RESUMO
El sistema de antígenos leucocitarios Humano (Human Leukocyte Antigen, HLA) regula la respuesta inmune mediante su unión a moléculas como el receptor de células T, participando en la presentación de antígenos y el reconocimiento de lo propio en el organismo. La caracterización genética del sistema HLA en determinada población es de gran utilidad para la comprensión de mecanismos asociados a susceptibilidad o resistencia a enfermedades y en la selección de donantes/receptores en trasplantes de órganos. En este estudio se planteó determinar la frecuencia de los Haplotipos HLA de clase I presentes en individuos sanos, relacionados familiarmente y venezolanos de tercera generación y su correspondiente desequilibrio de ligamiento. Se incluyeron 765 individuos pertenecientes a 218 familias a los cuales se les realizó tipificación HLA A y HLA B por PCR-SSOP (polymerase chain reaction-sequence specific oligonucleotide probe) en baja resolución. Se identificaron 265 haplotipos de los cuales los más frecuentes fueron HLA A*24 B*35 (11,98 %), A*02 B*51 (9,7%) y A*02 B*35 (8,6 %).Para los cálculos de desequilibrio de ligamiento se consideraron las frecuencias mayores al 1% (28,7%) y no arrojaron valores estadísticamente significativos el 6,78% de estos haplotipos. Los resultados obtenidos corroboran la composición triétnica históricamente conocida de nuestra población, en la cual predominan genes caucásicos, amerindios y afrodescendientes; y su porcentaje marca la diferencia con otras poblaciones americanas estudiadas. Estos resultados representan una aproximación de la conformación genética establecida en Venezuela y aporta datos que podrán ser usados como referencia en programas de salud para la población.
The system of Human leukocyte antigens (HLA) is the most polymorphic in humans. Its function is performed by regulating the immune response by binding to molecules such as T-cell receptor, involved in antigen presentation and recognition of the same in the body. Genetic characterization of HLA system in a given population is useful for understanding the mechanisms associated with susceptibility or resistance to various diseases and selection of donors and recipients in organ transplants, among others. The objective of the present study is to determine the frequency of HLA Class I Haplotypes present in healthy individuals, family relationships and third-generation Venezuelan and their corresponding linkage disequilibrium. We included 765 individuals belonging to 218 families who underwent HLA typing HLA A and B by PCR-SSOP (polymerase chain reaction-sequence specific oligonucleotide probe) in low resolution. 265 haplotypes were identified of which the most frequent were HLA A * 24 B * 35 (11.98%), A * 02 B * 51 (9.7%) and A * 02 B * 35 (8.6%). Calculations of linkage disequilibrium were considered frequencies above 1% (28.7%) and did not show statistically significant the 6.78% of these haplotypes. The results support the historically known tri-ethnic composition of our population, in which genes predominantly Caucasian, Mongoloid and Negroid, and make a difference with other American populations studied. These data can be used as reference to applications of benefit to this population.
