RESUMO
UNLABELLED: Human papillomavirus 11 (HPV11) is an etiological agent of anogenital warts and laryngeal papillomas and is included in the 4-valent and 9-valent prophylactic HPV vaccines. We established the largest collection of globally circulating HPV11 isolates to date and examined the genomic diversity of 433 isolates and 78 complete genomes (CGs) from six continents. The genomic variation within the 2,800-bp E5a-E5b-L1-upstream regulatory region was initially studied in 181/207 (87.4%) HPV11 isolates collected for this study. Of these, the CGs of 30 HPV11 variants containing unique single nucleotide polymorphisms (SNPs), indels (insertions or deletions), or amino acid changes were fully sequenced. A maximum likelihood tree based on the global alignment of 78 HPV11 CGs (30 CGs from our study and 48 CGs from GenBank) revealed two HPV11 lineages (lineages A and B) and four sublineages (sublineages A1, A2, A3, and A4). HPV11 (sub)lineage-specific SNPs within the CG were identified, as well as the 208-bp representative region for CG-based phylogenetic clustering within the partial E2 open reading frame and noncoding region 2. Globally, sublineage A2 was the most prevalent, followed by sublineages A1, A3, and A4 and lineage B. IMPORTANCE: This collaborative international study defined the global heterogeneity of HPV11 and established the largest collection of globally circulating HPV11 genomic variants to date. Thirty novel complete HPV11 genomes were determined and submitted to the available sequence repositories. Global phylogenetic analysis revealed two HPV11 variant lineages and four sublineages. The HPV11 (sub)lineage-specific SNPs and the representative region identified within the partial genomic region E2/noncoding region 2 (NCR2) will enable the simpler identification and comparison of HPV11 variants worldwide. This study provides an important knowledge base for HPV11 for future studies in HPV epidemiology, evolution, pathogenicity, prevention, and molecular assay development.
Assuntos
Variação Genética , Genoma Viral , Papillomavirus Humano 11/genética , Infecções por Papillomavirus/virologia , Evolução Molecular , Genômica , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Papillomavirus Humano 11/classificação , Papillomavirus Humano 11/isolamento & purificação , Humanos , Funções Verossimilhança , Fases de Leitura Aberta , Filogenia , Polimorfismo de Nucleotídeo Único , Alinhamento de SequênciaRESUMO
UNLABELLED: Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution. IMPORTANCE: This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new, complete HPV6 genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease, and/or gender. We additionally identified several HPV6 lineage- and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within the L2 gene that is suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination, and molecular assay development studies.
Assuntos
Neoplasias do Ânus/genética , Variação Genética/genética , Genoma Viral/genética , Neoplasias de Cabeça e Pescoço/genética , Papillomavirus Humano 6/genética , Papillomavirus Humano 6/isolamento & purificação , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Ânus/complicações , Neoplasias do Ânus/virologia , Evolução Biológica , Linhagem da Célula , Feminino , Genômica/métodos , Genótipo , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Filogenia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/virologiaRESUMO
INTRODUCTION: The susceptibility to pulmonary tuberculosis (TB) is multifactorial, thus genetic factors such as HLA and immunoglobulins-like killer receptors (KIR) could be predisposed to the development of the disease. Aim To evaluate whether any HLA classi allele and its combination with KIR could be related to the development of TB in the Wichi Amerindian community in north-eastern Argentina. METHODS: A cohort study was conducted that included 18 families, 35 individuals affected with TB, 84 cohabiting families, and 63 controls of the same ethnic group. A and B loci of HLA classi were typed by generic PCR followed by reverse hybridization (Dynal), locus C by PCR-SSOP. KIR receptors were studied using sequence specific PCR. RESULTS: There was a highly significant association with allele B*35:19/47 in TB vs. household contacts [Pc=0.0051] and vs. controls [Pc=0.0033], and with allele HLA-C*03 in TB vs. household contacts [Pc=0.014] and vs. controls [Pc=0.0033]. KIR receptors had shown increased KIR2DL3/KIR2DL3 frequency in combination with the C1 group of HLA-C (P=.018). HLA-C*03 belongs to C1 group, and this combination could have a strong inhibitory action on the infected cell. CONCLUSION: HLA-B35:19/47-C*03 haplotype could be a susceptibility factor to TB and KIR2DL3-HLA-C1 combination have an inhibitory capacity on NK cells, and might contribute to the course of the infection by Mycobacterium tuberculosis.
