Caracterización inmunogenética de donantes cadavéricos cubanos en el año 2019 / Immunogenetic characterization of Cuban cadaveric donors in 2019

Introducción: El trasplante es la opción terapéutica más favorable para las personas con insuficiencia renal crónica. El donante puede ser cadavérico o donante vivo, emparentado o no. Los resultados del trasplante están en relación con varios factores inmunológicos y no inmunológicos. Objetivo: Caracterizar inmunogenéticamente a los donantes cadavéricos cubanos para trasplante renal. Métodos: Se realizó un estudio transversal y descriptivo de los donantes cadavéricos durante el año 2019. Se analizó la región de procedencia, sexo, color de la piel y rangos de edades de los donantes, así como, grupo sanguíneos ABO y Rhesus Rh; serología para VIH, Virus de hepatitis B(VHB) y Virus de hepatitis C (VHC); y hábitos tóxicos. Resultados: Se estudió un total de 95 donantes cadavéricos, 62 provenientes del occidente y 33 del centro del país. El 63,2 por ciento fueron masculinos y 36,8 por ciento femenino. El grupo de edad de mayor frecuencia fue 40 - 60 años y la edad media de 49,45 años. El 58,95 por ciento de los pacientes fueron de grupo sanguíneo O; 30,53 por ciento grupo A y los grupos B y AB tuvieron 5,26 por ciento de prevalencia; y solo 8 fueron Rh negativos. Todos tuvieron serología para VIH, VHB y VHC negativas. Las enfermedades asociadas más frecuentes fueron la hipertensión arterial y la diabetes mellitus. Conclusiones: Los donantes cadavéricos durante el año 2019 mostraron características similares a las reportadas por otros estudios. El aumento de las edades de los donantes incide en la aparición de enfermedades asociadas y esto pudiera repercutir en el resultado del trasplante(AU)

Introduction: Transplantation is the most favorable therapeutic option for people with chronic renal failure. The donor can be a cadaveric or living donor, related or not. Transplant outcomes are related to various immunological and non-immunological factors. Objective: To characterize Cuban cadaveric donors for renal transplantation Materials and methods: A cross-sectional and descriptive study of cadaveric donors was carried out during the year 2019. The region of origin, sex, skin color and age ranges of the donors were analyzed, as well as ABO and Rhesus Rh blood groups; serology for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV), and toxic habits. Results: A total of 95 cadaveric donors were studied, 62 from the West and 33 from the Center of the country. 63.2 percent were male and 36.8 percent female due to the most frequent age group being 40-60 years and the mean age of 49.45 years. 58.95 percent of the patients were of blood group O, 30.53 percent group A and groups B and AB had 5.26 percent prevalence; and only 8 were Rh negative. All had negative serology for HIV, HBV and HCV. The most frequent associated diseases were arterial hypertension and diabetes mellitus. Conclusions: The cadaveric donors during the year 2019 showed characteristics similar to those reported by other studies. The increase in the age of the donors affects the appearance of associated diseases and this could affect the result of the transplant(AU)

Analysis of the Frequency of the Toll-like 2 Gene Polymorphism in Leprosy

Polymorphisms in genes that are responsible for encoding cytokines and receptors involved in the immune response, such as Toll-like Receptor (TLR) 2 in leprosy, are of great interest for immunogenetic studies. This work aimed to analyze the possible association of single nucleotide polymorphism (SNP), synonymous, rs3804100 of the TLR2 gene with leprosy. The study was conducted in Bacteriology and Mycology section of Evandro Chagas Institute, Brazil between August 2020 and July 2021.The scope of the study consisted of 122 subjects from cities of Goian閟ia, Rondon, Curion髉olis, Altamira, Parauapebas and Reden玢o of the State of Par�, Brazil. Genotyping was performed by conventional PCR and sequencing in the ABI 3130 Genetic Analyzer (Applied Biosystems�) using primer nucleotides designed by the Primer3Plus program from the genomic region 揌omo sapiens toll like receptor 2 (TLR2) transcript variant X6, mRNA�, deposited in GenBank with reference XM_011532216.2. The analyzes were performed based on Fisher's exact test. It was managed in accordance with Helsinki Declaration and the Brazilian National Health Council and with approval of the ethics committee at Evandro Chagas Institute, under opinion number: 3.950.570. No associations between gender and leprosy were possible (P> 0.05). However, associations were observed between age groups, which were significant between those over 46 years old (P=0.004) and the 2nd dose of BCG as a more protective agent between the groups analyzed (P=0.004). For the subjects with the typed genotypes, 68 contacts had T/T genotype and only 4 T/C genotypes, while in multibacillary (MB) group only 1 T/C genotype was found and none in paucibacillary (PB) (P> 0.05). We conclude that there is no association between the TLR2 SNP rs3804100 and leprosy in the Par� population, which still indicates the need for new immunogenetic studies with other genes involved in the immune response and a greater number of polymorphisms.

Lupus eritematoso cutáneo y lupus eritematoso sistémico: revisión de una historia sin fin / Cutaneous lupus erythematosus and systemic lupus erythematosus: endless story review

l lupus eritematoso es una afección que se conoce desde antiguo, referida en especial al compromiso cutáneo, pero ha sido mejor definida desde principios del siglo XIX, constituyéndose como una enfermedad sistémica con una base autoinmune. Mecanismos patogénicos inmunogenéticos desempeñan un papel en la susceptibilidad a la enfermedad, sobre la que actuarían variaciones hormonales y factores ambientales. De esta interacción deriva la producción de múltiples anormalidades inmunológicas, cuya acción sobre los tejidos da origen a la expresión clínica de la enfermedad. La relación entre el compromiso cutáneo, en especial crónico discoide, y sistémico, ha sido un factor de polémica, importante de dilucidar por el significado terapéutico y de pronóstico para el enfermo. De esta revisión se puede concluir que las diferentes manifestaciones del lupus constituyen una misma enfermedad, pero probablemente factores etiopatogénicos genéticos, hormonales y ambientales marcan la diferencia.

