Niveles glutatión reducido y estado redox celular en pacientes pediátricos con inmunodeficiencias / Reduced glutathione levels and cellular redox status in pediatric patients with immunodeficiencies

Introducción: Las alteraciones en el estado redox celular se han descrito como factores causales en diversas enfermedades. La depleción del glutatión reducido se ha asociado fundamentalmente a enfermedades neurodegenerativas, pulmonares, hepáticas, cardiovasculares e inmunológicas. Objetivo: Determinar las concentraciones de glutatión reducido y el estado redox celular en pacientes pediátricos con inmunodeficiencias. Métodos: Se estudiaron 21 pacientes con inmunodeficiencias procedentes de la consulta de Inmunogenética, en edades comprendidas entre 1 y 8 años, de ambos sexos, y 8 niños en el mismo rango de edad de los pacientes, como grupo control, con estudios de inmunidad humoral y celular normales. Los pacientes con diagnóstico de inmunodeficiencia se dividieron para su estudio en 2 grupos según el componente afectado de la respuesta inmune: humoral y celular. Fueron determinadas las concentraciones intraeritrocitarias de glutatión reducido y oxidado, mediante un método de HPLC-UV. Para evaluar el estado redox celular se calculó la relación entre las formas reducidas y oxidadas del glutatión (GSH/GSSG). Resultados: Las concentraciones de glutatión reducido y el estado redox celular se encontraron disminuidos en ambos grupos de pacientes en relación con los niños sin inmunodeficiencia (p=0,031 y p=0,03; respectivamente). El glutatión oxidado no mostró diferencias entre los grupos. Conclusiones: En los pacientes con inmunodeficiencia se evidenció la afectación del estado redox celular como consecuencia de la disminución del glutatión reducido. Este primer acercamiento ofreció las potencialidades del empleo de estos biomarcadores en la evaluación integral de pacientes con inmunodeficiencia(AU)

Introduction: Alterations in the cellular redox state have been described as causal factors in various diseases. Reduced glutathione depletion has been fundamentally associated with neurodegenerative, pulmonary, liver, cardiovascular and immunological diseases. Objective: To determine the concentrations of reduced glutathione and the cellular redox status in pediatric patients with immunodeficiencies. Methods: We studied 21 patients with immunodeficiencies from the immunogenetic service, aged between 1 and 8 years and as a control group, 8 children in the same age range as the patients, with normal humoral and cellular immunity studies. Patients diagnosed with immunodeficiency were divided into two groups according to the affected component of the immune response: humoral and cellular. The intraerythrocyte concentrations of oxidized and reduced glutathione were determined by means of an HPLC-UV method. To evaluate the cellular redox state, the relationship between the reduced and oxidized forms of glutathione (GSH/GSSG) was calculated. Results: Reduced glutathione concentrations and cellular redox status were found to be decreased in both groups of patients in relation to children without immunodeficiency (p=0,031 and p=0,03; respectively). Oxidized glutathione showed no difference between the groups. Conclusions: In patients with immunodeficiency, the cellular redox state is affected as a consequence of the decrease in reduced glutathione. This first approach offers the potential for the use of these biomarkers in the comprehensive evaluation of patients with immunodeficiency(AU)

Inmunodeficiencias primarias: un reto para la inmunogenética / Primary immunodeficiencies: a challenge for immuno-genetics

Las inmunodeficiencias primarias constituyen un grupo de más de 300 enfermedades frecuentemente graves y a menudo mortales que reflejan un déficit cuantitativo o cualitativo en uno o más componentes del sistema inmunitario. Son el resultado de defectos genéticos heredados que suelen afectar a 1 de cada 8000 a 10 000 nacidos vivos. Las manifestaciones clínicas suelen ser muy variadas, debido a que en su mayoría presentan una amplia heterogeneidad genética: infecciones (comunes recurrentes, comunes graves, o raras y graves), inflamación, autoinmunidad, malignidad o alergia. Teniendo en cuenta que a los profesionales médicos de diversas especialidades les resulta difícil identificar cuándo están en presencia de una IDP, nos proponemos describir las características clínicas, epidemiológicas, inmunitarias y genéticas de las inmunodeficiencias primarias. Para la realización de la revisión bibliográfica se utilizaron 27 referencias bibliográficas(AU)