RESUMO
Introducción: Un evento inmunopatológico característico en la hepatitis autoinmune (HAI) es la activación prolongada de la respuesta Th1. Diferentes promotores genéticos pueden predisponer a esta activación provocando ruptura de la inmunotolerancia. Uno de estos promotores es ICOS perteneciente a la familia de CD28, moléculas involucradas en funciones que regulan las respuestas Th1 y Th2 previniendo la activación prolongada de la respuesta Th1. Objetivo: Determinar el polimorfismo del gen ICOS (c.1564 T/C) en pacientes mestizos venezolanos con HAI tipo 1 y su posible asociación con la expresión clínica. Materiales y Métodos: Se investigaron 70 pacientes con HAI tipo 1 y 121 individuos sanos, ambos grupos venezolanos de tercera generación. La determinación del polimorfismo se realizó mediante reacción en cadena de la polimerasa (PCR) seguida por polimorfismos en la longitud de los fragmentos de restricción (RFLP). Resultados: El alelo silvestre T fue el más frecuente tanto en pacientes como en controles siendo mayor en el segundo grupo (60,7% vs 70,4%; p=0,05; pc=ns OR 1,45 p<0,05). El alelo mutado C se observó más en los pacientes con respecto al grupo control (39,3% vs 29,6%; p=0,05; pc=ns OR 1,45 (p<0,05). En las frecuencias genotípicas, se demostraron los genotipos heterocigotos (T/C) y homocigotos para el alelo mutado (C/C) más prevalentes en el grupo de pacientes que en controles y el genotipo silvestre T/T más frecuente en controles que en pacientes siendo estas diferencias significativas al 10% (χ2=5,31;2GL;p=0,07); OR 2,08 (p<0,05). Los pacientes con el genotipo heterocigoto demostraron niveles más elevados de globulinas, de IgG y mayor presencia de anticuerpos anti-mitocondriales que los observados en el genotipo T/T con diferencia estadística significativa al 10%. Además, se observa menor presencia de anticuerpos antinucleares en el genotipo T/C vs. T/T (p<0,10; pc=ns). Conclusiones: En el estudio del polimorfismo del gen ICOS (c.1564 T/C) los genotipos heterocigoto T/C y homocigoto mutado C/C son más frecuentes en pacientes mestizos venezolanos con HAI tipo 1 que en controles con riesgo significativo. Este polimorfismo se asocia a ciertas variables inmunodiagnósticas.
Introduction: A characteristic immunopathological event in autoinmune hepatitis (AIH) type 1 is the prolonged activation of Th1 response. Different promoters might predispose to this activation inducing immunotolerance breaking. ICOS is one of these promoters which belong to CD28 family, molecules involved in Th1 and Th2 regulating functions to prevent Th1 longer activation. Objective: To determine gen ICOS (c.1564 T/C) polymorphism in Venezuelan mestizo patients with AIH type 1 and its possible association with clinical expression. Materials and Methods: Seventy patients with AIH type 1 and 121 healthy individuals, both third generation Venezuelan groups, were investigated. Polymorphism determination was performed by polymerase chain reaction (PCR) following by restriction fragments longitudinal polymorphisms (RFLP). Results: The most frequent allele was wild T either in patients and controls, being higher in the second group (60,7% vs. 70,4%; p=0,05; pc=ns OR 1,45 p<0,05). The mutant C allele was observed more in patients than controls (39,3% vs. 29,6%; p=0,05; pc=ns OR 1,45 (p<0,05). In the genotypes frequencies, heterozygote genotypes (T/C) and homozygote mutant allele (C/C) were prevalent in the patients group while in the control´s group the wild genotype T/T was the most frequent being these differences significantly to 10% (χ2=5,31;2GL;p=0,07); OR 2,08 (p<0,05). Compared to the T/T genotype group, patients with heterozygote genotype shown higher levels of globulins, IgG and presence of anti-mithocondrial antibodies with a significant difference to 10%. Moreover, presence of antinuclear antibodies was less frequent in the T/C genotype vs. T/T (p<0,10; pc=ns). Conclusion: Heterozygote genotype T/C and homozygote mutant genotype C/C of gen ICOS (c.1564 T/C) with a significantly risk are more frequent in Venezuelan mestizo patients with AIH type 1 than in controls with a significantly risk. This polymorphism is associated with certain immunodiagnostic variables.
