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2.
Egypt J Immunol ; 26(1): 113-120, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31333001

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease associated with multiple genetics and environmental factors. The aim of the study is to determine the frequency of HLA-B*08 and HLA-B*39 and its linkage disequilibrium with common risk haplotypes DR3-DQA1*05-DQB1*02, and DR4-DQA1-03-DQB1*0302 among T1D Egyptian infants. And assess different environmental factors as early exposure to cow's milk, exclusive breast feeding, mode of delivery and low birth weight. Sixty eight diabetic infants and 120 healthy controls were studied. HLA-DQB1, and DQA1 alleles were identified using homogeneous PCR and oligonucleotide hybridization assays. HLA-B*08 and HLA-B*39 genes were identified using multiplex PCR. The results showed that early exposure to cow's milk before 6 months carry a significant risk for T1D (16% in patients versus 6.6%in control group, P value=0.03). HLA-B*08 frequency was significantly higher among T1D infants than in control group (14.5% in diabetic infants versus 5%in control group, P value=0.024). DR3-DQA1*05-DQB1*02, and DR4-DQA1-03-DQB1*0302 were significantly higher in diabetic infants than controls (P value < 0.001 and 0.004 respectively). HLA-B*08 gene was found in (15.5%) of DR3-DQA1*05-DQB1*02 positive cases while in control group it was found in (13.5%) (P value=0.8). In conclusion, HLA-B*08 gene carry a risk for T1D in Egyptian infants, while DR3-DQA1*05-DQB1*02 haplotype lacks linkage disequilibrium with HLA-B*08 among T1D infants. Further studies are needed to determine which HLA-B gene is strongly linked to DR3-DQA1*05-DQB1*02 haplotype in T1D infants other than HLA-B*08 and HLA-B*18.


Assuntos
Diabetes Mellitus Tipo 1/genética , Antígenos HLA-B/genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Antígeno HLA-DR3/genética , Desequilíbrio de Ligação , Leite , Alelos , Animais , Estudos de Casos e Controles , Bovinos , Egito , Predisposição Genética para Doença , Haplótipos , Humanos , Lactente , Fatores de Risco
3.
Immunol Med ; 42(1): 22-28, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31169082

RESUMO

Bullous pemphigoid (BP) is an organ-specific autoantibody-mediated autoimmune blistering skin disorder that tends to affect the elderly. Tense blister formation associated with itchy urticarial erythema is clinically observed in BP, and subepidermal blister formation with eosinophilic infiltration is a histopathological characteristic. BP autoantibodies target two hemidesmosomal components in basal keratinocytes: BP180 and BP230. Anti-BP180 autoantibodies play major roles in blister formation. Although the autoantibody-mediated pathomechanism of blister formation has been extensively studied, little is known about how and why immune tolerance to BP180 may be broken in certain elderly individuals. Recently, BP has been increasingly reported in diabetes mellites (DM) patients receiving dipeptidyl peptidase-IV inhibitors (DPP4is), which are widely used anti-DM drugs. Pharmacovigilance and cohort studies have revealed that DPP4is, especially vildagliptin, teneligliptin, and linagliptin, are a potential risk factor for BP onset. Interestingly, it has been revealed that Japanese DPP4i-BP tends to show a non-inflammatory phenotype, with less erythema than normal BP, and that DPP4i-BP autoantibodies target distinct epitopes on BP180. In addition, human leukocyte antigen-DQB1*03:01 was identified as the major haplotype in Japanese DPP4i-BP. This review summarizes the latest understanding of the pathogenesis of BP, with a special focus on the recently recognized DPP4i-BP.


