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1.
Front Immunol ; 13: 875283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844516

RESUMO

The frequencies and diversities of human leukocyte antigen (HLA) alleles and haplotypes are representative of ethnicities. Matching HLA alleles is essential for many clinical applications, including blood transfusion, stem cell transplantation, and tissue/organ transplantation. To date, the information about the frequencies and distributions of HLA alleles and haplotypes among the Kinh Vietnamese population is limited because of the small sample size. In this study, more than 3,750 cord blood units from individuals belonging to the Kinh Vietnamese population were genotyped using PCR sequence-specific oligonucleotide (PCR-SSO) for HLA testing. The results of the study demonstrated that the most frequently occurring HLA-A, -B, -C, and -DRB1 alleles were A*11:01 (25%), A*24:02 (12.3%), A*02:01 (11.2); A*03:03 (8.95%), A*02:03 (7.81%), A*29:01 (7.03%); B*15:02 (15.1%), B*46:01 (10.7%), B*58:01 (7.65%), B*38:02 (7.29%); C*08:01 (17.2), C*07:02 (16.2%), C*01:02 (15.2), C*03:02 (8.3%), C*15:05 (6.13); DRB1*12:02 (31.0%), DRB1*09:01 (10.47%), DRB1*15:02 (7.54%); DRB1*07:01 (6.68%), DRB1*10:01 (6.63%), respectively, with the highest allele diversity level observed in locus B (93 alleles). The most frequent haplotypes of two-locus combinations of HLA-A-B, HLA-A-C, HLA-A-DRB1, HLA-B-C, HLA-B-DRB1, and HLA-C-DRB1 haplotypes were A*11:01-B*15:02 (7.63%), A*11:01-C*08:01 (7.98%), A*11:01-DRB1*12:02 (10.56%), B*15:02-C*08:01 (14.0%), B*15:02-DRB1*12:02 (10.47%), and C*08:01-DRB1*12:02 (11.38%), respectively. In addition, the most frequent haplotypes of three- and four-locus sets of HLA-A-B-C, HLA-A-B-DRB1, HLA-A-C-DRB1, HLA-B-C-DRB1, and HLA-A-B-C-DRB1 were A*11:01-B*15:02-C*08:01 (7.57%), A*11:01-B*15:02-DRB1*12:02 (5.39%), A*11:01-C*08:01-DRB1*12:02 (5.54%), B*15:02-C*08:01-DRB1*12:02 (10.21%), and A*11:01-B*15:02-C*08:01-DRB1*12:02 (5.45%), respectively. This study provides critical information on the frequencies and distributions of HLA alleles and haplotypes in the Kinh Vietnamese population, accounting for more than 85% of Vietnamese citizens. It paves the way to establish an umbilical cord blood bank for cord blood transplantation programs in Vietnam.


Assuntos
Sangue Fetal , Antígenos HLA , Alelos , Povo Asiático/genética , Sangue Fetal/fisiologia , Frequência do Gene , Antígenos HLA/sangue , Antígenos HLA/genética , Antígenos HLA-A/sangue , Antígenos HLA-A/genética , Antígenos HLA-B/sangue , Antígenos HLA-B/genética , Antígenos HLA-C/sangue , Antígenos HLA-C/genética , Cadeias HLA-DRB1/sangue , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , Vietnã
3.
Front Immunol ; 11: 614488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33633734

RESUMO

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for patients with malignant hematologic diseases. Killer immunoglobin-like receptor (KIR) expressed by NK cells is closely associated with the transplant outcomes, and it has been widely explored and debated for a few decades. Recently published studies have revealed that inhibitory KIRs (iKIRs) are educated by their cognate human lymphocyte antigen (HLA) ligands, and that decreased iKIR-HLA pairs post-transplantation may indicate a reduced NK cell function and impaired control of the primary disease. However, this theory still needs to be validated by additional clinical studies. Here we conducted a retrospective analysis of 246 patients who received haploidentical (haplo)-HSCT at our treatment center between January 2015 and June 2018. Our data suggests that decreased iKIR-HLA C pair post-HSCT correlated with a significantly higher risk of relapse [hazard risk (HR) = 2.95, p = 0.019] and reduced overall survival (OS) (HR = 3.74, p = 0.001) and disease-free survival (DFS) (HR = 4.05, p = 0.0004) in patients with myeloid disease. In conclusion, decreased iKIR-HLA C pair should be avoided during anti-thymocyte globulin (ATG)-based haplo-HSCT, especially for patients with myeloid disease.