Lupus erythematosus is a condition that has been known since ancient times, especially referring to skin involvement, but has been better defined since the beginning of the 19th century, constituting itself as a systemic disease with an autoimmune basis. Immunogenetic pathogenic mechanisms play a role in disease susceptibility, on which hormonal variations and environmental factors would act. From this interaction derives the production of multiple immunological abnormalities, whose action on the tissues gives rise to the clinical expression of the disease. The relationship between cutaneous involvement, especially chronic discoid, and systemic, has been a controversial factor, important to elucidate due to its therapeutic and prognostic significance for the patient. From this review it can be concluded that the different manifestations of lupus constitute the same disease, but genetics, hormonal and environmental etiopathogenic factors probably make the difference.

Polimorfismo de los antígenos leucocitarios humanos en receptores cubanos de trasplante relacionado de progenitores hematopoyéticas / Polymorphism of human leukocyte antigens in Cuban recipients of related hematopoietic stem cell transplants

Introducción: El trasplante relacionado de células progenitoras hematopoyéticas (TCPH) es una alternativa terapéutica curativa para los pacientes con ciertos tipos de hemopatías o de inmunodeficiencias, en la que se selecciona como donante a un familiar del receptor. Objetivo: Caracterizar el sistema de antígenos leucocitarios humanos (HLA) en receptores de TCPH relacionado. Métodos: Se realizó un estudio descriptivo y transversal en el departamento de Histocompatibilidad del Instituto de Hematología e Inmunología desde enero 2013 hasta diciembre de 2015. Se tipificaron 75 genes HLA mediante la técnica de reacción en cadena de la polimerasa con cebadores de secuencia específico, de baja resolución a 117 pacientes con criterio de TCPH. Para el análisis inmunogenético se empleó el programa Arlequín 3.5.2.2. Resultados: Fueron más frecuentes los genes HLA-A*02, HLA-B*35, HLA-DQB1*03, HLA-DRB1*03 y HLA-DRB1*04, los haplotipos de dos loci HLA-A*02 B*35, HLA-DQB1*03 DRB1*04 y el haplotipo extendido HLA-A*03 B*07 DQB1*06 DRB1*15. Conclusiones: Los genes del sistema HLA en pacientes cubanos candidatos a TCPH relacionado presentaron frecuencias similares a las descritas en poblaciones generales de Cuba y el mundo, aunque con características distintivas en algunos genes y haplotipos(AU)

Introduction: Related hematopoietic progenitor cell (TCPH) transplantation is a curative therapeutic alternative for patients with certain types of hemopathies or immunodeficiencies, in which a recipient family member is selected as a donor. Objective: To characterize the human leukocyte antigen (HLA) system in related TCPH receptors. Methods: A descriptive and cross-sectional study was conducted in the Histocompatibility department of the Institute of Hematology and Immunology from January 2013 to December 2015. 75 HLA genes were typed using the polymerase chain reaction technique with specific sequence primers, from Low resolution to 117 patients with TCPH criteria. For the immunogenetic analysis, the Harlequin 3.5.2.2 program was used. Results: The genes HLA-A * 02, HLA-B * 35, HLA-DQB1 * 03, HLA-DRB1 * 03 and HLA-DRB1 * 04, the haplotypes of two HLA-A * 02 B * 35 loci were more frequent , HLA-DQB1 * 03 DRB1 * 04 and the extended haplotype HLA-A * 03 B * 07 DQB1 * 06 DRB1 * 15. Conclusions: The genes of the HLA system in Cuban patients related to TCPH presented frequencies similar to those described in general populations of Cuba and the world, although with distinctive characteristics in some genes and haplotypes(AU)

HLA-alleles class I and II associated with genetic susceptibility to neuromyelitis optica in Brazilian patients / Alelos HLA classes I e II associados à suscetibilidade genética a neuromielite óptica em pacientes brasileiros

ABSTRACT Objective: To study the genetic susceptibility to neuromyelitis optica (NMO) as well as the relationship between HLA genotypes and susceptibility to the disease in the southern Brazilian population. Methods: We analyzed patients with NMO, who met criteria for Wingerchuk's diagnosis of NMO, with detected serum anti-AQP4-IgG antibody. The HLA genotyping was performed by high-resolution techniques (Sanger sequencing) in patients and controls. The HLA genotypes were statistically compared with a paired control population. Results: The HLA genotyping revealed the diversity of the southern Brazilian population whose HLA profile resembled European and Asian populations. Some alleles had statistical correlations with a positive association (increased susceptibility) with NMO, particularly the HLA-DRB1*04:05 and *16:02. Conclusions: In our study, the HLA genotype was different to that previously reported for other Brazilian populations. Although our study had a small cohort, HLA genotypes were associated with increased susceptibility to NMO for HLA-DRB1*04:05 and *16:02. The alleles of HLA class I HLA-A*02:08 and *30:09, HLA-B*08:04 and *35:04 showed an association before the Bonferroni correction.