RESUMO
La sensibilización y las manifestaciones alérgicas al maní se han incrementado últimamente a nivel mundial, constituyendo el mismo la causa principal de anafilaxia por alimentos. Como la prevalencia de alergia al maní varía de acuerdo a las regiones nos propusimos evaluar, en una etapa preliminar, la sensibilización al maní por pruebas cutáneas (skin prick test) en pacientes venezolanos atópicos y/o con urticarias que acudieron a la Consulta ambulatoria de Alergía del Instituto de Inmunología. El 5,4 % de los pacientes manifestó algún tipo de manifestación cutánea o respiratoria al ingerir maní. Se demostró sensibilización al maní por pruebas cutánea en el 6,5 % de los pacientes. Sin embargo, un porcentaje pequeño (2 %) de ellos mostró, en conjunto, pruebas cutáneas positivas y síntomas a la ingesta del maní. Ningún paciente refirió síntomas severos tras la ingestión de maní. La mayoría de los pacientes con pruebas positivas al maní, también mostraron pruebas positivas a otros alimentos. Estos resultados concuerdan con la percepción de los médicos venezolanos de una baja frecuencia de reacciones adversas, especialmente graves, a la ingesta de maní en nuestro país
Peanut allergy and sensitization incidence has increased world wide to become the first cause of food anaphylaxis. Since the prevalence of peanut allergy changes according to geographical areas, the aim of the study was to assess, in a preliminary report, peanut allergy incidence by skin prick test in atopic Venezuelan patients with atopy and or urticaria from the outpatient allergy clinic of the Institute of Immunology. Cutaneous or respiratory manifestations after peanut ingestion was observed in 5.4 % of the patients studied. Cutaneous test was positive in 6.5 % of patients. In the other hand, a small group (2 %), showed positive skin test along with symptoms after peanut ingestion. None of the patients had severe reactions. Most of the patients with peanut positive skin test were positive to other food allergens. These results are in accordance with the general clinical perception of small frequency of adverse reaction, specially the most serious ones, to peanut ingestion in our country
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Arachis/efeitos adversos , Arachis/imunologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/patologia , Testes Imunológicos/métodos , Urticária/imunologia , Urticária/patologia , Alergia e ImunologiaRESUMO
Population studies represent an integral part and link in understanding the complex chain of host-pathogen interactions, disease pathogenesis, and MHC gene polymorphisms. Genes of Mongoloid, Caucasoid, and Negroid populations have created a distinctive HLA genetic profile in the Venezuelan population. Our objective was to determine the predominant HLA class I and II alleles and haplotype frequencies in the hybrid population of Venezuela. The study population consisted of 486 healthy unrelated native Venezuelans and 180 families. We examined the frequency of HLA A-B-C, HLA-DQ and HLA-DR genes by polymerase chain reaction and subsequent hybridization with sequence-specific oligonucleotide probes. Phenotypic, allelic and haplotype frequencies were estimated by direct counting and using the maximum-likelihood method. The predominant HLA class I alleles were A*02, A*24, A*68, B*35, B*44, B*51, B*07, B*15 and Cw*07. Regarding HLA class II, the most frequent alleles were DQB1*03 and DRB1*04, DRB1*15, DRB1*13, DRB1*07. The prevailing haplotype was HLA-A*02B*35 DQB1*03 DRB1*04. Some of these alleles and haplotype frequencies were predominantly present in Amerindians (A*02, A*24, B*35, Cw*07, DRB1*04, A*24 B*35). Previous reports have shown high incidence of A*02, B*44, B*51, DRB1*15, DRB1*13, DRB1*07 alleles in several European populations and A*68, B*07, B*15 alleles in African Americans, which could have contributed to the ethnic admixture of the Venezuelan population. We conclude that our results provide strong evidence that Venezuela's population represents an admixture of the primitive Mongoloid Aborigines, Caucasoid Europeans and Western African Negroid migrants.
Assuntos
Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Alelos , Etnicidade/genética , Etnicidade/estatística & dados numéricos , Frequência do Gene , Genética Populacional , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Haplótipos , Teste de Histocompatibilidade , Humanos , Venezuela/epidemiologiaRESUMO
: Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide.
