migraine, 53 patients with migraine without aura and 52 patients with migraine with aura. RESULTS: There was no difference in the frequency of HLA DQB1*0602 allele when control subjects and all patients were compared. We failed to note any difference in frequencies when comparing migraine patients with and without aura. CONCLUSION: Further studies with different patient populations, with other hypothalamic markers (melatonin, hypocretin) in migraine patients may shed light on to its pathophysiology.
CONTEXTO: Estudos têm demonstrado o aumento da prevalência de enxaqueca em pacientes com narcolepsia, um distúrbio de sono associado a um gene do sistema HLA, o alelo HLA-DQB1*0602. As regiões DQ e DR do HLA estão em alto desequilíbrio de ligação e já foi descrito um aumento da freqüência do alelo HLA DRB1 em pacientes com enxaqueca com aura visual, o que fortalece uma hipótese de herança genética para a enxaqueca. OBJETIVO: Nossa hipótese é que o alelo HLA-DQB1*0602 pode estar relacionado com a fisiopatologia da enxaqueca destes pacientes. MÉTODO: Nós analisamos a presença do alelo HLA-DQB1*0602 em 50 voluntários sadios sem história de enxaqueca, 53 pacientes com enxaqueca sem aura e 52 pacientes com aura. RESULTADOS: Não houve diferença entre os controles sadios e os pacientes com enxaqueca. Não houve diferença entre os pacientes com enxaqueca com e sem aura. CONCLUSÃO: Futuros estudos com diferentes populações, com outros marcadores (melatonina e hipocretina) em pacientes com enxaqueca devem ser realizados para melhor esclarecimento de fisiopatologia.