RESUMO Objetivo: Estudar a suscetibilidade genética a neuromielite óptica (NMO) assim como sua relação com o genótipo HLA na população do sul do Brasil. Métodos: Nós analisamos pacientes com NMO que preenchiam os critérios diagnósticos de Wingerchuk para NMO, com presença do anticorpo anti-AQP4-IgG no soro. O genótipo HLA foi realizado usando técnicas de alta resolução (sequenciamento de Sanger) em pacientes e controles. Genótipos HLA foram estatisticamente comparados com uma população controle pareada. Resultados: Genotipagem HLA revelou a diversidade da população sul brasileira cujo perfil HLA lembra as populações europeia e asiática. Alguns alelos tiveram correlação estatística com associação positiva (suscetibilidade aumentada) com NMO, particularmente o HLA-DRB1*04:05 e *16:02. Conclusões: Em nosso estudo, o genótipo HLA foi diferente do previamente relatado em outras populações brasileiras. Embora o número de pacientes tenha sido pequeno, HLA específicos foram associados com suscetibilidade aumentada a NMO para HLA-DRB1*04:05, *16:02. Os alelos HLA classe I HLA*02:08 e *30:09, HLA-B*08:04 e *35:04 tiveram associação antes da correção de Bonferroni.

Introduction of Vaccinomics to Develop Personalized Vaccines in Light of Changes in the Usage of Hantaan Virus Vaccine (Hantavax®) in Korea / 예방의학회지

The Ministry of Food and Drug Safety of Korea made an official announcement in March 2018 that the total number of inoculations of Hantaan virus vaccine (Hantavax®) would change from 3 to 4. Some aspects of this decision remain controversial. Based on the characteristics of Hantaan virus (HTNV) and its role in the pathogenesis of hemorrhagic fever with renal syndrome, it might be difficult to develop an effective and safe HTNV vaccine through the isolate-inactivate-inject paradigm. With the development of high-throughput ‘omics’ technologies in the 21st century, vaccinomics has been introduced. While the goal of vaccinomics is to develop equations to describe and predict the immune response, it could also serve as a tool for developing new vaccine candidates and individualized approaches to vaccinology. Thus, the possibility of applying the innovative field of vaccinomics to develop a more effective and safer HTNV vaccine should be considered.

Antiretroviral therapy immunologic non-response in a Brazilian population: association study using pharmaco- and immunogenetic markers

ABSTRACT Background: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated. Objective: To identify predictive genetic markers of immune response to ART. Methods: Case-control study. Out of 176 HIV-infected patients recruited in the city of Recife, Northeast Brazil, 67 patients with no immunologic response were the cases and the remaining 109 patients who responded were the controls. A set of 94 selected single nucleotide polymorphisms (SNPs) involved in antiretroviral drugs pharmacodynamic pathways and immune system homeostasis were genotyped, while the remaining 48 were ancestry informative markers (AIMs) for controlling for eventual hidden population structure. Results: Male patients were overrepresented in non-responder group (p = 0.01). Non-responders also started with lower absolute CD4+ T cell counts (p < 0.001). We found five SNPs significantly associated with the outcome, being three more frequent in non-responders than responders: rs2243250 (IL4) A allele (p = 0.04), rs1128503 (ABCB1) A allele (p = 0.03) and rs707265 (CYP2B6) A allele (p = 0.02), whereas the other two were less frequent in non-responders: rs2069762 (IL2) C allele (p = 0.004) and rs4646437 (CYP3A4) A allele (p = 0.04). Conclusion: Some significant univariate associations remained independently associated at multivariate survival analysis modeling, such as pre-treatment CD4+ T cells counts, IL2 and ABCB1 genotypes, and use of protease inhibitors, yielding a predictive model for the probability for immune response. More studies are needed to unravel the genetic basis of ART immunological non-response.

Toxoplasmosis ocular en Colombia: 10 años de aportes investigativos / Ocular toxoplasmosis in Colombia: 10 years of research contributions

Objetivo: Describir aportes investigativos en Toxoplasmosis ocular, realizados en Colombia. Método: Revisión narrativa de la literatura entre 2007 y 2017 en Toxoplasmosis Ocular (TO) en Colombia, sobre aspectos relacionados con el parásito y con el hospedero. Se incluyeron las revisiones publicadas, así como todos los artículos originales relacionados con diversos temas: epidemiológicos, inmunológicos, clínicos, diagnósticos y terapéuticos a través de PubMed usando los términos MeSH, con la siguiente sintaxis: "(((Colombia[Affiliation]) OR colombia[MeSHTerms]) OR south america[MeSH Terms]) AND "toxoplasmosis, ocular"[MeSH Terms] AND ("2007/01/01"[PDAT] : "2017/12/31"[PDAT]). Adicionalmente se realizaron búsquedas manuales. Resultados: En la búsqueda de la literatura con los términos MESH mencionados, se encontraron 36 artículos, distribuidos en el territorio con 10 en Colombia y 26 en el resto de Suramérica. Se encontraron diferencias importantes relacionadas con el parásito y con el hospedero, al comparar Colombia con el mundo. Las cepas en Colombia son más virulentas (Tipo I/III y atípicas). Se encontró una alta prevalencia de títulos positivos y desarrollo de TO en el país, presentándose el agua y los productos cárnicos como uno de los principales medios de contagio. Se determinó la importancia de péptidos que activan la respuesta inmune humoral en pacientes. Se encontraron diferencias significativas en la severidad clínica (tamaño de las lesiones, grado de inflamación, compromiso macular, compromiso bilateral y recurrencias, siendo mayores para los pacientes colombianos) relacionada con la respuesta inflamatoria producida en el hospedero, asociada con una disminución de los niveles intraoculares de IFN-γ /IL-17 y un aumento de IL-6/Il-13. En los pacientes colombianos el citoquinoma ocular está relacionado con las características clínicas, presentando una respuestaTh 2 relacionada con un compromiso severo ocular. Conclusión: Los aportes investigativos que Colombia ha realizado en TO, han sido de importancia mundial, permitiendo conocer más acerca del tipo de parásito, la epidemiología, la presentación clínica y la respuesta inmune.