Primary immunodeficiencies constitute a group of more than 300 frequently serious and often fatal diseases that reflect a quantitative and / or qualitative deficit in one or more components of the immune system. They are the result of inherited genetic defects that usually affect 1 in 8,000 to 10,000 live births. The clinical manifestations are usually very varied, because they mostly have a wide genetic heterogeneity, they can be caused by infections (common recurring, common serious, or rare and serious), inflammation, autoimmunity, malignancy, or allergy. Given that medical professionals of various specialties find it difficult to identify when they are in the presence of an primary immunodeficiency, it is proposed as an objective: to describe the clinical, epidemiological, immunological and genetic characteristics of Primary immunodeficiency. For the literature review, 27 bibliographic references were used(AU)

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.

Cystic Degeneration of Hepatocellular Carcinoma Mimicking Mucinous Cystic Neoplasm / 대한소화기학회지

Spontaneous regression of tumors is an extremely rare event in hepatocellular carcinoma (HCC) with only a few reports available. With the accumulation of clinical information and tumor immunogenetics, several mechanisms for the cystic changes of HCC have been suggested, including arterial thrombosis, inflammation, and rapid tumor growth. This paper reports an uncommon case of the partial regression of HCC, which was initially misdiagnosed as a mucinous cystic neoplasm of the liver due to the unusual radiologic findings. A 78-year-old female with the hepatitis B virus and liver cirrhosis presented with an approximately 5 cm-sized cystic mass of the liver. From the radiologic evidence of a papillary-like projection from the cyst wall toward the inner side, the initial impression was a mucinous cystic neoplasm of the liver. The patient underwent a surgical resection and finally, cystic degeneration of HCC, in which approximately 80% necrosis was noted. This case suggests that if a cystic neoplasm of liver appears in a patient with a high risk of HCC on a hepatobiliary imaging study, it is prudent to consider the cystic degeneration of HCC in a differential diagnosis.

Cystic Degeneration of Hepatocellular Carcinoma Mimicking Mucinous Cystic Neoplasm / 대한소화기병학회잡지

Spontaneous regression of tumors is an extremely rare event in hepatocellular carcinoma (HCC) with only a few reports available. With the accumulation of clinical information and tumor immunogenetics, several mechanisms for the cystic changes of HCC have been suggested, including arterial thrombosis, inflammation, and rapid tumor growth. This paper reports an uncommon case of the partial regression of HCC, which was initially misdiagnosed as a mucinous cystic neoplasm of the liver due to the unusual radiologic findings. A 78-year-old female with the hepatitis B virus and liver cirrhosis presented with an approximately 5 cm-sized cystic mass of the liver. From the radiologic evidence of a papillary-like projection from the cyst wall toward the inner side, the initial impression was a mucinous cystic neoplasm of the liver. The patient underwent a surgical resection and finally, cystic degeneration of HCC, in which approximately 80% necrosis was noted. This case suggests that if a cystic neoplasm of liver appears in a patient with a high risk of HCC on a hepatobiliary imaging study, it is prudent to consider the cystic degeneration of HCC in a differential diagnosis.

Expressão heteróloga de proteínas do vírus da Hepatite A e avaliação da imunogenicidade / Heterologous expression of hepatitis a virus proteins and immunogenicity evaluation