Assuntos
Antígenos HLA/análise , Indígenas Sul-Americanos/genética , Receptores KIR/análise , Tuberculose Pulmonar/imunologia , Alelos , Argentina/epidemiologia , Frequência do Gene , Genes MHC Classe I , Predisposição Genética para Doença , Genótipo , Antígenos HLA/imunologia , Haplótipos/genética , Humanos , Imunidade Inata , Células Matadoras Naturais/imunologia , Receptores KIR/genética , Receptores KIR/imunologia , Subpopulações de Linfócitos T/imunologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/genéticaRESUMO
BACKGROUND: There is a strong association between celiac disease (CD) and certain genes of the major histocompatibility complex (HLA). The CD specifically related alleles are those coding for HLA-DQ2 heterodimer and to a lesser degree for HLA-DQ8. OBJECTVE. The aim of this study was to evaluate the frequency of HLA-DQB1* and HLA-DRB1* alleles, haplotypes, and genotypes in patients diagnosed with CD and in control population of Chaco, in order to establish its distribution and compare it with that observed in other populations. METHODS: A total of 139 samples from patients diagnosed with CD and 119 healthy controls were typed for HLA-DQ and HLA-DR, using PCR and reverse hybridization (INNO-LiPA or Dynal). RESULTS: Comparing patients with CD vs. controls, the DQBI*0201 (P = 0.0002), DQBJ*0202 (P = 0.0046), DQBI*0302 (P = 0. 0006), DRBl *03 (P = 0.0002), DRBl *04 (P = 0.0199) and DRB1 *07 (P = 0.0062) were significantly increased, while a decrease was observed in HLA-DQB1*0301 (P = 0.0006), HLA-DQBI*0303 (P = 0.0070), DQBI*0501 (P = 0.0023), DQB1*0604 (P = 0.0140) DRB1*01 (P = 0.0023), DRB1*08 (P = 0.0165), DRB1*09 (P = 0.0362) and DRB1*16 (P = 0.0228). Within DQB1* genotypes associated with EC, 65.4% of patients had the DQB1*02 in linkage disequilibrium with DRB1*03 or DRB1*07 (DQ2), and 43.2% presented genotype DQB1*0302 in linkage disequilibrium with DRB1*04 (DQ8). Both genotypes were shared by 15.2% of them. CONCLUSIONS: We point out the high frequency of DQ8 associated with CD. Although the DQ2 is still the most common, this finding could be attributed to the Amerindian influence in our population.
Assuntos
Doença Celíaca/genética , Predisposição Genética para Doença/genética , Antígenos HLA-DQ/genética , Cadeias HLA-DRB1/genética , Adolescente , Adulto , Idoso , Argentina , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Activating and inhibitory killer immunoglobulin-like receptors (KIR) and their ligands HLA-Bw4 (loci A and B) were studied by way of establishing whether they can contribute to protection against HIV-1 infection in highly exposed and persistently seronegative (HESN) patients. Twenty-three HIV-1 serodiscordant heterosexual couples, 100 HIV-1(+) patients and 200 healthy individuals were included in this retrospective case-control study. HLA typing was performed by means of PCR followed by sequence-specific oligonucleotide probe reverse hybridization. KIR3DL1 and KIR3DS1 were studied by PCR sequence-specific primers. The frequency of KIR3DS1(3DS1/3DL1)-Bw4 combination was significantly higher in HESN patients versus the discordant couples (P = 0·0003) and HIV-1(+) patients (P = 0·0001). Conversely, the KIR3DL1/KIR3DL1 homozygosity was significantly decreased in HESN patients versus the discordant couples (P = 0·00003), and HIV-1(+) patients (P = 0·00066). The frequency of HLA-A*32 and HLA-B*44 was higher in HESN versus their discordant couples (P = 0·009; P = 0·049), and HIV-1(+) patients (P = 0·00002; P = 0·0001). This had greater significance in combination with KIR3DS1 (3DS1/3DL1). KIR3DS1(3DS1/3DL1) could have a greater effect on protection against HIV-1 infection in HESN patients when bound to a specific HLA allele, in this case HLA-A*32 and HLA-B*44, both Bw4 alleles. The differences probably arise both in the HLA alleles and in the subtypes of KIR receptors depending on the ethnic group studied.