Purpose: To describe research contributions in ocular toxoplasmosis performed in Colombia. Method: We conducted a narrative review of the literature on ocular toxoplasmosis (OT) in Colombia between 2007 and 2017 on aspects related to the parasite and to the host. Published reviews were included, as well as all the original articles related to various topics: epidemiological, immunological, clinical, diagnostic and therapeutic through PubMed using the MeSH terms, with the following syntax: "(((Colombia [Affi liation]) OR colombia [MeSH Terms]) OR south america [MeSH Terms]) AND "toxoplasmosis, ocular" [MeSH Terms] AND ("2007/01/01" [PDAT]: "2017/12/31" [PDAT]). Hand searches were also conducted. Results: In the literature search with the MESH terms, 36 articles were found, distributed in the territory with 10 in Colombia and 26 in the rest of South America. Important diff erences were found in the relationship between the parasite and the host when comparing Colombia with the rest of the world. The strains in Colombia are more virulent (Type I / III and atypical) and we found a high prevalence of positive titers and development of OT in the country, with water and meat products as one of the main means of contagion. The importance of peptides that triggered the humoral immune response in patients was determined. Significant differences were found in the clinical severity (with Colombian patients experiencing a greater size of lesions, degree of infl ammation, macular involvement, bilateral involvement, and recurrences) related to the infl ammatory response produced in the host, associated with a decrease in intraocular levels of IFN-γ / IL-17 and an increase of IL-6 / Il-13. In Colombian patients, ocular cytokinome is related to clinical features, presenting a Th 2 response related to severe ocular involvement. Conclusion: Research contributions of OT in Colombia have been of global importance, allowing to know more about the type of parasite, the epidemiology, the clinical presentation, the immune response.

Fc gamma receptor IIIa polymorphism is not associated with susceptibility to systemic lupus erythematosus in Brazilian patients / Polimorfismo do receptor Fc gama IIIa não está associado à susceptibilidade ao lúpus eritematoso sistêmico em pacientes brasileiros

ABSTRACT We evaluated the possible association between FCGR3A V/F (158) polymorphism and SLE susceptibility and clinical phenotype in 305 sequentially retrieved SLE patients and 300 healthy controls from the southeastern part of Brazil by allele-specific polymerase chain reaction. Our results showed no association between FCGR3A 158V/F alleles and susceptibility to SLE in this series of patients albeit the heterozygous genotype was strongly associated with the disease.

RESUMO Avaliou-se a possível associação entre o polimorfismo FCGR3A V/F (158) e a suscetibilidade e o fenótipo clínico do lúpus eritematoso sistêmico (LES) em 305 pacientes com LES admitidos sequencialmente e 300 controles saudáveis da Região Sudeste do Brasil por reação em cadeia da polimerase alelo-específica. Os resultados do presente estudo mostraram não haver associação entre os alelos FCGR3A 158 V/F e a suscetibilidade ao LES nessa série de pacientes, ainda que o genótipo heterozigoto tenha sido fortemente associado à doença.

The immunogenetics of multiple sclerosis. The frequency of HLA-alleles class 1 and 2 is lower in Southern Brazil than in the European population / Imunogenética na esclerose múltipla. A frequência dos alelos HLA classe 1 e 2 no sul do Brasil são menores que da população Europeia

ABSTRACT Objective To study the HLA of class 1and 2 in a multiple sclerosis (MS) population to verify the susceptibility for the disease in the Southern Brazil. Methods We analyzed patients with MS and controls, by direct sequencing of the genes related to HLA DRB1, DQB1, DPB1, A, B and C alleles with high resolution techniques. Results We found a lower frequency of all HLA alleles class 1 and 2 in MS and controls comparing to the European population. Several alleles had statistical correlation, but after Bonferroni correction, the only allele with significance was the HLA-DQB1*02:03, which has a positive association with MS. Conclusions Our data have different frequency of HLA-alleles than the previous published papers in the Southeast Brazil and European population, possible due to several ethnic backgrounds.

RESUMO Objetivo Estudo do HLA classes 1 e 2 em pacientes com esclerose múltipla (EM) a fim de verificar a susceptibilidade para a doença em uma população do Sul do Brasil. Métodos Foram analisados por sequenciamento direto de alta resolução os genes relacionados com os HLA DRB1, DQB1, DPB1, A, B e C em casos de EM comparados com uma população controle normal. Resultados Foi encontrado uma frequência menor dos alelos dos HLA classe 1 e 2 nos casos de EM e controles quando comparado com a população Europeia. Diversos alelos mostraram correlação estatística, mas depois da correção de Bonferroni, somente o alelo do HLA-DQB1*02:03 foi positivo para a EM. Conclusões Encontramos frequência diferente dos alelos do HLA relatados previamente nos Sudeste do Brasil e Europeus, possivelmente devido a origem étnica diferente da população estuda.