Assuntos
Autoimunidade , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hipoglicemiantes/administração & dosagem , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/imunologia , Grupo com Ancestrais do Continente Asiático , Autoanticorpos , Autoantígenos/imunologia , Epitopos , Cadeias beta de HLA-DQ/genética , Haplótipos , Humanos , Tolerância Imunológica/imunologia , Linagliptina/efeitos adversos , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/genética , Pirazóis/efeitos adversos , Fatores de Risco , Tiazolidinas/efeitos adversos , Vildagliptina/efeitos adversos
5.
Mol Carcinog ; 58(7): 1324-1333, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31001878

RESUMO

Genetic factors play important roles in colorectal carcinogenesis. This study was aimed to evaluate the effects of gene expression-related copy number variations (CNVs) on the risk of colorectal cancer in Chinese. Expression Quantitative Trait Locus (eQTL) mapping was conducted to explore the most regulatable gene expressions by CNVs among the whole genome based on publicly available data. Then a case-control study was performed to evaluate the associations between copy numbers of the most regulatable genes and colorectal cancer. The influence of the target CNVs on the expression of corresponding gene and protein was verified in colorectal tissue, and the biological effects of these CNVs on cell-cycle arrest and apoptosis of colon cancer cell lines were further detected. The eQTL revealed the most significant association between CNV of HM3_CNP_342 and gene expressions of human leukocyte antigen (HLA)-DQA1 and HLA-DQB1 among the whole genome. The later case-control study found that amplified HLA-DQB1 was inversely associated with colorectal cancer risk (odds ratio = 0.73; 95% confidence interval: 0.58-0.93), especially among those with a family history of cancer. The positive association between amplified HLA-DQB1 and upregulation of gene and protein was validated in colorectal tissue. In addition, overexpression of HLA-DQB1 in dendritic cells promoted cell-cycle arrest and apoptosis of cocultured SW480 and HCT116 cell lines, and vice versa. Our study suggests that the amplified copy number of HLA-DQB1 is associated with lower risk of colorectal cancer and able to induce the apoptosis of colon cancer cells, which implies the potential of HLA class II in cancer predisposition and immunotherapy.


Assuntos
Neoplasias do Colo/genética , Variações do Número de Cópias de DNA/genética , Predisposição Genética para Doença/genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Apoptose/genética , Estudos de Casos e Controles , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , China , Feminino , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Células HCT116 , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética
6.
J Neurol ; 266(4): 982-989, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30741378

RESUMO

BACKGROUND: The relative prevalence of myasthenia gravis (MG) subtypes is changing, and their differential features and association with HLA class II alleles are not completely understood. METHODS: Age at onset, presence/absence of autoantibodies (Ab) and thymoma were retrospectively considered in 230 adult Italian patients. Clinical severity, assessed by MGFA scale, and the highest Ab titer were recorded. Furthermore, we performed low/high resolution typing of HLA-DRB1 and HLA-DQB1 alleles to detect associations of these loci with MG subtypes. RESULTS: There were two peaks of incidence: under 41 years of age, with female preponderance, and over 60 years, with higher male prevalence. The former group decreased and the latter increased significantly when comparing onset period 2008-2015 to 2000-2007. Thymomatous (TMG) patients showed a higher prevalence of severe phenotype and significantly higher anti-AChR Ab titer than non-thymomatous (NTMG) patients. Among the latter, those with onset after 60 years of age (LO-NTMG) displayed significantly higher Ab titers but lower MGFA grade compared to early-onset patients (< 41 years; EO-NTMG). Significant associations were found between HLA DQB1*05:01 and TMG patients and between DQB1*05:02 and DRB1*16 alleles and LO-NTMG with anti-AChR Ab. CONCLUSIONS: Two distinct cutoffs (< 41 and > 60 years) conveniently define EO-NTMG and LO-NTMG, with different characteristics. LO-NTMG is the most frequent disease subtype, with an increasing incidence. TMG patients reach higher clinical severity and higher antibody titers than NTMG patients. Moreover, TMG and LO-NTMG with anti-AChR Ab differ in their HLA-DQ association, providing further evidence that these two forms may have different etiologic mechanisms.