Assuntos
Predisposição Genética para Doença/genética , Infecções por HIV/genética , Antígenos HLA-B/genética , Receptores KIR/genética , Adulto , Alelos , Argentina , Epitopos , Feminino , Genótipo , Antígenos HLA-A/genética , Heterossexualidade , Humanos , MasculinoRESUMO
El virus del papiloma humano (HPV) es el agente etiológico de infecciones de transmisión sexual relacionadas con procesos oncogénicos genitales y orales. La biología molecular, mediante la identificación de los tipos virales involucrados, proporciona precisión diagnóstica con un enfoque epidemiológico. El objetivo de este estudio fue determinar la presencia de HPV en la mucosa oral de hombres con verrugas anogenitales y correlacionar los genotipos detectados en ambas muestras. Se estudiaron 26 pacientes varones con verrugas anogenitales que acudieron al Instituto de Dermatología de la ciudad de Resistencia (Argentina). La presencia de HPV en muestras orales y anogenitales se estudió mediante reacción en cadena de la polimerasa (PCR) y la genotipificación se realizó mediante PCR-RFLP. La prevalencia de HPV oral en pacientes con HPV anogenital fue del 46,2% (12/26). Se encontraron dieciocho genotipos con alto riesgo oncogénico en muestras orales de pacientes con infecciones únicas o múltiples y el tipo 16 fue el más frecuente (6 pacientes). Catorce genotipos en muestras orales fueron de bajo riesgo oncogénico, el más frecuente fue el tipo 6 (10 pacientes). En muestras anogenitales el genotipo 6 fue el más frecuente (13 pacientes), solo o en coinfección. Se encontró una alta prevalencia de HPV oral de malignidad de alto grado en nuestra población y coinfección con tipos oncogénicos. Las prácticas de sexo oral fueron la principal conducta de riesgo para la infección, lo que quedó demostrado por el hallazgo simultáneo del mismo tipo de HPV en muestras orales y anogenitales
The human papillomavirus (HPV) is the etiologic agent of sexually transmitted infections related to genital and oral oncogenic processes. Molecular biology provides accurate diagnosis with an epidemiological approach, by identifying the viral types involved. The objective of this study was to determine the presence of HPV in oral mucosa from men with anogenital warts and to correlate the genotypes detected in both samples. Twenty-six male patients suffering anogenital warts who attended to the Institute of Dermatology in Resistencia (Argentina) were studied. The presence of HPV in oral and anogenital samples was studied by PCR and genotyping was performed by PCR-RFLP. The prevalence of oral HPV in patients with anogenital HPV was 46.2% (12/26). Eighteen genotypes with high oncogenic risk were found in oral samples of patients with single or multiple infections and type 16 was the most frequent (6 patients). Fourteen genotypes in oral samples were of low oncogenic risk and the most frequent was type 6 (10 patients). In anogenital samples the genotype 6 was the most frequent (13 patients), alone or in co-infection. A high prevalence of high-grade malignancy oral HPV in our population and co-infection with oncogenic types were found. Oral sex practices were the main risk factor for infection, which was demonstrated by the simultaneous finding of the same HPV type in oral and anogenital samples
Assuntos
Humanos , Masculino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Papillomaviridae , Condiloma Acuminado/diagnóstico , Infecções por Papillomavirus , Saúde do Homem , Mucosa BucalRESUMO
The pathogenesis of infections clearly involves immunoregulatory host factors and products of Major Histocompatibility Complex (MHC) genes class II which present antigenic peptides to the T-cell receptor on CD4+ cells which in turn increase the production of specific antibodies and cytotoxic T lymphocytes. The objective of this study was to determine the frequency of the different alleles of HLA class II DQ and DR in HIV-1 infected patients of Caucasians with Guaraní and Toba genetic backgrounds in an effort to determine the prevalence of certain alleles which could signify a factor of susceptibility to or protection against HIV-1 infection. A total of 54 HIV-1 positive patients and 46 healthy control subjects participated in the HLA-DQB1 study while 54 HIV-1 (+) patients and 57 healthy controls were analyzed for HLA-DRB1. Both HLA-DQB1 and HLA-DRB1 genotyping were performed using PCR and sequence-specific reverse hybridization oligonucleotide probe and analyzed with the LiPA Key Typing System and LiPA software. HLA-DQB1*0203(P = 0.041) and DRB1*01(P = 0.05) exhibited a decreased frequency in HIV-1 (+) patients while HLA-DRB1*13 (P = 0.017) was observed more frequently. Several studies have reported different findings, depending on the populations analyzed. Our data show that there are HLA class II alleles associated with susceptibility or resistance to HIV-1 infection and that these differ among ethnic groups. We believe that our results differ from the other Caucasians populations due to the ethnic variability of Chaco inhabitants resulting from mixing between Caucasians and South American natives (Guaraníes and Tobas).