Elementos clave de la inmunogenética de la psoriasis: A review / Key elements of psoriasis immunogenetics / Elementos importantes da imunogenética da psoríase

La psoriasis, que afecta de 2% a 3% de la población mundial, es una de las enfermedades cutáneas más frecuentes, Se presenta en cualquier etapa de la vida. La psoriasis tipo I o temprana comienza antes de los 40 años en tanto que la tipo II es de inicio tardío, luego de los 40 años. Tiene una fuerte base genética y la probabilidad de heredarla cuando los dos padres están afectados es hasta del 50%. Se han descrito diferentes regiones de susceptibilidad asociadas a la psoriasis, que se denominan PSORS, de las que PSORS-1 es la más frecuente. PSORS-1 está en el cromosoma 6 en el que se localiza el HLA-Cw6, que es el gen hasta ahora más relacionado con la psoriasis. La función de HLA-Cw6 en la psoriasis no está completamente entendida, pero se ha asociado con la psoriasis tipo I, la psoriasis en gotas y la presentación antigénica de una gama de antígenos entre los que se encuentran los derivados de Streptococcus pyogenes. Por otra parte, algunos polimorfismos de nucleótido simple en genes que codifican para citocinas como IL-12, IL-23, TNF-α o sus receptores, se han relacionado con la inmunopatogénesis de esta enfermedad.

Psoriasis is one of the most common skin diseases, affecting 2% to 3% of the world population. It occurs at any stage of life. ''Early'' psoriasis or type I manifests before 40 years, and ''late'' psoriasis or type II, after 40 years. It has a strong genetic basis and the probability of inheriting the disease when both parents are affected is up to 50%. Different susceptibility regions associated with psoriasis, called PSORS, have been described, PSORS-1 being the most frequent one. It is in chromosome 6 and in this region HLA-Cw6 is located, which is until now the gene more associated with psoriasis. The role of HLA-Cw6 in psoriasis is not fully understood, but it has a relationship with type I psoriasis, guttate psoriasis and the presentation of an array of antigens including those derived from Streptococcus pyogenes. Furthermore, some single nucleotide polymorphisms in genes encoding cytokines such as IL-12, IL-23, TNF-α or their receptors are associated with the immunopathogenesis of the disease.

A psoríase, que afeta de 2% a 3% da população mundial, é uma das doenças cutâneas mais frequentes, Apresenta-se em qualquer etapa da vida. A psoríase tipo I ou precoce começa antes dos 40 anos enquanto a tipo II é de início tardio, depois dos 40 anos. Tem uma forte base genética e a probabilidade de herdá-la quando os dois pais estão afetados é até de 50%. Descreveram-se diferentes regiões de susceptibilidade associadas à psoríase, que se denominam PSORS, das que PSORS-1 é a mais frequente. PSORS-1 está no cromossomo 6 no que se localiza o HLA-Cw6, que é o gene até agora mais relacionado com a psoríase. A função de HLA-Cw6 na psoríase não está completamente entendida, mas se associou com a psoríase tipo I, a psoríase em gotas e a apresentação antigénica de uma gama de antígenos entre os que se encontram os derivados de Streptococcus pyogenes. Por outra parte, alguns polimorfismos de nucleótido simples em genes que codificam para citocinas como IL-12, IL-23, TNF-α ou seus receptores, relacionaram-se com a imunopatogênese desta doença.

Contribuicao das moleculas de antigeno de histocompatibilidade leucocitaria (HLA) para a contratura de Dupuytren em uma populacao do Sudeste do Brasil / The contribution of HLA molecules to Dupuytren's contracture in a Southeast Brazilian population

Objetivo: O objetivo deste estudo foi investigar o fenótipo do HLA em pacientes com contratura de Dupuytren (CD) para verificar a correlação desses alelos com os fatores de risco para o desenvolvimento da CD na população brasileira. Métodos: Este foi um estudo de caso-controle de 25 pacientes com CD e 443 indivíduos saudáveis sem histórico de doenças associadas ao HLA. As tipagens classe I e classe II do HLA foram feitas utilizando o método iniciador de sequências específicas da reação em cadeia da polimerase. Resultados: O fenótipo HLA-B*18 foi observado em 32% dos pacientes e 10,5% do grupo controle. Contudo, os valores de p não permaneceram significativos após correção. Discussão: Apesar de termos observado um aumento na tendência de os pacientes com CD terem o alelo HLA-B*18, os resultados não foram estatisticamente significativos após correção. Esse alelo foi maior em pacientes de etnia italiana e/ou espanhola, locais com frequências superiores a 18% e 14%, respectivamente. São necessárias investigações adicionais com uma coorte maior de pacientes com CD para confirmar o possível papel do HLA nessa doença. .

Purpose: The aim of the present study was to investigate the HLA phenotype in Dupuytren's contracture (DC) patients in order to verify the correlation of these alleles with risk factors for development of DC in the Brazilian population. Methods: This was a case-controlled study of 25 DC patients and 443 healthy individuals with no history of HLA-associated diseases. HLA class I and class II typing was performed using the polymerase chain reaction sequence-specific primer method. Results: The HLAB*18 phenotype was observed in 32% of the patients and 10.5% of controls. However, P values did not remain significant after correction. Discussion: Although we observed an increased tendency of DC patients to possess the HLA-B*18 allele, the results were not statistically significant after correction. This allele was higher in patients of Italian and/or Spanish ethnicity, localities with frequencies higher than 18.0% and 14.0% respectively. Further investigation with a larger cohort of DC patients is required to confirm the potential role of HLA in this disease. .