Assuntos
Miastenia Gravis/epidemiologia , Timoma/epidemiologia , Neoplasias do Timo/epidemiologia , Adulto , Idade de Início , Autoanticorpos/sangue , Feminino , Predisposição Genética para Doença , Cadeias beta de HLA-DQ/genética , Humanos , Fenômenos Imunogenéticos , Incidência , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/genética , Miastenia Gravis/imunologia , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Timoma/genética , Timoma/imunologia , Neoplasias do Timo/genética , Neoplasias do Timo/imunologia
7.
Nat Commun ; 10(1): 837, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30783092

RESUMO

Narcolepsy Type 1 (NT1) is a neurological sleep disorder, characterized by the loss of hypocretin/orexin signaling in the brain. Genetic, epidemiological and experimental data support the hypothesis that NT1 is a T-cell-mediated autoimmune disease targeting the hypocretin producing neurons. While autoreactive CD4+ T cells have been detected in patients, CD8+ T cells have only been examined to a minor extent. Here we detect CD8+ T cells specific toward narcolepsy-relevant peptides presented primarily by NT1-associated HLA types in the blood of 20 patients with NT1 as well as in 52 healthy controls, using peptide-MHC-I multimers labeled with DNA barcodes. In healthy controls carrying the disease-predisposing HLA-DQB1*06:02 allele, the frequency of autoreactive CD8+ T cells was lower as compared with both NT1 patients and HLA-DQB1*06:02-negative healthy individuals. These findings suggest that a certain level of CD8+ T-cell reactivity combined with HLA-DQB1*06:02 expression is important for NT1 development.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Cadeias beta de HLA-DQ/genética , Narcolepsia/imunologia , Orexinas/imunologia , Peptídeos/imunologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/genética , Neurônios/metabolismo , Orexinas/metabolismo
8.
PLoS One ; 14(2): e0212329, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30763397

RESUMO

BACKGROUND AND AIMS: Experimental data suggest that the HLA-DQ2 gene dose has a strong quantitative effect on clinical outcomes and severity of celiac disease (CD). We aimed to conduct a meta-analysis with systematic review to investigate the association between HLA-DQB1*02 gene doses and the characteristics of CD. METHODS: We searched seven medical databases for studies discussing HLA-DQB1 gene dose in CD and various disease characteristics, such as clinical presentation, histology, age at diagnosis, and comorbidities. Odds ratios (OR, for categorical variables) and weighted mean differences (for age) were calculated to compare patients with a double dose of HLA-DQB1*02 versus those with single and zero doses. Heterogeneity was tested with I2-statistics and explored by study subgroups (children and adults). RESULTS: Twenty-four publications were eligible for meta-analysis. Classical CD was more frequent with a double versus single dose of the HLA-DQB1*02 allele (OR = 1.758, 95%CI: 1.148-2.692, I2 = 0.0%). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95%CI: 1.189-3.646, I2 = 0.0% and OR = 3.139, 95%CI: 1.142-8.630, I2 = 0.0% for the comparisons of double versus single and double versus zero dose, respectively). Atrophic histology was more prevalent with a double versus zero dose (OR = 2.626, CI: 1.060-6.505, I2 = 21.3%). We observed no gene dose effect regarding diarrhea, age at diagnosis, the severity of villous atrophy, and the association with type 1 diabetes mellitus. CONCLUSION: A double dose of HLA-DQB1*02 gene seems to predispose patients to developing classical CD and villous atrophy. Risk stratification by HLA-DQB1*02 gene dose requires further clarification due to the limited available evidence.