Assuntos
Soro Antilinfocitário/imunologia , Antígenos HLA-C/sangue , Neoplasias Hematológicas/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva Local de Neoplasia/metabolismo , Receptores KIR/sangue , Adolescente , Adulto , Criança , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/imunologia , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Antígenos HLA-C/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virologia , Teste de Histocompatibilidade , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Receptores KIR/imunologia , Estudos Retrospectivos
4.
Ther Drug Monit ; 41(5): 634-639, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31107404

RESUMO

BACKGROUND: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. METHODS: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment. RESULTS: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). CONCLUSIONS: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.


Assuntos
Formação de Anticorpos/efeitos dos fármacos , Antígenos HLA-C/sangue , Psoríase/sangue , Psoríase/tratamento farmacológico , Ustekinumab/uso terapêutico , Biomarcadores/sangue , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Placenta ; 75: 27-33, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30712663

RESUMO

INTRODUCTION: The pathogenesis of preeclampsia may involve inadequate trophoblast invasion caused by excessive inhibition of uterine natural killer cells (uNK) by extravillous trophoblast cells (EVT). This may be the result of a combination of maternal killer-cell immunoglobin-like receptor (KIR) AA genotype and fetal human leukocyte antigen-C2 (HLA-C2) genotype. A few studies have reported a significantly increased frequency of the maternal KIR AA/fetal HLA-C2 combination in cases of preeclampsia compared to controls. METHODS: Study subjects were 259 cases of severe preeclampsia/eclampsia and 259 matched pregnant women without preeclampsia or eclampsia. All pregnancies were singleton pregnancies, and mothers were preferentially primigravidae. Blood samples from women and their newborns were obtained from the Danish National Birth Cohort (DNBC) and the Danish Neonatal Screening Biobank. Significant differences in the frequencies of KIR AA and HLA-C2 between cases and controls were investigated. RESULTS: No significant difference was observed between cases and controls in the frequency of maternal KIR AA (OR = 0.86, 95%CI = 0.60-1.23, P = 0.41), neither when the fetus carried an HLA-C2 allele (OR = 0.85, 95%CI = 0.52-1.38, P = 0.51), nor when the fetus carried an HLA-C2 allele more than its mother (OR = 0.75, 95%CI = 0.34-1.64, P = 0.47). CONCLUSION: The Results show no influence of HLA-C/KIR genetic variation on the risk of severe preeclampsia, contrary to what some previous studies have observed. An explanation could be that severe preeclampsia represents a separate pathological entity compared to mild preeclampsia.


Assuntos
Feto/imunologia , Antígenos HLA-C/sangue , Pré-Eclâmpsia/imunologia , Receptores KIR/sangue , Estudos de Casos e Controles , Feminino , Humanos , Pré-Eclâmpsia/sangue , Gravidez
7.
J Immunol Res ; 2019: 1342762, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32083138

RESUMO

Transylvania is a historical region in the northwestern part of Romanian with a rather heterogeneous population. Our study is the first to determine human leukocyte antigen (HLA) profiles in a large population sample from this region and to compare them with other European population groups. HLA genes were examined in 2,794 individuals using the Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) and Polymerase Chain Reaction Sequence-Specific Oligonucleotide (PCR-SSO) methods. All samples were tested for the HLA-A locus, 2,773 for HLA-B, 1,847 for HLA-C, and 2,719 for HLA-DRB1 loci. HLA gene frequency data from several European population groups (as presented in studies involving more than 1,000 individuals) served as reference in comparison with the local sample. The distribution of HLA genes in the studied population group was heterogeneous, as the Hardy-Weinberg equilibrium was statistically significant (P value < 0.01). The most common genes found in our sample group were A∗02 (0.27%), B∗35 (0.14%), C∗07 (0.25%), and DRB1∗11 (0.19%). The most common haplotype was A∗01~B∗08~C∗07~DRB1∗03 (1.26% in 1,770 individuals with complete data). This analysis confirmed the known heterogeneity of the Transylvanian population. The study indicates that the European population groups located in close vicinity (those from Serbia, Hungary, Wallachia, and Croatia) are genetically closest to the Transylvanian population.