Role of hepatitis B virus mutation, somatic mutations of hosts and related immune genetics in liver cirrhosis and hepatocellular carcinoma / 第二军医大学学报

Hepatitis B virus (HBV) infection has always been one of the most important public health issues in mainland China, causing a huge disease burden. It often takes decades for the chronic process of malignant transformation from HBV infection to different stages of liver diseases. Mutations associated with virus survival are eventually selected by the chronic infection process and under the immune pressure of host. These selected HBV mutations further promote the malignant transformation of liver diseases. A large amount of somatic mutations are produced in the HBV-related chronic inflammatory micro-environment, and those survival-related mutations will then be selected. The selected HBV mutations and host somatic mutations work together to promote the malignant transformation, which can be termed as an evolutionary process of “mutation-selection-adaptation”. In addition, genetic variations of individual hosts also play an important role in HBV related disease progression. For example, single-nucleotide polymorphisms of STAT pathway and HLA can interact with important HBV mutations and therefore affect HBV-related disease progression.

Ontotransplante: ontologia relacionada à histocompatibilidade / Ontotransplante: ontology related to histocompatibility / Ontotransplante: ontología relacionada a la histocompatibilidad

Objetivo: Apresentar a Ontotransplante, uma ontologia para a representação do conhecimento utilizado em laboratórios de Histocompatibilidade para transplante de órgãos e o Complexo Principal de Histocompatibilidade. Método: Pesquisa descritiva documental e de desenvolvimento, cujos passos metodológicos consistiram em determinar o domínio e o escopo da ontologia, avaliar a possibilidade de reuso, enumerar termos importantes, organizar a hierarquia das classes, criar propriedades e validar os termos. Resultados: A ontologia possui 329 termos e foi elaborada com base na 4º. Edição do Manual Laboratorial da Sociedade Americana de Histocompatibilidade e Imunogenética. Conclusão: No transplante de órgãos, a certeza do uso correto de um determinado termo reduz o tempo e contribui para o correto diagnóstico dos exames realizados. Esta ontologia é um primeiro passo em direção à padronização de terminologia da área.

Objective: To present the Ontotransplante, an ontology for knowledge representation used in histocompatibility laboratories for organ transplants and the Major Histocompatibility Complex. Method: Descriptive, documentary and development research, whose methodological steps were to determine the domain and scope of the ontology, evaluate the possibility of reuse, enumerate important terms, organize the hierarchy of classes, create properties and validate terms. Results: The ontology has 329 terms and was prepared based on the 4th Ed. The American Society for Histocompatibility and Immunogenetics Manual. Conclusion: In organ transplantation, the certainty of the correct use of a particular term reduces the time and contributes to the correct diagnosis of the tests. This ontology is a first step toward the standardization of the terminology in the area.

Objetivo: Presentar el Ontotransplante, una ontología para la representación del conocimiento utilizado en laboratorios de Histocompatibilidad para trasplante de órganos y el Complejo Principal de Histocompatibilidad. Método: Investigación descriptiva documental y de desarrollo, cuyos pasos metodológicos consistieron en determinar el dominio y o alcance de la ontología, evaluar la posibilidad de reutilización, enumerar términos importantes, organizar la jerarquía de las clases, crear propiedades y validar los términos. Resultados: La ontología posee 329 términos y fue elaborada con base en la 4º. Edición del Manual del Laboratorio de la Sociedad Americana de Histocompatibilidad e Inmunogenética. Conclusión: En el trasplante de órganos, la certeza del uso correcto de un determinado término reduce el tiempo y contribuye para el correcto diagnóstico de los exámenes realizados. Esta ontología es un primer paso en dirección a la estandarización de terminología del área.

Avaliação da presença de mutações de resistência no gene da NS5B e do prognóstico da infecção pelo HCV através da IL-28B em pacientes monoinfectados com HCV no RJ / Evaluation of resistance mutations presence in the NS5B gene and prognosis of HCV infection throught IL-28B in HCV monoinfected patients of RJ

Estima-se que a prevalência global da população mundial com hepatite C é de 3%. Pouco se sabe sobre a resposta ao tratamento com respeito à resistência viral. Algumas mutações no fragmento de 109 aminoácidos da NS5B são associadas com resistência ao interferon (IFN) e ribavirina (RBV). Estudos moleculares e clínicos identificaram fatores associados com o hospedeiro e vírus relacionados associada com a resposta ao tratamento, tal como o gene que codifica a IL-28B. Este estudo foi dividido em duas fases, cujos objetivos foram caracterizar a frequência de mutações que conferem resistência ao HCV e avaliar a relevância das mutações em pacientes Respondedores (R) ou Não Respondedores (NR) ao tratamento e caracterizar geneticamente as populações sobre polimorfismos genéticos nos SNPs da IL-28B em relação ao prognóstico da resposta ao tratamento. As amostras dos pacientes foram submetidas a testes de genotipagem e carga viral. As sequências geradas foram comparadas no BLAST e no banco de dados Los Alamos HCV. Realizamos o alinhamento das sequências homólogas e as mutações identificadas. Com base no genótipo e carga viral determinamos a classificação dos pacientes de acordo com a resposta à terapia. O DNA genômico foi isolado a partir de sangue periférico para a realização da tipagem de SNPs de IL-28B. A metodologia utilizada foi de PCR em tempo real utilizando sondas TaqMan SNP específico. A análise dos dados foi realizada utilizando GraphPad Prism com qui-quadrado, risco relativo (RR), Odds Ratio (OR) e intervalo de confiança de 95%, com um nível de significância de P <0,05. Foi encontrado na primeira fase deste estudo uma taxa significativa mutações associadas ao tratamento nas amostras estudadas. A prevalência de mutações associadas à resistência ao IFN e RBV bem como a novos medicamentos antivirais localizados no fragmento de 109 aminoácidos da NS5B foi examinado em 69 indivíduos infectados naïve no Rio de Janeiro, Brasil. Na segunda fase, as mutações foram ...