Assuntos
Doença Celíaca/patologia , Cadeias beta de HLA-DQ/genética , Alelos , Doença Celíaca/diagnóstico , Doença Celíaca/genética , Bases de Dados Factuais , Dosagem de Genes , Humanos , Razão de Chances , Índice de Gravidade de Doença
9.
ESC Heart Fail ; 6(2): 388-395, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30672659

RESUMO

AIMS: Cell therapy can be used to repair functionally impaired organs and tissues in humans. Although autologous cells have an immunological advantage, it is difficult to obtain high cell numbers for therapy. Well-characterized banks of cells with human leukocyte antigens (HLA) that are representative of a given population are thus needed. The present study investigates the HLA allele and haplotype frequencies in a cohort of heart failure (HF) patients. METHODS AND RESULTS: We carried out the HLA typing and the allele and haplotype frequency analysis in 247 ambulatory HF patients. We determined HLA class I (A, B, and C) and class II (DRB1 and DQB1) using next-generation sequencing technology. The allele frequencies were obtained using Python for Population Genomics (PyPop) software, and HLA haplotypes were estimated using HaploStats. A total of 30 HLA-A, 56 HLA-B, 23 HLA-C, 36 HLA-DRB1, and 15 HLA-DQB1 distinct alleles were identified within the studied cohort. The genotype frequencies of all five HLA loci were in Hardy-Weinberg equilibrium. We detected differences in HLA allele frequencies among patients when the etiological cause of HF was considered. There were a total of 494 five-loci haplotypes, five of which were present six or more times. Moreover, the most common estimated HLA haplotype was HLA-A*01:01, HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, and HLA-DQB1*02:01 (6.07% haplotype frequency per patient). Remarkably, the 11 most frequent haplotypes would cover 31.17% of the patients of the cohort in need of allogeneic cell therapy. CONCLUSIONS: Our findings could be useful for improving allogeneic cell administration outcomes without concomitant immunosuppression.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Insuficiência Cardíaca/genética , Idoso , Alelos , Feminino , Frequência do Gene , Genótipo , Antígenos HLA-A/metabolismo , Antígenos HLA-B/metabolismo , Antígenos HLA-C/metabolismo , Cadeias beta de HLA-DQ/metabolismo , Cadeias HLA-DRB1/metabolismo , Haplótipos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/terapia , Humanos , Masculino
10.
J Clin Neurosci ; 59: 179-184, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30595166

RESUMO

To compare HLA typing between juvenile- and adult-onset myasthenia gravis (MG), we enrolled 101 children (age ≤12 years) and 168 adults (age ≥20 years) with MG. We excluded patients with histories of thymoma, thyroid disease, or other autoimmune disease. We selected 41 seronegative juvenile-onset patients with ocular symptoms only, and 41 seropositive adult-onset patients with generalized symptoms. We used next-generation sequencing for typing and analysis of HLA genes (Loci: A, B, C, DPA1, DPB1, DQA1, DQB1 and DRB1). Haplotypes HLA-A∗02:07:01-B∗46:01:01-C∗01:02:01-DQA1∗01:01:01-DQB1∗03:03:02-DRB1∗09:01:02, HLA-A∗11:01:01, HLA-A∗24:02:01, and HLA-DPA1∗02:02:02 were found to be related to juvenile-onset MG and HLA-A∗01:01:01, HLA-A∗02:03:01, HLA-C∗03:04:01, and HLA-DQB1∗06:02:01 to adult-onset MG. Therefore, our findings suggested that HLA typing might determine the heterogeneity between AChR-Ab negative juvenile-onset and AChR-Ab positive adult-onset Chinese MG patients.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Teste de Histocompatibilidade/métodos , Miastenia Gravis/genética , Adulto , Criança , Feminino , Cadeias alfa de HLA-DP/sangue , Cadeias alfa de HLA-DP/genética , Cadeias beta de HLA-DQ/sangue , Cadeias beta de HLA-DQ/genética , Haplótipos/genética , Sequenciamento de Nucleotídeos em Larga Escala/tendências , Teste de Histocompatibilidade/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Miastenia Gravis/diagnóstico , Adulto Jovem
11.
Diabetes Care ; 42(3): 406-415, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30659077