Assuntos
Alelos , Predisposição Genética para Doença , Infecções por HIV/genética , HIV-1 , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Argentina , Frequência do Gene , Infecções por HIV/imunologia , Humanos , Imunidade InataRESUMO
There are many factors that influence the pathogenesis of autoimmune disease of which host genetic factors play an important role. The aim of this study was to investigate the HLA Class I and II genes in a family with a high incidence of AID to establish whether they contribute to the development of these disease. Four of them had been diagnosed with SLE and one with AHA. The patients with SLE showed the presence of HLA-A*02 B*40 DRB1*04:07 DQB1*03:02 haplotype with a high statistical significance. This haplotype was not present in the healthy individuals and in the patient with AHA, although the DRB1*04:07 DQB1*03:02 haplotype (carried by both parents) was found in the AHA patients and one of the healthy individuals. We must consider how HLA Class I in linkage disequilibrium with HLA Class II may be involved in susceptibility or in the development of SLE. An extensive study in this population should be conducted to establish the true participation of the HLA Class I region.
Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Genes MHC da Classe II , Genes MHC Classe I , Adulto , Idoso , Argentina/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Linhagem , Grupos RaciaisAssuntos
Vírus BK/isolamento & purificação , Nefropatias/etiologia , Transplante de Rim , Infecções por Polyomavirus/etiologia , Complicações Pós-Operatórias/virologia , Infecções Tumorais por Vírus/etiologia , Viremia/etiologia , Argentina/epidemiologia , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Rim/patologia , Rim/virologia , Nefropatias/prevenção & controle , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/virologia , Complicações Pós-Operatórias/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/virologia , Urina/virologia , Carga Viral , Viremia/diagnóstico , Ativação ViralRESUMO
INTRODUCCIÓN: La susceptibilidad a la tuberculosis pulmonar (TB) es multifactorial, por lo que factores genéticos como las moléculas del complejo mayor de histocompatibilidad (CMH) y los receptores tipo inmunoglobulinas presentes en células NK (KIR) podrían predisponer al desarrollo de la misma. OBJETIVO: Evaluar si algún alelo de HLA clasei en combinación con determinados KIR podría estar relacionado con el desarrollo de TB en la comunidad amerindia Wichi en el noreste argentino. MÉTODOS: En un estudio de cohorte se incluyeron 18 familias, 35 individuos afectados con TB, 84 convivientes familiares y 63 controles sanos del mismo grupo étnico. Los loci A y B de HLA clase I se tipificaron mediante amplificación genérica seguida de hibridación reversa (Dynal), el locus C por PCR-SSOP. Los receptores KIR fueron amplificados con primers de secuencia específica SSP-PCR. RESULTADOS: Se observó una asociación altamente significativa con el alelo B*35:19/47 en TB vs. contactos familiares [Pc = 0,0051] y vs. controles [Pc = 0,0033] y con el alelo HLA-C*03 en TB vs. contactos [Pc = 0,014] y vs. controles [Pc = 0,0033]. Cuando se analizaron los receptores KIR, se observó aumento de la frecuencia KIR2DL3/KIR2DL3 en combinación con el grupo C1 de HLA-C (p = 0,018). C*03 pertenece al grupo C1, por lo que podemos pensar que esta combinación ejerza una fuerte acción inhibitoria sobre la célula infectada con Mycobacterium. CONCLUSIÓN: HLA-B35:19/47-HLA-C*3 podrían ser un factor de susceptibilidad a TB y la combinación KIR2DL3-HLA-C1, por su efecto inhibitorio sobre las células NK, podría contribuir al curso clínico de la infección por M. tuberculosis
INTRODUCTION: The susceptibility to pulmonary tuberculosis (TB) is multifactorial, thus genetic factors such as HLA and immunoglobulins-like killer receptors (KIR) could be predisposed to the development of the disease. Aim To evaluate whether any HLA class I were typed by generic PCR followed by reverse hybridization (Dynal), locus C by PCR-SSOP. KIR receptors were studied using sequence specific PCR. RESULTS: There was a highly significant association with allele B*35:19/47 in TB vs. household contacts [Pc = 0.0051] and vs. controls [Pc = 0.0033], and with allele HLA-C*03 in TB vs. household contacts [Pc = 0.014] and vs. controls [Pc=0.0033]. KIR receptors had shown increased KIR2DL3/KIR2DL3 frequency in combination with the C1 group of HLA-C (P = .018). HLA-C*03 belongs to C1 group, and this combination could have a strong inhibitory action on the infected cell. CONCLUSION: HLA-B35:19/47-C*03 haplotype could be a susceptibility factor to TB and KIR2DL3-HLA-C1 combination have an inhibitory capacity on NK cells, and might contribute to the course of the infection by Mycobacterium tuberculosis
Assuntos
Humanos , Tuberculose Pulmonar/genética , Antígenos HLA/análise , Receptores KIR/análise , Mycobacterium tuberculosis/patogenicidade , Marcadores Genéticos , Predisposição Genética para Doença , Indígenas Sul-AmericanosRESUMO