Assuntos
Haplótipos , Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo Genético , Frequência do Gene , Genética Populacional , Antígenos HLA-A/sangue , Antígenos HLA-A/genética , Antígenos HLA-B/sangue , Antígenos HLA-B/genética , Antígenos HLA-C/sangue , Antígenos HLA-C/genética , Cadeias HLA-DRB1/sangue , Cadeias HLA-DRB1/genética , Antígenos de Histocompatibilidade Classe I/sangue , Humanos , Romênia/etnologia , População Branca/genética
8.
HLA ; 89(2): 98-103, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28102039

RESUMO

Chimerism is defined as the presence of 2 or more than 1 genetically distinct cell populations in an organism. Dispermic chimeras are derived from the fertilization of 1 or 2 matured nuclei by 2 sperms. We here report detection of a healthy and phenotypically normal female with normal ABO red blood cell typing in whom dispermic chimerism was suspected after 3 alleles were identified at multiple human leukocyte antigen (HLA) loci using molecular HLA analysis. Molecular HLA typing showed the donor to have 3 HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 alleles in blood, saliva and nail samples. In addition, 3 of her 9 short tandem repeat loci also showed to have 3 distinct alleles in blood, nail and saliva specimens. In all investigations, the third alleles were attributed to a dual paternal contribution. This case represents a dispermic chimerism, with 2 paternal and 1 maternal haplotypes variably distributed throughout body tissues in a healthy and phenotypically normal female without abnormalities in erythrocyte ABO blood group. The origin of this chimerism is probably due to the fertilization of a single egg and its polar body, or a parthenogenetic egg, by 2 sperms.


Assuntos
Alelos , Quimerismo , Genótipo , Padrões de Herança , Doadores não Relacionados , Sistema ABO de Grupos Sanguíneos/sangue , Sistema ABO de Grupos Sanguíneos/genética , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Feminino , Expressão Gênica , Antígenos HLA-A/sangue , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-B/sangue , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Antígenos HLA-C/sangue , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Cadeias beta de HLA-DP/sangue , Cadeias beta de HLA-DP/genética , Cadeias beta de HLA-DP/imunologia , Cadeias beta de HLA-DQ/sangue , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/sangue , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Voluntários Saudáveis , Transplante de Células-Tronco Hematopoéticas , Humanos , Repetições de Microssatélites , Unhas/química , Linhagem , Saliva/química , Taiwan
9.
Dis Esophagus ; 30(2): 1-7, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-26822871

RESUMO

Gastroesophageal reflux disease (GERD) may lead to Barrett's esophagus (BE). Previously, a large genome-wide association study found two germline markers to be associated with BE, FOXF1 rs9936833 (C allele) and MHC rs9257809 (A allele). This study evaluated whether these two polymorphisms are associated with gastroesphageal acid reflux as measured by 24-hour pH testing. Patients with acid reflux symptoms referred for esophageal manometry and 24-hour pH monitoring at University Health Network (Toronto, ON) were enrolled. DNA extracted from blood was genotyped using a Taqman Polymerase Chain Reaction (PCR) assay. DeMeester scores of ≥14.7 or prior evidence of reflux esophagitis on endoscopy defined individuals with esophageal acid reflux. Logistic regression analysis, adjusted for clinical risk factors, was used to calculate odds ratios with 95% confidence intervals for each polymorphism in relation to the presence of acid reflux. Of 182 patients, the median age was 50 years and 62% were female; 95 (52%) met the definition of GERD. In the multivariable analysis, both FOXF1 rs9936833 (OR = 1.82; 95%CI: 1.12-2.96; P = 0.02) and MHC rs9257809 (OR = 9.36; 95%CI: 2.92-29.99; P < 0.001) remained significantly associated with presence of acid reflux. When both polymorphisms were placed in the same model, the adjusted ORs were 2.10 (95%CI: 1.24-3.53; P = 0.005) and 10.95 (95%CI: 3.32-36.09; P < 0.001), respectively. The association for risk allele C in FOXF1 rs9936833 and risk allele A in MHC rs9257809 with the presence of acid reflux suggests a potential pathophysiologic mechanism for the role of genetic influences in BE development.