RESUMO

OBJECTIVE: Genetic risk scores (GRS) have been developed that differentiate individuals with type 1 diabetes from those with other forms of diabetes and are starting to be used for population screening; however, most studies were conducted in European-ancestry populations. This study identifies novel genetic variants associated with type 1 diabetes risk in African-ancestry participants and develops an African-specific GRS. RESEARCH DESIGN AND METHODS: We generated single nucleotide polymorphism (SNP) data with the ImmunoChip on 1,021 African-ancestry participants with type 1 diabetes and 2,928 control participants. HLA class I and class II alleles were imputed using SNP2HLA. Logistic regression models were used to identify genome-wide significant (P < 5.0 × 10-8) SNPs associated with type 1 diabetes in the African-ancestry samples and validate SNPs associated with risk in known European-ancestry loci (P < 2.79 × 10-5). RESULTS: African-specific (HLA-DQA1*03:01-HLA-DQB1*02:01) and known European-ancestry HLA haplotypes (HLA-DRB1*03:01-HLA-DQA1*05:01-HLA-DQB1*02:01, HLA-DRB1*04:01-HLA-DQA1*03:01-HLA-DQB1*03:02) were significantly associated with type 1 diabetes risk. Among European-ancestry defined non-HLA risk loci, six risk loci were significantly associated with type 1 diabetes in subjects of African ancestry. An African-specific GRS provided strong prediction of type 1 diabetes risk (area under the curve 0.871), performing significantly better than a European-based GRS and two polygenic risk scores in independent discovery and validation cohorts. CONCLUSIONS: Genetic risk of type 1 diabetes includes ancestry-specific, disease-associated variants. The GRS developed here provides improved prediction of type 1 diabetes in African-ancestry subjects and a means to identify groups of individuals who would benefit from immune monitoring for early detection of islet autoimmunity.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Diabetes Mellitus Tipo 1/etnologia , Diabetes Mellitus Tipo 1/genética , Testes Genéticos , Antígenos HLA-D/genética , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Alelos , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Testes Genéticos/normas , Estudo de Associação Genômica Ampla , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Projetos de Pesquisa , Fatores de Risco
12.
Hum Immunol ; 80(4): 215-217, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30685398

RESUMO

HLA-DRB1, -DQB1 and -DPB1 allele frequencies and estimated haplotype frequencies from 496 unrelated healthy Mongol subjects who living in Inner Mongolia Autonomous Region of China has been reported. HLA genes were genotyped using high-resolution sequence-based typing method. Chinese-Mongolian belongs to northern group of East Asians, but with its specific HLA-DRB1, DPB1 and DQB1 alleles and haplotypes characteristic.


Assuntos
Genótipo , Cadeias beta de HLA-DP/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Alelos , Grupo com Ancestrais do Continente Asiático , China , Grupos Étnicos , Frequência do Gene , Teste de Histocompatibilidade , Humanos , Mongólia , Polimorfismo Genético
13.
Int J Immunogenet ; 46(1): 7-16, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30592160