RESUMO
Introducción: La Hepatitis Autoinmune (HAI) tipo 1 es una enfermedad hepática progresiva en la cual se demuestra susceptibilidad genética asociada a determinantes compartidos de moléculas HLA clase II. Sin embargo, 30 a 50% de estos pacientes, no asocian alelos HLA de susceptibilidad por lo que otros promotores genéticos que pudiesen predisponer a la ruptura de inmunotolerancia están siendo investigados. La Proteína Linfoide Tirosina Fosfatasa (LYP) codificada por el gen PTPN22, ejerce una potente inhibición en el linfocito T activado. El polimorfismo de este gen en la posición 1858 (sustitución de citosina (C) por una timina (T)) se describe asociada a múltiples patologías autoinmunes pero aún no se ha reportado en HAI tipo 1. Objetivo: Determinar la posible asociación del polimorfismo del gen PTPN22 en mestizos venezolanos con HAI tipo 1. Material y Métodos: Nuestra población consistió de 62 pacientes con HAI tipo 1 y 107 individuos sanos, ambos grupos venezolanos de tercera generación. La determinación del polimorfismo se realizó mediante la amplificación de la región en estudio (posición 1850 del codón 620) con la técnica de PCR estandarizada seguida por digestión de enzimas de restricción (Xcm I). Resultados: El genotipo más frecuente fue el genotipo homocigoto silvestre (C/C) tanto en pacientes (90.3%) como en controles (98.1%,) sin diferencia significativa. El polimorfismo C1858T (genotipo C/T) del gen PTP22 se identificó con mas frecuencia en los pacientes con diferencia estadísti-camente signifi cativa al relacionarlo con el grupo control (p= 0.029, OR=5,6). El genotipo homocigoto TT no se observó en ninguno de los individuos estudiados. Conclusión: El polimorfismo del gen PTPN22 a nivel C1858T descrito en otras enfermedades de origen au-toinmune también se detecta en HAI tipo 1, probable-mente confiriendo susceptibilidad a esta enfermedad en la población mestiza venezolana.
Background: Autoimmune hepatitis (AIH) type 1 is a progressive inflammatory disorder of the liver with genetic association to human leukocyte antigens. How-ever, the genetic background of AIH type 1 is considered to be polygenic. Lymphoid tyrosine phosphatase, encoded by the PTPN22 gene, exerts an important down regulatory effect on T cell activation in immune response. The single nucleotide polymorphism C1858T within the PTPN22 gene has been associated with in-creased susceptibility to a number of autoimmune dis-orders. Objective: The aim of this study was to assess the association of the single nucleotide polymorphism C1858T of the PTPN22 gene in Venezuelan Mestizos patients with AIH type 1. Materials and Methods: 62 Venezuelan Mestizos patients with AIH type 1 and 107 healthy volunteers were investigated. Cases and controls were genotyped for C1858T polymorphism by restriction fragment length polymorphism analysis of PCR products. Results: The wild-type C/C homozygous genotype was the most common variant in both patients (90.3 %) and controls (98.1 %). The heterozygous genotype C/T was significantly found in AIH patients compared to controls (OR = 5.6, P = 0.029). The T/T homozygous mutant genotype was not observed in either population. Conclusions: These results suggest that the PTPN22 1858C/T genotype could confer differential susceptibility to AIH type 1 in Venezuelan Mestizos patients. In addition, these findings provide strong evidence that lymphoid tyrosine phosphatase could be a critical player in multiple autoimmune disorders.