Assuntos
Esôfago de Barrett/genética , Fatores de Transcrição Forkhead/sangue , Refluxo Gastroesofágico/genética , Antígenos HLA-C/sangue , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Monitoramento do pH Esofágico/métodos , Feminino , Refluxo Gastroesofágico/sangue , Marcadores Genéticos , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fatores de Risco
10.
Clin Exp Med ; 17(1): 93-100, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26567007

RESUMO

The serum levels of soluble HLA class I antigens (sHLA-A, -B, -C and sHLA-G) were determined in 40 HCV genotype 1-infected patients before (T 0), after 3, 6, and 12 months (T 3, T 6, and T 12) of pegylated-IFN-α plus ribavirin therapy and 6 months (T 18) after the end of treatment. Twenty patients were sustained virological responders (SVR), and 20 were non-responders (NR). sHLA-A, -B, -C levels at T 0 were significantly higher in both SVR (mean 10.48 µg/ml) and NR (mean 11.87 µg/ml) patients as compared to healthy controls (mean 0.34 µg/ml, p < 0.0001) and HIV-infected subjects (mean 1.22 µg/ml, p < 0.0001). sHLA-G levels at T 0 were significantly higher in SVR (mean 24.78 ng/ml) and NR (mean 24.93 ng/ml) patients as compared to healthy controls (mean 10.34 ng/ml, p = 0.015 and p = 0.014, respectively) but were lower as compared to HIV-infected subjects (mean 48.00 ng/ml, p < 0.0001). The levels of sHLA-A, -B, -C and sHLA-G significantly decreased in SVR from T 0 to T 18 (mean 1.64 and 1.43 ng/ml, respectively, p < 0.0001) and correlated with HCV-RNA, AST, ALT, γGT, and ALP levels. The determination of soluble HLA class I levels could be proposed as a surrogate marker to discriminate SVR and NR HCV-infected patients during PEG-IFN-α plus ribavirin therapy.


Assuntos
Antivirais/uso terapêutico , Biomarcadores Farmacológicos/sangue , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , RNA Viral/antagonistas & inibidores , Ribavirina/uso terapêutico , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Coinfecção , Quimioterapia Combinada , Feminino , Expressão Gênica , HIV/efeitos dos fármacos , HIV/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Antígenos HLA-A/sangue , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-B/sangue , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Antígenos HLA-C/sangue , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Antígenos HLA-G/sangue , Antígenos HLA-G/genética , Antígenos HLA-G/imunologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/fisiologia , Hepatite C Crônica/genética , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , RNA Viral/biossíntese , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
11.
An Bras Dermatol ; 91(3): 284-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27438193

RESUMO

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


Assuntos
Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Adolescente , Adulto , Alopecia em Áreas/genética , Alopecia em Áreas/imunologia , Brasil , Estudos de Casos e Controles , Estudos Transversais , Feminino , Frequência do Gene/genética , Antígenos HLA-B/sangue , Antígenos HLA-B/genética , Antígenos HLA-C/sangue , Antígenos HLA-C/genética , Cadeias HLA-DRB1/sangue , Cadeias HLA-DRB1/genética , Antígenos de Histocompatibilidade Classe I/sangue , Antígenos de Histocompatibilidade Classe II/sangue , Humanos , Masculino , Pessoa de Meia-Idade , População Branca , Adulto Jovem
12.
An. bras. dermatol ; 91(3): 284-289, tab
Artigo em Inglês | LILACS | ID: lil-787286

RESUMO

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


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Brasil , Antígenos de Histocompatibilidade Classe I/sangue , Antígenos HLA-B/genética , Antígenos HLA-B/sangue , Antígenos HLA-C/genética , Antígenos HLA-C/sangue , Antígenos de Histocompatibilidade Classe II/sangue , Estudos de Casos e Controles , Estudos Transversais , População Branca , Alopecia em Áreas/genética , Alopecia em Áreas/imunologia , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/sangue , Frequência do Gene/genética
13.
Diabet Med ; 33(1): 91-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26031759