OBJECTIVES: Segregation analyses in several populations have suggested a relationship between specific human leukocyte antigen (HLA) class II alleles and the development of different types of leprosy. The aim of this study was to determine the frequency of HLA class II DR and DQ alleles among leprosy patients in Chaco province, northeast Argentina, in an effort to determine whether these alleles might be involved in the development of the multibacillary (MB) and paucibacillary (PB) forms of leprosy. PATIENTS AND METHODS: Samples from 89 leprosy patients (MB = 70, PB = 19) and 112 healthy control subjects were analyzed. The HLA-DRB1 and HLA-DQB1 alleles were determined by PCR amplification and reverse hybridization with sequence-specific oligonucleotide probes, and analyzed with the INNO-LiPA typing system and LiPA software. DQB1*0201/0202/0203 in patients with MB leprosy and DRB1*04 in patients with PB leprosy were detected at significantly lower frequencies as compared with the normal controls. RESULTS: These data indicate that DQB1* 0201/0202/0203 may be a protective factor in MB leprosy and DRB1*04 in PB leprosy. DISCUSSION: We attribute the differences between our findings and those of other authors to the fact that the Caucasian inhabitants of Chaco include a considerable mixture of South American natives (Guaraníes and Tobas).
Assuntos
Antígenos HLA-DQ/fisiologia , Antígenos HLA-DR/fisiologia , Hanseníase/epidemiologia , Adulto , Idoso , Alelos , Argentina/epidemiologia , Suscetibilidade a Doenças/etnologia , Suscetibilidade a Doenças/imunologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-DQ/análise , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Antígenos HLA-DR/análise , Antígenos HLA-DR/genética , Cadeias HLA-DRB4 , Humanos , Indígenas Sul-Americanos/genética , Indígenas Sul-Americanos/estatística & dados numéricos , Hanseníase/classificação , Hanseníase/genética , Hanseníase/imunologia , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , População Branca/genética , População Branca/estatística & dados numéricosRESUMO
UNLABELLED: A total of 220 individuals were included in this study, 112 HIV-seronegative healthy individuals and 108 HIV-1-infected patients involving: 18 AIDS patients with Toxoplasmic encephalitis (AIDS-TE), 49 AIDS patients without TE, and 41 asymptomatic patients, were genotyping for DR and DQ loci by molecular biology techniques. Fisher's Exact test was used for statistical analysis. HLA-DQB*0402 and DRB1*08 alleles were associated with a high risk to develop opportunistic infections with neurological involvement, mainly Toxoplasma encephalitis in relationship with subjects healthy (OR = 20.43; Pc = 7.0 x 10(-6) and OR = 11; Pc = 2.6 x 10(-4), respectively); in relationship with AIDS no TE (OR = 6.98; Pc = 0.028 and OR = 4.85; P = 0.012, Pc = 0.14) and with patients in asymptomatic stage (OR = 61.50, Pc = 8.4 x 10(-6) and OR = 19.38; Pc = 3.9 x 10(-4)), respectively. CONCLUSIONS: It was concluded that the presence of HLA-DQB*0402 and DRB1*08 alleles in HIV-1-positive patients could be considered risk factors for developing neurological opportunistic infections, mainly Toxoplasmic encephalitis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/genética , Encefalite/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Toxoplasmose Cerebral/genética , Infecções Oportunistas Relacionadas com a AIDS/complicações , Argentina/epidemiologia , Estudos de Casos e Controles , Encefalite/complicações , Frequência do Gene , Predisposição Genética para Doença , HIV-1 , Antígenos HLA-DQ/classificação , Cadeias beta de HLA-DQ , Antígenos HLA-DR/classificação , Humanos , Fenótipo , Toxoplasmose Cerebral/complicaçõesRESUMO
BACKGROUND: There is a strong association between celiac disease (CD) and certain genes of the major histocompatibility complex (HLA). The CD specifically related alleles are those coding for HLA-DQ2 heterodimer and to a lesser degree for HLA-DQ8. OBJECTVE. The aim of this study was to evaluate the frequency of HLA-DQB1* and HLA-DRB1* alleles, haplotypes, and genotypes in patients diagnosed with CD and in control population of Chaco, in order to establish its distribution and compare it with that observed in other populations. METHODS: A total of 139 samples from patients diagnosed with CD and 119 healthy controls were typed for HLA-DQ and HLA-DR, using PCR and reverse hybridization (INNO-LiPA or Dynal). RESULTS: Comparing patients with CD vs. controls, the DQBI*0201 (P = 0.0002), DQBJ*0202 (P = 0.0046), DQBI*0302 (P = 0. 0006), DRBl *03 (P = 0.0002), DRBl *04 (P = 0.0199) and DRB1 *07 (P = 0.0062) were significantly increased, while a decrease was observed in HLA-DQB1*0301 (P = 0.0006), HLA-DQBI*0303 (P = 0.0070), DQBI*0501 (P = 0.0023), DQB1*0604 (P = 0.0140) DRB1*01 (P = 0.0023), DRB1*08 (P = 0.0165), DRB1*09 (P = 0.0362) and DRB1*16 (P = 0.0228). Within DQB1* genotypes associated with EC, 65.4
of patients had the DQB1*02 in linkage disequilibrium with DRB1*03 or DRB1*07 (DQ2), and 43.2
presented genotype DQB1*0302 in linkage disequilibrium with DRB1*04 (DQ8). Both genotypes were shared by 15.2
of them. CONCLUSIONS: We point out the high frequency of DQ8 associated with CD. Although the DQ2 is still the most common, this finding could be attributed to the Amerindian influence in our population.