O vírus da hepatite A (HAV) é o principal agente etiológico das hepatites virais agudas e estima-se que ocasione 1,5 milhão de novas infecções no mundo anualmente. Apesar da eficácia apresentada pelas vacinas comerciais, a replicação do HAV em cultura de células é lenta e apresenta baixo rendimento, o que torna a sua produção difícil e dispendiosa. Nesse contexto, o uso de proteínas recombinantes do HAV pode representar uma alternativa ao modelo de vacina existente. O presente trabalho teve como objetivo expressar e avaliar a imunogenicidade das partículas virais destituídas de ácido nucleico (VLPs) e da proteína VP1 do HAV. As VLPs foram geradas a partir do sistema baculovírus/células de inseto através da infecção de células de inseto com baculovírus recombinantes contendo as regiões P1-2A e P3 do genoma do HAV. A poliproteína P1-2A foi expressa, clivada e se organizou em estruturas que continham epitopos conformacionais de neutralização. Partículas com características similares ao HAV foram identificadas por microscopia eletrônica, sugerindo que as proteínas expressas se montaram em VLPs. Em paralelo, a VP1 foi expressa nos sistemas baculovírus/células de inseto e Escherichia coli. Níveis mais elevados de expressão foram obtidos em E. coli, o que consequentemente aumentou a taxa de recuperação da proteína purificada. A VP1 derivada de E. coli foi utilizada nos ensaios de antigenicidade e mostrou reatividade frente aos soros de pacientes infectados pelo HAV, o que demonstra seu potencial como um marcador para diagnóstico. Para os estudos de imunogenicidade, a VP1 derivada de E. coli foi combinada a dois adjuvantes, o hidróxido de alumínio (Al(OH)3) e o adjuvante a base de saponina...

The hepatitis A virus (HAV) is the primary etiological agent of acute viral hepatitis and it is estimated to cause 1.5 million of new infections each year worldwide. Despite the effectiveness of commercial vaccines, the replication of HAV in cell culture is slow and haslow yield, which makes it difficult and expensive to manufacture. In this context, the use of recombinant HAV proteins could represent an alternative model to the existing vaccines. This study aimed to express and evaluate the immunogenicity of virus-like-particles (VLPs) and VP1 protein of HAV. The VLPs were generated using the baculovirus/insect cell expression system by the infection of insect cells with recombinant baculovirus containing HAV P1-2A and P3 regions. The P1-2A polyprotein was successfully expressed, cleaved and organized into structures that contained neutralizing conformational epitopes. HAV-like particles were identified by electron microscopy, suggesting that the expressed proteins were assembled into VLPs. In parallel, VP1 was expressed in both baculovirus/insect cell and Escherichia coliexpression systems. Higher protein levels were obtained in E. coli, which consequently increased the recovery rate after protein purification. The E. coli-derived VP1 was then used in antigenicity assays and showed reactivity against sera from patients infected with HAV, demonstrating its potential as a diagnostic marker. For immunogenicity studies, the E. coli-derived VP1 was combined with two adjuvants, aluminum hydroxide (Al(OH)3) and the saponin-based adjuvant...

Cloning and expression of CD19, a human B-cell marker in NIH-3T3 cell line

CD19 is a pan B cell marker that is recognized as an attractive target for antibody-based therapy of B-cell disorders including autoimmune disease and hematological malignancies. The object of this study was to stably express the human CD19 antigen in the murine NIH-3T3 cell line aimed to be used as an immunogen in our future study. Total RNA was extracted from Raji cells in which high expression of CD19 was confirmed by flow cytometry. Synthesized cDNA was used for CD19 gene amplification by conventional PCR method using Pfu DNA polymerase. PCR product was ligated to pGEM-T Easy vector and ligation mixture was transformed to DH5 alpha competent bacteria. After blue/white selection, one positive white colony was subjected to plasmid extraction and direct sequencing. Then, CD19 cDNA was sub-cloned into pCMV6-Neo expression vector by double digestion using Kpnl and HindIII enzymes. NIH-3T3 mouse fibroblast cell line was subsequently transfected by the construct using Jet-PEI transfection reagent. After 48 hours, surface expression of CD19 was confirmed by flow cytometry and stably transfected cells were selected by G418 antibiotic. Amplification of CD19 cDNA gave rise to 1701 bp amplicon confirmed by alignment to reference sequence in NCBI database. Flow cytometric analysis showed successful transient and stable expression of CD19 on NIH-3T3 cells [29 and 93%, respectively]. Stable cell surface expression of human CD19 antigen in a murine NIH-3T3 cell line may develop a proper immunogene which raises specific anti-CD19 antibody production in the mice immunized sera

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.