Assuntos
Humanos , Masculino , Adulto , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/genética , Hepatite Autoimune/virologia , Linfócitos T , DNA , Gastroenterologia , Sistema ImunitárioRESUMO
OBJECTIVE: : To determine the effectiveness of desloratadine syrup in relieving symptoms of allergic rhinitis (AR) among children in Latin America. METHODS: : In an open-label trial conducted in 5 Latin American countries, 455 children aged 6 to 12 years with seasonal or perennial AR were treated with desloratadine syrup 2.5 mg/d for 6 weeks. Thirty percent of subjects were concomitantly taking corticosteroids, and 21.3% had a history of asthma. Efficacy was measured by improvement in the Total Symptom Severity 4 questionnaire and decrease in severity of individual nasal symptoms of congestion, rhinorrhea, pruritus, and sneezing. Physicians and subjects' caregivers rated symptom improvement in a separate assessment at final visit. RESULTS: : Treatment with desloratadine led to a significant decrease in mean Total Symptom Severity 4 score, from 7.54 at baseline to 1.96 at study end (P < 0.0001), and in individual symptom scores, including congestion (P < 0.0001 for all). Similar improvements were found in groups receiving desloratadine monotherapy and desloratadine plus corticosteroids. Allergic rhinitis symptoms were rated "better" or "much better" by 94% of caregivers. Incidence of adverse events was 6%. CONCLUSIONS: : Desloratadine, with or without concomitant corticosteroids, was efficacious and safe in the treatment of AR in this group of Latin American children.
RESUMO
AIMS: Autoimmune hepatitis (AIH) is a progressive liver disease characterized by the presence of circulating autoantibodies, hypergammaglobulinaemia and a favourable response to immunosuppressive treatment. Although the pathogenesis of type 1 AIH is unknown, disease susceptibility is partially determined by genes linked to the class II region of the major histocompatibility complex. Type 1 AIH has been associated with DRB1*03, DRB1*04 and DRB3 alleles in European and North American Caucasians, with DRB1*0405 in Japanese, with DRB1*0404 in Mexican, and with DRB1*1301 in Argentinean populations. METHODS: To analyse the molecular basis of these associations in Venezuela (mestizo population), we examined the frequency of human leucocyte antigens (HLA)-A -B -C, HLA-DQ and HLA-DR genes by low- and high-resolution oligonucleotide typing in a population of 41 type 1 AIH patients and 111 ethnic- and aged-matched healthy subjects. RESULTS: The frequencies of both DRB1(*)1301 (P<0.0001) and DRB1*0301 (P<0.005) were significantly higher in patients than in controls. In addition, patients showed a strong association with the DRB3 allele (P<0.01). In contrast, the DQB1*04 allele was significantly decreased in the patient group (P<0.01). The frequencies of haplotypes A*01-B*08-DQB1*02-DRB1*03-DRB3, DQB1*05-DRB1*1301, DQB1*06-DRB1*1301 and A*02-DRB1*1301, B*45-DRB3 were significantly increased in type 1 AIH patients compared with the controls (P<0.01). CONCLUSIONS: In conclusion, our data indicate that type 1 AIH predisposition in a Venezuelan mestizo population of different ethnic backgrounds is associated with DRB1*1301 and DRB1*0301 alleles. In addition, our findings suggest that protection against disease might be conferred by the DQB1*04 allele, with distinct ethnic differences from other populations.
Assuntos
Hepatite Autoimune/genética , Hepatite Autoimune/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Indígenas Sul-Americanos/genética , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Criança , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Haplótipos , Hepatite Autoimune/etnologia , Humanos , Indígenas Sul-Americanos/estatística & dados numéricos , Cirrose Hepática/genética , Cirrose Hepática/imunologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Venezuela/epidemiologiaRESUMO
Exposure to fungi in the indoor environment may trigger hypersensitivity to a variety of fungi and is known to be an influencing factor in allergic rhinitis and asthma. A wide list of airborne fungal spores and dust containing fungi have been described for different environments; however, their clinical relevance is seldom clear. In this survey we measure levels of fungi indoor and outdoor of domestic dwellings of 10 patients with known chronic allergic respiratory disease to fungi. To measure hypersensitivity to fungi, Prick (sensitivity to fungi), RAST (specific serum IgE levels) and PAR (persistent allergic rhinitis) severity are assessed in relation to fungal load in the environment. Only association of PAR and indoor fungal load were found to be significant (P = 0.1648). No direct causality with sensitivity to the amount of exposure, or a hypersensitivity to a specific fungal genus could be established. There is still no consensus on the most relevant methods for measuring personal exposure and 'no safe levels' have been established yet.