Assuntos
Antígenos HLA-DQ/genética , Cadeias HLA-DRB1/genética , Doença Celíaca/genética , Predisposição Genética para Doença/genética , Adolescente , Adulto , Adulto Jovem , Argentina , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Idoso , Masculino , Pessoa de Meia-IdadeRESUMO
Muchos factores se han involucrado en la patogénesis de las enfermedades autoinmunitarias, entre los cuales el fondo genético desempeña un papel importante. El objetivo fue investigar los genes de HLA Clase I y II en una familia con alta incidencia de enfermedades autoinmunitarias para establecer si estos podrían contribuir al desarrollo de estas enfermedades. Los pacientes diagnosticados de lupus mostraron la presencia del haplotipo HLA A*02, B*40, DRB1*04:07, DQB1*03:02 con alta significación estadística. En los individuos sanos y en el paciente con AHA este haplotipo no estuvo presente; en cambio, el haplotipo Clase II DRB1*04:07, DQB1*03:02, estuvo también en el paciente con AHA y en uno de los individuos sanos. Deberíamos considerar cómo HLA Clase I en desequilibrio de ligamiento con HLA Clase II podría estar involucrado en la susceptibilidad o el desarrollo de lupus eritematoso sistémico. Un estudio más extenso de esta población debería llevarse a cabo a fin de establecer la verdadera participación de la región de HLA Clase I (AU)
There are many factors that influence the pathogenesis of autoimmune disease of which host genetic factors play an important role. The aim of this study was to investigate the HLA Class I and II genes in a family with a high incidence of AID to establish whether they contribute to the development of these disease. Four of them had been diagnosed with SLE and one with AHA. The patients with SLE showed the presence of HLA-A*02 B*40 DRB1*04:07 DQB1*03:02 haplotype with a high statistical significance. This haplotype was not present in the healthy individuals and in the patient with AHA, although the DRB1*04:07 DQB1*03:02 haplotype (carried by both parents) was found in the AHA patients and one of the healthy individuals. We must consider how HLA Class I in linkage disequilibrium with HLA Class II may be involved in susceptibility or in the development of SLE. An extensive study in this population should be conducted to establish the true participation of the HLA Class I region (AU)
Assuntos
Humanos , Masculino , Feminino , Doenças Autoimunes/classificação , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Técnicas de Genotipagem/instrumentação , Técnicas de Genotipagem/métodos , Doenças Autoimunes/genética , Haplótipos , Haplótipos/genética , Haplótipos/fisiologiaRESUMO
Objetivo. En la lepra, el análisis de segregación en varias poblaciones humanas sugiere una relación de alelos particulares de los antígenos leucocitarios humanos (HLA) clase II con el desarrollo de las diferentes formas de la enfermedad. Con el objetivo de determinar si algún alelo de las moléculas de HLA clase II en la población de la provincia del Chaco, Argentina, podrían estar comprometidos en el desarrollo de algunas de las formas de lepra multibacilar (MB) y/o paucibacilar (PB), se determinó la frecuencia de los alelos de los loci DR y DQ en pacientes con lepra. Pacientes y métodos. Se analizaron 89 muestras de pacientes con lepra (MB 5 70; PB 5 19) y 112 controles sanos. Se determinaron los alelos del locus DR y DQ, utilizando amplificación genérica por reacción en cadena de la polimerasa (PCR) e hibridación reversa con oligonucleótidos específicos (LIPA KEY-INNOGENETICS). Se encontró una disminución en la frecuencia del alelo DQB1*0201/0202/0203 en pacientes con lepra multibacilar y disminución del alelo DRB1*04 en pacientes con lepra paucibacilar respecto a controles, ambos con significación estadística. Resultados. Según los resultados observados, DQB1*0201/0202/0203 podría ser un alelo de protección en la forma multibacilar de la lepra y el alelo DRB1*04 estaría relacionado con protección en lepra paucibacilar. Discusión. Pensamos que las diferencias halladas con otras poblaciones caucásicas reportadas por otros autores se deben a que la población chaqueña de origen caucásico tiene una fuerte mezcla con nativos de América del Sur, guaraníes y tobas (AU)