It is estimated that the overall prevalence of the average world population with hepatitis C is 3%. Little is known about the treatment response with respect to viral resistance. Some mutations in the 109-aminoacid fragment of NS5B are associated to Interferon (IFN) and Ribavirin (RBV) resistance. Molecular and clinical studies have identified factors associated with the host and related viruses associated with response to treatment, as the gene encoding IL-28B. This study was divided into two phases whose objectives were to characterize the frequency of mutations conferring resistance to HCV viral evaluating the relevance of these in Responders (R) or Non-Responders (NR) patients to treatment and to characterize genetically the populations regarding genetic polymorphisms SNPs IL-28B in relation to prognosis of response to treatment for HCV. Patient samples were subjected to tests for genotyping and viral load. The sequences generated were compared in the BLAST and the Los Alamos database HCV. We conducted the alignment of homologous sequences and mutations identified. Based on virological parameters genotype and viral load determined the classification of patients according to response to therapy. Genomic DNA was isolated from peripheral blood for carrying out the typing of SNPs of IL-28B. The methodology used was real-time PCR using TaqMan probes specific SNPs. Data analysis was performed using GraphPad Prism with chi-square, relative risk (RR), Odds Ratio (OR) and confidence interval of 95% with a significance level of P <0.05. To study these biological parameters we associated the responsive patients, non-responders, the viral load, genotype, and IL-28B polymorphism to treatment outcome. We found in the first phase of this study a significant rate of treatment-associated mutations in the samples studied. The prevalence of mutations associated to resistance to interferon and ribavirin (IFN/RBV) as well new antiviral drugs located in the 109 aminoacid ...

Estudo da frequência dos alelos de HLA-DRB1 em pacientes brasileiros com artrite reumatoide / Study of the frequency of HLA-DRB1 alleles in Brazilian patients with rheumatoid arthritis

Os alelos HLA-DRB1, que codificam uma sequência de aminoácidos (QKRAA/QRRAA/RRRAA) nas posições 70 a 74 da terceira região hipervariável da cadeia β1 do gene DRB1, denominada epítopo compartilhado (EC), estão associados a maior suscetibilidade e gravidade para artrite reumatoide (AR) em diversas populações. OBJETIVO: Determinar a frequência dos alelos HLA-DRB1 em pacientes brasileiros com AR, e sua associação a fator reumatoide (FR) e anticorpos antipeptídeos citrulinados (ACPA). MATERIAL E MÉTODOS: Foram incluídos 412 pacientes com AR e 215 controles. A tipificação HLA-DRB1 foi realizada pela reação em cadeia da polimerase (PCR) usando primers específicos e hibridização com oligonucleotídeos de sequência específica (SSOP). A pesquisa de ACPA foi determinada pela técnica de ELISA, e a do FR por nefelometria. Para análises estatísticas foram utilizados os testes do qui-quadrado e t de Student e a regressão logística. RESULTADOS: Alelos HLA-DRB1*04:01, *04:04 e *04:05 associaram-se à AR (P < 0,05)); a despeito do amplo intervalo de confiança, vale a pena ressaltar a associação observada entre o alelo DRB1*09:01 e a doença (P < 0,05). Alelos HLA-DRB1 EC+ foram observados em 62,8 por cento dos pacientes e em 31,1 por cento do grupo-controle (OR 3,62; P < 0,001) e estiveram associados a ACPA (OR 2,03; P < 0,001). Alelos DRB1-DERAA mostraram efeito protetor para AR (OR 0,42; P < 0,001). CONCLUSÃO: Em uma amostra de pacientes brasileiros com AR de etnia majoritariamente mestiça, alelos HLA-DRB1 EC+ estiveram associados à suscetibilidade à doença e à presença de ACPA.

The HLA-DRB1 alleles encoding an amino acid sequence (QKRAA/QRRAA/RRRAA) at position 70 74 of the third hypervariable region of the β1 chain of the HLA-DRB1 gene, called shared epitope (SE), are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in different populations. OBJECTIVE: To determine the frequency of HLA-DRB1 alleles in Brazilian patients with RA and their association with rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA). METHODS: Four hundred and twelve patients with RA (ACR 1987) and 215 controls were included. HLA-DRB1 typing was performed by use of polymerase chain reaction (PCR) with specific primers and hybridization with sequence-specific oligonucleotide probe (SSOP). ACPA was measured by use of the ELISA technique and RF by nephelometry. The statistical analysis comprised the chi-square and Student t tests and logistic regression. RESULTS: HLA-DRB1*04:01, *04:04, *04:05 alleles were associated with RA (P < 0.05); despite the wide confidence interval, it is worth noting the association between the DRB1*09:01 allele and RA (P < 0.05). HLA-DRB1 SE+ alleles were observed in 62.8 percent of the patients and in 31.1 percent of controls (OR 3.62; P < 0.001) and were associated with ACPA (OR 2.03; P < 0.001). DRB1-DERAA alleles showed a protective effect against RA (OR 0.42; P < 0.001). CONCLUSION: In a sample of Brazilian patients with RA, most of whom of mixed heritage, HLA-DRB1 SE+ alleles were associated with susceptibility to disease and presence of ACPA.

Interleukin-10 but not interleukin-18 may be associated with the immune response against well-differentiated thyroid cancer

OBJECTIVES: The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis. METHODS: We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10 ± 68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism. RESULTS: Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74 percent of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto's thyroiditis who had received a lower 131I cumulative dose and did not present lymph node metastases. CONCLUSIONS: We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients, and this autoimmunity may favor a better prognosis for these patients.