RESUMO

AIM: Killer immunoglobulin-like receptors (KIRs) and their interaction with HLA class I ligands have been shown to be associated with Type 1 diabetes mellitus. The aim of our study was to investigate the influence of KIR genes and their HLA-C ligands for susceptibility to Type 1 diabetes in patients from Eastern India. METHODS: A total of 135 patients with Type 1 diabetes and 98 healthy subjects from Eastern India were typed for KIR genes and HLA-C ligands using PCR-based genotyping. The frequencies of these genes were compared between patients and controls. RESULTS: Comparison of KIR genes between Type 1 diabetes patients and healthy subjects revealed significantly different frequencies of KIRs 2DL2 and 2DS4. The presence of HLA-C1 was negatively associated with disease. The presence of both HLA-C1 and -C2 showed a negative association with Type 1 diabetes, whereas the absence of C1 and presence of C2 was positively associated with disease. Stratification analysis of HLA-C ligands and KIRs showed significant associations between Type 1 diabetes and 2DL2+/C1-, 2DL2-/C1+, 2DL3+/C1+, 2DL3+/C1- and 2DS2+/C1-. CONCLUSIONS: Our results suggest that the interaction of KIRs with HLA-C ligands are significant and certain combinations contribute to susceptibility to and protection against Type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Antígenos HLA-C/sangue , Células T Matadoras Naturais/metabolismo , Polimorfismo Genético , Receptores KIR2DL2/genética , Receptores KIR2DL3/genética , Receptores KIR/genética , Alelos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Frequência do Gene , Estudos de Associação Genética , Antígenos HLA-C/genética , Antígenos HLA-C/metabolismo , Humanos , Índia , Ligantes , Células T Matadoras Naturais/imunologia , Receptores KIR/agonistas , Receptores KIR/sangue , Receptores KIR/metabolismo , Receptores KIR2DL2/agonistas , Receptores KIR2DL2/sangue , Receptores KIR2DL2/metabolismo , Receptores KIR2DL3/agonistas , Receptores KIR2DL3/sangue , Receptores KIR2DL3/metabolismo
14.
Postgrad Med J ; 91(1076): 309-14, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25947201

RESUMO

BACKGROUND: Childhood-onset psoriasis (COP), a distinct clinical entity, may be associated with HLA-Cw6 positivity and metabolic and cardiovascular complications. There is some evidence that HLA-Cw6 positivity is associated with more extensive or severe disease and that positivity is lower in Asian patients than in Caucasians. We describe the clinical profile, prevalence of the HLA-Cw6 allele, metabolic syndrome (MetS) and vitamin D deficiency in Indian patients with COP. METHODS: In this cross-sectional hospital-based study over 15 months (June 2010-August 2011), 108 consecutive patients with disease onset ≤16 years were enrolled. Demographic, clinical and laboratory data were collected. Patients were categorised as children with COP (CCOP; n=69) or adults with COP (ACOP; n=39). Disease severity was assessed using body surface area (BSA) involved and Psoriasis Area and Severity Index (PASI) score. RESULTS: The most common morphological type was chronic plaque psoriasis; follicular psoriasis was seen only in children. Adults with disease onset in childhood, when compared with CCOP, had later disease onset (11.0±4.0 vs 6.9±3.8 (mean±SD) years; p<0.0001) of greater severity (p=0.021) based on BSA involved. PASI scores were, however, similar in ACOP and CCOP. Body mass index was not associated with disease severity. Of the 83 who underwent HLA-C typing, 46 (55.4%) were positive; positivity was associated with guttate lesions (p=0.031), scalp involvement (p=0.004), greater BSA involvement (p=0.002) and higher PASI scores (p=0.013). Vitamin D deficiency, obesity and MetS were present in 77.4%, 10.7% and 14.5% of patients, respectively. CONCLUSIONS: Among Indian patients, CCOP have earlier disease onset than ACOP. HLA-Cw6 was associated with guttate psoriasis, scalp involvement and disease severity. Vitamin D deficiency was common.