Objectives. Segregation analyses in several populations have suggested a relationship between specific human leukocyte antigen (HLA) class II alleles and the development of different types of leprosy. The aim of this study was to determine the frequency of HLA class II DR and DQ alleles among leprosy patients in Chaco province, northeast Argentina, in an effort to determine whether these alleles might be involved in the development of the multibacillary (MB) and paucibacillary (PB) forms of leprosy. Patients and methods. Samples from 89 leprosy patients (MB 5 70, PB 5 19) and 112 healthy control subjects were analyzed. The HLA-DRB1 and HLA-DQB1 alleles were determined by PCR amplification and reverse hybridization with sequence-specific oligonucleotide probes, and analyzed with the INNO-LiPA typing system and LiPA software. DQB1*0201/0202/0203 in patients with MB leprosy and DRB1*04 in patients with PB leprosy were detected at significantly lower frequencies as compared with the normal controls. Results. These data indicate that DQB1* 0201/0202/0203 may be a protective factor in MB leprosy and DRB1*04 in PB leprosy. Discusion. We attribute the differences between our findings and those of other authors to the fact that the Caucasian inhabitants of Chaco include a considerable mixture of South American natives (Guaraníes and Tobas) (AU)
Assuntos
Humanos , Hanseníase/fisiopatologia , Antígenos HLA-DQ/análise , Antígenos HLA-DR/análise , Reação em Cadeia da Polimerase , Estudos de Casos e Controles , Hanseníase/genéticaRESUMO
The pathogenesis of infections clearly involves immunoregulatory host factors and products of Major Histocompatibility Complex (MHC) genes class II which present antigenic peptides to the T-cell receptor on CD4+ cells which in turn increase the production of specific antibodies and cytotoxic T lymphocytes. The objective of this study was to determine the frequency of the different alleles of HLA class II DQ and DR in HIV-1 infected patients of Caucasians with Guarani and Toba genetic backgrounds in an effort to determine the prevalence of certain alleles which could signify a factor of susceptibility to or protection against HIV-1 infection. A total of 54 HIV-1 positive patients and 46 healthy control subjects participated in the HLA-DQB1 study while 54 HIV-1 (+) patients and 57 healthy controls were analyzed for HLA-DRB1. Both HLA-DQB1 and HLA-DRB1 genotyping were performed using PCR and sequence-specific reverse hybridization oligonucleotide probe and analyzed with the LiPA Key Typing System and LiPA software. HLA-DQB1*0203(P = 0.041) and DRB1*01(P = 0.05) exhibited a decreased frequency in HIV-1 (+) patients while HLA-DRB1*13 (P = 0.017) was observed more frequently. Several studies have reported different findings, depending on the populations analyzed. Our data show that there are HLA class II alleles associated with susceptibility or resistance to HIV-1 infection and that these differ among ethnic groups. We believe that our results differ from the other Caucasians populations due to the ethnic variability of Chaco inhabitants resulting from mixing between Caucasians and South American natives (Guaranies and Tobas) (AU)#S#a
Assuntos
Humanos , Alelos , Predisposição Genética para Doença , Infecções por HIV , HIV-1 , Antígenos HLA-D , Argentina , Frequência do Gene , Infecções por HIV , Antígenos HLA-DQ , Antígenos HLA-DR , Imunidade InataRESUMO
The pathogenesis of infections clearly involves immunoregulatory host factors and products of Major Histocompatibility Complex (MHC) genes class II which present antigenic peptides to the T-cell receptor on CD4+ cells which in turn increase the production of specific antibodies and cytotoxic T lymphocytes. The objective of this study was to determine the frequency of the different alleles of HLA class II DQ and DR in HIV-1 infected patients of Caucasians with Guaraní and Toba genetic backgrounds in an effort to determine the prevalence of certain alleles which could signify a factor of susceptibility to or protection against HIV-1 infection. A total of 54 HIV-1 positive patients and 46 healthy control subjects participated in the HLA-DQB1 study while 54 HIV-1 (+) patients and 57 healthy controls were analyzed for HLA-DRB1. Both HLA-DQB1 and HLA-DRB1 genotyping were performed using PCR and sequence-specific reverse hybridization oligonucleotide probe and analyzed with the LiPA Key Typing System and LiPA software. HLA-DQB1*0203(P = 0.041) and DRB1*01(P = 0.05) exhibited a decreased frequency in HIV-1 (+) patients while HLA-DRB1*13 (P = 0.017) was observed more frequently. Several studies have reported different findings, depending on the populations analyzed. Our data show that there are HLA class II alleles associated with susceptibility or resistance to HIV-1 infection and that these differ among ethnic groups. We believe that our results differ from the other Caucasians populations due to the ethnic variability of Chaco inhabitants resulting from mixing between Caucasians and South American natives (Guaraníes and Tobas).