RESUMO

The distributions of HLA allele and haplotype are variable in different ethnic populations and the data for some populations have been published. However, the data on HLA-C and HLA-DQB1 loci and the haplotype of HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci at a high-resolution level are limited in Zhejiang Han population, China. In this study, the frequencies of the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci and haplotypes were analysed among 3,548 volunteers from the Zhejiang Han population using polymerase chain reaction sequencing-based typing method. Totals of 51 HLA-A, 97 HLA-B, 45 HLA-C, 53 HLA-DRB1 and 27 HLA-DQB1 alleles were observed. The top three frequent alleles of HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci were A*11:01 (23.83%), A*24:02 (17.16%), A*02:01 (11.36%); B*40:01 (14.08%), B*46:01 (12.20%), B*58:01 (8.50%); C*07:02 (18.25%), C*01:02:01G (18.15%), C*03:04 (9.88%); DRB1*09:01 (17.52%), DRB1*12:02 (10.57%), DRB1*15:01 (9.70%); DQB1*03:01 (22.63%), DQB1*03:03 (18.26%) and DQB1*06:01 (10.88%), respectively. A total of 141 HLA-A-C-B-DRB1-DQB1 haplotypes with a frequency of ≥0.1% were found and the haplotypes with frequency greater than 3% were A*02:07-C*01:02:01G-B*46:01-DRB1*09:01-DQB1*03:03 (4.20%), A*33:03-C*03:02-B*58:01-DRB1*03:01-DQB1*02:01 (4.15%), A*30:01-C*06:02-B*13:02-DRB1*07:01-DQB1*02:02 (3.20%). The likelihood ratios test for the linkage disequilibrium of two loci haplotypes was revealed that the majority of the pairwise associations were statistically significant. The data presented in this study will be useful for searching unrelated HLA-matched donor, planning donor registry and for anthropology studies in China.


Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Alelos , China , Feminino , Frequência do Gene , Genética Populacional , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Grupos Populacionais/genética
14.
J Transl Med ; 16(1): 362, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30563535

RESUMO

BACKGROUND: Infection with the hepatitis B virus (HBV) is an independent risk factor for liver cirrhosis and hepatocellular carcinoma, polymorphisms in HLA-DQB1 play an important role in HBV infections. METHODS: This study examined the relationships between HLA-DQB1 alleles and HBV infection susceptibility among 256 HBV carriers and 433 healthy controls. Venous blood samples were subjected to DQB1 high-resolution typing and testing for interferon-gamma, interleukin-4 (IL-4), interleukin-10, and DQB1 mRNA expression. A meta-analysis was also performed using relevant case-control studies that evaluated the associations of HLA-DQB1 alleles with HBV infection and clearance. RESULTS: We found that HLA-DQB1*06:03 protected against HBV infection. Levels of IFN-γ and IL-4 were significantly elevated in HBV cases with HLA-DQB1*06:05 (vs. HLA-DQB1*05:03), and the HBV group had higher DQB1 mRNA expression than the healthy control group with HLA-DQB1*05:03 and HLA-DQB1*06:02. The meta-analysis revealed that HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01 were risk factors for HBV infection susceptibility, while HLA-DQB1*05:01, HLA-DQB1*06:03, and HLA-DQB1*06:04 protected against HBV infection. Spontaneous HBV clearance was associated withHLA-DQB1*06:04, while chronic HBV infection was associated with HLA-DQB1*02:01 and HLA-DQB1*05:02. CONCLUSION: DBQ1 typing can be used to identify patients who have elevated risks of HBV infection (i.e., patients with HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01) or elevated risks of chronic HBV infection (i.e., patients with HLA-DQB1*02:01 and HLA-DQB1*05:02).


Assuntos
Cadeias beta de HLA-DQ/genética , Vírus da Hepatite B/fisiologia , Hepatite B/virologia , Polimorfismo Genético , Alelos , Citocinas/sangue , Predisposição Genética para Doença , Cadeias beta de HLA-DQ/metabolismo , Hepatite B/genética , Metanálise como Assunto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
Gene ; 674: 93-97, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29958949