Assuntos
Antígenos HLA-C/sangue , Psoríase/sangue , Idade de Início , Criança , Pré-Escolar , Estudos Transversais , Feminino , Antígenos HLA-C/genética , Humanos , Índia/epidemiologia , Masculino , Prevalência , Psoríase/epidemiologia , Psoríase/genética , Psoríase/imunologia , Índice de Gravidade de Doença
15.
Placenta ; 36(4): 433-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24951171

RESUMO

INTRODUCTION: This study is to investigate the distribution of inhibitory and activating killer-cell immunoglobulin-like receptors (KIRs) and the combination of KIR/human leukocyte antigen (HLA)-C in women with preeclampsia in the Chinese Han population. METHODS: A total of 271 patients and 295 controls were enrolled in our study. The inhibitory/activating KIR and HLA-C genes were detected using the PCR-SSP (polymerase chain reaction with sequence-specific primers) method. RESULTS: Our result showed that decreased numbers of individual activating KIR genes (2DS2, 2DS3, and 2DS5) were observed in women with preeclampsia. Furthermore, the gene frequency of total activating KIRs was significantly lower in patients compared with that of the controls (P = 0.03). The frequency of the KIR2DL1 gene was increased in women with preeclampsia when a homozygous HLA-C2 allele appeared in the fetus. CONCLUSION: The results suggest that a KIR genetic variation might influence the risk of preeclampsia. The lack of activating KIRs could possibly lower uterine natural killer (uNK) cell activation, thereby contributing to the pathogenesis of preeclampsia. Moreover, the imbalance of the inhibitory or activating signals at the maternal-fetal interface seems to play a regulatory role in the occurrence of preeclampsia.


Assuntos
Predisposição Genética para Doença , Antígenos HLA-C/genética , Histocompatibilidade Materno-Fetal , Pré-Eclâmpsia/genética , Receptores KIR2DL1/genética , Adulto , Alelos , Povo Asiático , China , Estudos de Coortes , Feminino , Sangue Fetal , Frequência do Gene , Estudos de Associação Genética , Antígenos HLA-C/sangue , Antígenos HLA-C/metabolismo , Homozigoto , Humanos , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/metabolismo , Gravidez , Receptores KIR/sangue , Receptores KIR/genética , Receptores KIR/metabolismo , Receptores KIR2DL1/sangue , Receptores KIR2DL1/metabolismo
17.
Int J Immunogenet ; 38(5): 403-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21797986

RESUMO

Contribution of killer cell immunoglobulin-like receptors (KIR) and their human leucocyte antigen (HLA) class I ligands in the pathogenesis of autoimmune diseases has been shown in several studies. In this study, the possible association of KIR genes, their known HLA ligands and compound KIR/HLA genotypes with ankylosing spondylitis (AS) was assessed. Combined KIR/HLA ligand genotyping was performed by a polymerase chain reaction-sequence-specific primers assay in 35 Iranian patients with AS, and genotypes were compared to those in 200 healthy individuals. The frequencies of telomeric cluster genes KIR2DL5A, KIR2DS1 and KIR3DS1 were significantly increased in AS patient group (P(c) = 0.0082, P(c) = 0.0195 and P(c) = 0.0328, respectively). Conversely, HLA-Bw4 ligand (the presence of one or more -B Bw4(Ile80) , -B Bw4(Thr80) and -A Bw4 epitopes) (P(c) = 0.0004) and HLA-B Bw4(Ile80) (P(c) = 0.053) were less frequent in these patients. Meanwhile, compound KIR/HLA genotype analyses revealed lower frequency of KIR3DL1+HLA-B Bw4(Ile80) (P(c) = 0.0343) and higher frequency of KIR2DS1+HLA-C2 (P(c) = 0.0308) combinations in patients with AS than in controls. In addition, the genotypes iKIR+HLA > aKIR+HLA (P(c) = .0308) and iKIR+HLA > aKIR (P(c) = 0.0258) were statistically less common, and genotypes iKIR+HLA = aKIR+HLA (P(c) = 0.0081) and iKIR+HLA < aKIR (P(c) = 0.077) were more common in patient group. Our findings suggest a role for excessive or inappropriate NK cell activation through 'KIR/HLA' system in AS disease.