Polimorfismos dos genes HLA e regiões promotoras do TNF-'alfa'-238 e -308 como fatores de sucetibilidade a psoriase e gravidade da doença / HLA and TNF-Alpha promoter regions -238 and -308 polymorphisms and marks of susceptibility to psoriasis and severety of the disease

Psoríase é uma dermatose inflamatória crônica, determinada por desregulação do sistema imune e associada a várias comorbidades. O marcador genético mais associado à psoríase em todas as populações é o HLA-CW06. Polimorfismos na região promotora do TNF-a, especialmente a troca de uma guanina por uma adenina nas posições -238 e -308 estão relacionados à alta produção de TNF-a e risco aumentado para psoríase nas populações caucasóides e não em asiáticos. Com o objetivo de determinar se polimorfismos destes genes podem ser fatores de risco para susceptibilidade ou gravidade da doença em pacientes brasileiros, foi realizado um estudo caso-controle com 69 pacientes com psoríase de início até 40 anos, com acompanhamento por dez anos para caracterização de sua evolução clínica em doença leve (grupo I) e grave (grupo II), e 70 indivíduos sadios. Foi feita a identificação dos alelos HLA classe I e II e SNPs da região promotora do TNF-a -238 e -308. Coletaram-se 10 mL de sangue periférico dos indivíduos e se realizou a extração do DNA através do método salting out. O DNA foi amplificado pela reação em cadeia da polimerase (PCR), com primers sequência-específica. As freqüências alélicas e gênicas foram estimadas por contagem direta e a comparação entre as frequências dos grupos foi efetuada por Teste de Fisher (programa GraphPad InStat 3.05). Dois métodos computacionais foram usados...

Psoriasis is an erythematous, scaly inflammatory dermatosis with a complex immunologic basis. The strongest genetic marker for psoriasis is HLA-Cw*06. Polymorphisms in the TNF-a promoter region, especially replacement of guanine with adenine in positions -238 and -308 are related to higher TNF-a production and higher risk for psoriasis in Caucasoid populations, not found in Asians. We did a case-control study of 69 patients with psoriasis type I and 70 controls, characterized clinical progression along 10-years of follow-up in mild or severe disease and determined HLA class I, II and TNF-a SNPs -238 and -308 polymorphisms to demonstrate whether these polymorphisms may be genetic risk for susceptibility to psoriasis or severity of the disease in Brazilians. Peripheral blood (10 ml) was collected. Genomic DNA from both psoriasis patients and controls was isolated using a salting out procedure. Polymorphisms were identified by PCR/SSP. Alleles and genotypes frequencies were compared by Fisher's test (GraphPad InStat 3.05 software). Two computational methods were used to determine the haplotypes of each subject, without taking into account any prior information: (1) the ELB algorithm implemented by the ARLEQUIN 3.1 software and (2) a coalescence based method as...

Caracterização de polimorfismos em genes associados à imunopatogênese da infecção pelo Mycobacterium tuberculosis / Characterization of polymorphisms in genes associated with the immunopathogenesis of Mycobacterium tuberculosis infection

A tuberculose (TB) é a principal causa de morbi-mortalidade por doença infecciosa no mundo. A cada ano ocorrem cerca de 9 milhões de novos casos com aproximadamente 2 milhões de mortes, sendo que, somente 1 em cada 10 indivíduos desenvolvem a doença. Fatores genéticos do hospedeiro podem influenciar no controle da susceptibilidade à doença. Desta forma, este trabalho teve como objetivo a caracterização de polimorfismos genéticos associados à imunopatogênese da TB. Para tanto, foram incluídos 172 pacientes com TB pulmonar ativa e 173 indivíduos controle sadios. Foi realizada a extração de DNA em todos os participantes deste estudo e os polimorfismos foram caracterizados para: NOS2A (-954G-C), IFNG (+874T-A), receptor de vitamina D (VDR) (TaqI, FokI, BsmI e ApaI) e proteína transportadora da vitamina D (DBP) (HaeIII e StyI). Não foi possível determinar nenhuma associação com o desenvolvimento da TB em relação aos polimortismos genéticos descritos neste estudo...

No entanto, quando ajustamos a casuística em relação ao sexo e raça podemos verificar que o polimorfismo no gene VDR determinado pela enzima de restrição TaqI foi associado com o desenvolvimento da TB em nossa população. Apesar de não observarmos significância estatística em relação aos outros polimorfismos deste gene VDR (FokI, BsmI e ApaI), foi possível obervar que cinco das dezesseis possíveis combinações genéticas foram consideradas raras, sendo seis delas encontrados em cerca de 74,8 por cento, tanto nos pacientes com TB quanto nos indivíduos controle. Apesar de não terem sido observadas diferenças estatísticas nos polimorfismos dos genes avaliados neste estudo, estes devem ser considerados de extrema importância na compreensão da ação do sistema imune bem como a expressão de seus produtos no desenvolvimento da TB, em células infectadas ou não pelo Mtb. Desta forma, análises funcionais em relação a estes genes e seus produtos estão em andamento para tentarmos esclarecer esta associação e possivelmente assegurar seu papel no desenvolvimento da tuberculose em nossa população...

Advance in Research of Immunogenetics of Multiple Sclerosis(review) / 中国康复理论与实践

@#The etiology and occurred mechanism of multiple sclerosis are remain unclear. The authors review the advance in research of heredity epidemiology, molecular biology, genomic screen and heredity factors of multiple sclerosis.