RESUMO

This study included 161 patients: 92 patients had type 1 diabetes (T1D) while 69 patients had a combination of T1D and autoimmune thyroiditis, the so-called autoimmune polyglandular syndrome type 3 variant (APS3v). Those patients, as well as 93 controls, were typed for HLA-DRB1 and -DQB1 genes to assess their possible contribution to the development/protection of T1D with/without autoimmune thyroiditis. Both HLA-DRB1*04 and -DRB1*03 frequencies were significantly higher among T1D and APS3v patients than in controls. The frequencies of HLA-DRB1*11 and -DRB1*15 were lower among T1D patients, while HLA-DRB1*07 and -DRB1*11 occurred significantly less frequently among APS3v patients in comparison to controls. HLA-DQB1*03:01 and -DQB1*03:02 were associated with a higher risk of developing T1D and APS3v; HLA-DQB1*02 was significantly more present among APS3v patients while HLA-DQB1*03:03 was observed with a significantly lower frequency only among T1D patients. HLA-DRB1*03~DQB1*02 and HLA-DRB1*04~DQB1*03:02 were associated with both diseases. The higher frequency of HLA-DRB1*03/DRB1*03 among APS3v patients was the only significant difference in genotype frequency when compared to T1D patients, while high risk (HLA-DRB1*03/DRB1*04) and medium risk genotypes for T1D (HLA-DRB1*04/DRB1*04) occurred with similar frequencies in both patient groups. Although some of the results point toward shared genetic susceptibility of T1D and APS3v, observed differences in both susceptible/protective HLA profiles indicate the necessity of further studies in order to elucidate the pathogenesis of these diseases.


Assuntos
Diabetes Mellitus Tipo 1/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Poliendocrinopatias Autoimunes/genética , Polimorfismo Genético , Adolescente , Adulto , Criança , Pré-Escolar , Croácia , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Lactente , Masculino , Poliendocrinopatias Autoimunes/complicações , Adulto Jovem
16.
Transplant Proc ; 50(6): 1605-1615, 2018 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29937294

RESUMO

INTRODUCTION: Thanks to new generation sequencing (NGS) and expansion of HLA typing with additional loci, it will be possible to increase the effectiveness of graft survival and to avoid complications related to the immune system. New pharmacogenetic factors are still being researched to develop better immunosuppressive treatment. MATERIAL AND METHODS: The incidence of polymorphic HLA loci variants was established, based on a high-resolution NGS method in kidney graft recipients. Furthermore, haplotypic analysis between examined loci was conducted to type additional loci that may influence the transplantation result. A total of 120 kidney recipients were enrolled in the study. A commercial DNA extraction kit in Tubes (QIAamp DNA Blood Mini Kit Qiagen, Germany) was used to isolate DNA from the blood. Sequencing library preparation was done with TruSight HLA set. The Conexio computer program was used to analyse the results of HLA typing. RESULTS: The patients with alleles A*02:01:01, B*44:02:01, C*03:03:01, C*01:02:01, C*05:01:01, C*07:02:01, DQB1*03:03:02, DQB1*06:04:01, or with haplotypic variation A*25:01:01-B*18:01:01- C*15:01:01 were taking the highest doses of cyclosporine (CsA), in contrast to patients with allele B*18:01:01, DQB1*06:02:01, DQB1*02:02:01, or haplotypic variation A*02:01:01- B*44:02:01-C*01:01:01, who were taking the lowest doses. The highest dose of tacrolimus (TAC) was administered to patients with alleles A*68:01:02, A*29:01:01, B*07:02:01, B*35:02:01, B*38:01:01, DRB1*12:01:01, DQB1*05:03:01, or haplotypic variations A*02:01:01-B*57:01:01-C*07:01:01, A*03:01:01-B*07:02:01-C*13:01:01, A*29:02:01-B*44:03:01- C*07:01:01, and A*01:01:01-B*08:01:01-C*03:01:01. Additionally, it was established that HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DPA1, and HLA-DQA1 show very slight polymorphism, which suggests that there is no need for their typing for transplantation purposes. Moreover, loci HLA-C, HLA-DQB1, and HLA-DPB1, which are not routinely examined in recipient-donor matching, show genetic variability that may increase the risk of transplant rejection or shortened graft life. CONCLUSIONS: Expanding the qualification procedure to include allele genotyping could allow clinicians to establish immunosuppressive treatment schemes that would be optimally suited for recipients' phenotype.