Assuntos
Antígenos HLA-B/genética , Antígenos HLA-C/genética , Receptores KIR3DL1/genética , Receptores KIR/genética , Espondilite Anquilosante/genética , Adolescente , Adulto , Criança , Frequência do Gene , Predisposição Genética para Doença , Genética Populacional , Antígenos HLA-B/sangue , Antígenos HLA-C/sangue , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Receptores KIR/sangue , Receptores KIR3DL1/sangue
18.
J Clin Lab Anal ; 24(4): 269-72, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20626025

RESUMO

Etiopathology of psoriasis is not completely understood. Patients with psoriasis show elevated sensitivity to gluten. The aim of this study was to see the expression of celiac disease (CD)-associated antibodies gliadin IgA, gliadin IgG, and tissue transglutaminase IgA, and their correlation with HLA Cw6 in patients with psoriasis. The study comprised 56 patients with psoriasis and 60 healthy controls (HC). The levels of antibodies were detected by using ELISA technique and HLA Cw6 typing was carried out by microcytotoxicity method. HLA Cw6 was significantly expressed in psoriasis cases when compared with HC (P<0.05). CD-associated antibodies gliadin IgA/IgG and tissue transglutaminase IgA were significantly higher in the serum of patient with psoriasis when compared with HC (P<0.05, <0.05, and 0.01, respectively). Serum anti tissue transglutaminase IgA (anti tTG IgA) was significantly higher in females when compared with males and expressed more in elderly patients. There was a significant positive correlation among the antibodies (anti gliadin IgA with anti gliadin IgG: r=0.67, P<0.05; anti gliadin IgA with anti tTG IgA: r=0.45, P<0.05, anti gliadin IgG with anti tTG IgA: r=0.26, P<0.05, respectively), whereas insignificant with HLA Cw6. Our study concludes that latent CD or CD-associated antibodies were present in patients with psoriasis and also concludes that HLA Cw6 has no association with expression of these antibodies in patients with psoriasis.


Assuntos
Doença Celíaca/imunologia , Antígenos HLA-C/sangue , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Psoríase/imunologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Gliadina/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Transglutaminases/imunologia
19.
Int J Immunogenet ; 37(6): 467-75, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20637045

RESUMO

Human leucocyte antigen (HLA) genetic characteristic of different ethnic minorities would be useful for tracing the origin of modern human HLA matching in transplantation and disease associations. In this study, we reported HLA-A, -B, -C and -DRB1 alleles and haplotypes in the Bulang and Hani populations of southwestern China using a high-resolution polymerase chain reaction-Luminex (PCR-Luminex) typing method. A total of nine HLA-A, 22 HLA-B, 13 HLA-C and 18 HLA-DRB1 alleles were identified in the Bulang population, and 11 HLA-A, 25 HLA-B, 14 HLA-C and 19 HLA-DRB1 alleles were in the Hani population. Compared with other populations, the predominant A*1101-B*1502-DRB1*1202 haplotype in the Bulang and Hani populations was also common in Jinuo, Wa, Dai, Maonan and Vietnamese populations. The distribution of HLA genes indicate that Bulang and Hani populations belong to the Southeast Asia group and they have maintained their original genetic characteristics and kept a long genetic distance from other populations owing to founder effects and subsequent geographic isolation. In addition, the close relationship among ethnic groups in Yunnan province and the Thai and Vietnamese populations were confirmed, whereas the Mon-Kmer-speaking populations shared other common HLA alleles and haplotypes compared with other linguistic groups.


Assuntos
Etnicidade/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DR/genética , Alelos , Sudeste Asiático , Povo Asiático/genética , China , Frequência do Gene , Genes MHC Classe I , Genes MHC da Classe II , Genótipo , Antígenos HLA-A/sangue , Antígenos HLA-B/sangue , Antígenos HLA-C/sangue , Antígenos HLA-DR/sangue , Cadeias HLA-DRB1 , Haplótipos , Teste de Histocompatibilidade , Humanos , Idioma , Fenótipo , Filogenia , Reação em Cadeia da Polimerase
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