RESUMO
The pathogenesis of infections clearly involves immunoregulatory host factors and products of Major Histocompatibility Complex (MHC) genes class II which present antigenic peptides to the T-cell receptor on CD4+ cells which in turn increase the production of specific antibodies and cytotoxic T lymphocytes. The objective of this study was to determine the frequency of the different alleles of HLA class II DQ and DR in HIV-1 infected patients of Caucasians with Guarani and Toba genetic backgrounds in an effort to determine the prevalence of certain alleles which could signify a factor of susceptibility to or protection against HIV-1 infection. A total of 54 HIV-1 positive patients and 46 healthy control subjects participated in the HLA-DQB1 study while 54 HIV-1 (+) patients and 57 healthy controls were analyzed for HLA-DRB1. Both HLA-DQB1 and HLA-DRB1 genotyping were performed using PCR and sequence-specific reverse hybridization oligonucleotide probe and analyzed with the LiPA Key Typing System and LiPA software. HLA-DQB1*0203(P = 0.041) and DRB1*01(P = 0.05) exhibited a decreased frequency in HIV-1 (+) patients while HLA-DRB1*13 (P = 0.017) was observed more frequently. Several studies have reported different findings, depending on the populations analyzed. Our data show that there are HLA class II alleles associated with susceptibility or resistance to HIV-1 infection and that these differ among ethnic groups. We believe that our results differ from the other Caucasians populations due to the ethnic variability of Chaco inhabitants resulting from mixing between Caucasians and South American natives (Guaranies and Tobas) (AU)#S#a
Assuntos
Humanos , Antígenos HLA-D/genética , Alelos , Predisposição Genética para Doença , Infecções por HIV/genética , HIV-1 , Infecções por HIV/imunologia , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Frequência do Gene , Imunidade Inata , ArgentinaRESUMO
BACKGROUND: There is a strong association between celiac disease (CD) and certain genes of the major histocompatibility complex (HLA). The CD specifically related alleles are those coding for HLA-DQ2 heterodimer and to a lesser degree for HLA-DQ8. OBJECTVE. The aim of this study was to evaluate the frequency of HLA-DQB1* and HLA-DRB1* alleles, haplotypes, and genotypes in patients diagnosed with CD and in control population of Chaco, in order to establish its distribution and compare it with that observed in other populations. METHODS: A total of 139 samples from patients diagnosed with CD and 119 healthy controls were typed for HLA-DQ and HLA-DR, using PCR and reverse hybridization (INNO-LiPA or Dynal). RESULTS: Comparing patients with CD vs. controls, the DQBI*0201 (P = 0.0002), DQBJ*0202 (P = 0.0046), DQBI*0302 (P = 0. 0006), DRBl *03 (P = 0.0002), DRBl *04 (P = 0.0199) and DRB1 *07 (P = 0.0062) were significantly increased, while a decrease was observed in HLA-DQB1*0301 (P = 0.0006), HLA-DQBI*0303 (P = 0.0070), DQBI*0501 (P = 0.0023), DQB1*0604 (P = 0.0140) DRB1*01 (P = 0.0023), DRB1*08 (P = 0.0165), DRB1*09 (P = 0.0362) and DRB1*16 (P = 0.0228). Within DQB1* genotypes associated with EC, 65.4
of patients had the DQB1*02 in linkage disequilibrium with DRB1*03 or DRB1*07 (DQ2), and 43.2
presented genotype DQB1*0302 in linkage disequilibrium with DRB1*04 (DQ8). Both genotypes were shared by 15.2
of them. CONCLUSIONS: We point out the high frequency of DQ8 associated with CD. Although the DQ2 is still the most common, this finding could be attributed to the Amerindian influence in our population.