Assuntos
Sobrevivência de Enxerto/genética , Teste de Histocompatibilidade/métodos , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Ciclosporina/administração & dosagem , Feminino , Loci Gênicos , Técnicas de Genotipagem/métodos , Sobrevivência de Enxerto/imunologia , Antígenos HLA-C/genética , Cadeias alfa de HLA-DP/genética , Cadeias beta de HLA-DP/genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Fenótipo , Polimorfismo Genético , Tacrolimo/administração & dosagem , Resultado do Tratamento , Adulto Jovem
17.
J Immunol Res ; 2018: 2031571, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850621

RESUMO

Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies.


Assuntos
Transplante de Medula Óssea , Genótipo , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Sistema de Registros , Grupo com Ancestrais do Continente Africano , Alelos , Frequência do Gene , Haplótipos , Humanos , Masculino , Software , África do Sul , Doadores de Tecidos , Voluntários
18.
BMC Gastroenterol ; 18(1): 70, 2018 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-29793442

RESUMO

BACKGROUND: Celiac disease (CD) is a common autoimmune disease in Syria which manifesting with inflammation of the small intestine and with various extra intestinal symptoms. The disease is associated with human HLA-DQ genes encoding HLA-DQ2 and DQ8 proteins. METHODS: In this study, 49 children patients of CD and 58 healthy control samples were genotyped for HLA-DQ genes using SSP-PCR technique. Relative risks for different genotypes were also evaluated. RESULTS: The DQB1*0201 allele was the most common in the patients (77.6%) followed by DQB1*0302 allele (10.2%). The highest HLA-DQB risk for CD development was found in patients carriers a DQ2.5/DQ8 genotype (1/10), followed by the patients carriers DQ2.5/DQ2.5 (1/12). CONCLUSION: The significant differences in the frequency of HLA-DQ2 and HLA-DQ8 in Syrian patients in compared with controls and relative risks predicted demonstrated the importance role of these alleles in the development of CD in Syrian children patients.


Assuntos
Doença Celíaca/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Cadeias beta de HLA-DQ/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Criança , Pré-Escolar , Antígenos HLA-DQ/genética , Humanos , Lactente , Prevalência , Fatores de Risco , Síria/epidemiologia , Adulto Jovem
19.
Hum Immunol ; 79(8): 594-601, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29800590

RESUMO

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 (eGFR < 45 mL/min/1.73 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 Jovem
20.
J Clin Lab Anal ; 32(7): e22443, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29667729

RESUMO

BACKGROUND: Gastric cancer (GC) is a disease associated with a higher incidence and mortality, and some host genetic polymorphisms have been reported as potential factors contributing to the development of GC. In view of this, the study was conducted to investigate the effects of HLA-DQB1 gene polymorphisms and perioperative blood transfusion on prognosis of patients with gastric cancer (GC). METHODS: A total of 142 patients with GC (case group) and 150 healthy controls (control group) were enrolled. Relationship between HLA-DQB1 gene polymorphisms, perioperative blood transfusion, and clinical pathological parameters of patients with GC after operation was analyzed. Kaplan-Meier curve was applied for analyzing survival rate of patients with GC, and Cox multivariate regression analysis for prognostic factors of patients with GC. RESULTS: The frequency of HLA-DQB1*03 gene was increased in patients with GC. Patients with GC with HLA-DQB1*03 genotype had higher number of tumor size >6 cm, deeper depth of infiltration, higher LNM rate, and later stage of disease. Patients with HLA-DQB1*03 genotype had lower survival rate compared with other genotypes. Anemia before operation, depth of infiltration in T3 stage and T4 stage, LNM in N1 stage and N2 stage, and HLA-DQB1*03 genotype were regarded as independent risk factors for patients with GC. CONCLUSION: These results demonstrate that HLA-DQB1*03 genotype and perioperative blood transfusion are not conducive to the prognosis of patients with GC, which could provide a reference for the treatment of GC.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Cadeias beta de HLA-DQ/genética , Neoplasias Gástricas , Anemia , Feminino , Seguimentos , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia
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