Immunogenicity evaluation of a DNA vaccine expressing the hepatitis C virus non-structural protein 2 gene in C57BL/6 mice

Most of the hepatitis C virus [HCV] infections elicit poor immune responses and 75% to 85% of cases become chronic; therefore, the development of an effective vaccine against HCV is of paramount importance. In this study, we aimed to evaluate co-administration of HCV non-Structural Protein 2 and IL-12 DNA vaccines in C57BL/6 mice A plasmid encoding full-length HCV NS2 protein [non-structural protein 2] was generated and used to vaccinate mice. Negative control [an empty expression vector] was also employed to evaluate the background response. To investigate immune responses against vaccine, C57BL/6 mice received three doses of the vaccine with a two-week interval. Cellular immunity was assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay for lymphocyte proliferation, lactate dehydrogenase release for cytotoxic T lymphocyte [CTL] activity and cytokine assay. The findings demonstrated that immunization of mice with plasmid expressing HCV NS2 induced CTL response, interferon gamma production, and lymphocyte proliferation compared to negative control. The results also demonstrated that co-administration of IL-12 with the HCV NS2 plasmid induced significantly better immune response in C57BL/6 mice. DNA vaccine encoding HCV NS2 is an effective candidate that can trigger CTL-based immune response against HCV. In addition, the results suggested that combining the DNA vaccine approach with immune stimulatory cytokines may significantly enhance antigen-specific immune responses

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.

Immunogenicity of HLA-DR1 restricted peptides derived from leishmania major gp63 using FVB/N-DR1 transgenic mouse model

Leishmaniasis is a worldwide disease prevalent in tropical and sub- tropical countries. In the present study the immunogenicity of three human HLA-DR1 restricted peptides derived from L. major gp63 protein was evaluated using FVB/N-DR1 transgenic mouse model. The immunity generated by three MHC class II - restricted peptides with the sequence of AARLVRLAAAGAAVT [AAR], AAPLVRLAAAGAAVT [AAP] and SRYDQLVTRVVTHE [ASR] derived from L. major gp63 protein were predicted using a web-based software [SYFPEITHI] and tested in FVB/N-DR1 transgenic mice. Immunization of FVB/N-DR1 transgenic mice with one of the three predicted peptides [AAR] resulted in high levels of Th1-type immune response as well as significant levels of IFN-gamma detected by Proliferation assay and ELISA. The results indicate a high level of immunogenicity for AAR, which can be a potent candidate for peptide vaccine in Leishmania infections.

Diagnosis of canine leptospirosis using an immunomagnetic separation-PCR method

Diagnosis of leptospirosis by PCR is hampered due to the presence of substances on biological fluids. Here, we report an immunomagnetic separation step prior to PCR which improved the detection of Leptospira spp. in blood and urine samples from dogs. It resulted in a significant improvement on sensitivity for diagnosis of canine leptospirosis.

Immunogenetic diagnosis of large granular lymphocytic leukemia and therapy by sirolimus / 中国实验血液学杂志

This study was aimed to investigate the immunogenetic diagnosis of large granular lymphocytic leukemia (LGLL) and therapeutic efficacy of sirolimus, and to analysis 256 cases of LGLL reported at home and abroad within 2000 - 2010. Besides the routine examination of peripheral blood and classification of bone marrow cell morphology, the expression of T cell receptor variable region of β-chain (TCR BV), CD3, CD4 and CD8, as well as TCRαβ, TCRγδ were detected by flow cytometry; the RT-PCR was used to amplify and determine the TCR gene spectrotypes, and to analyze the clonality of abnormal cells. Sirolimus was first given to patients who did not gain efficacy from common agents. The results showed that lymphocytosis happened in all LGLL patients, but patients from West countries always displayed neutropenia while Chinese patients always displayed anemia. In 2 out of 4 patients from our hospital, the large granular lymphocytes (LGL) were difficult to be distinguished. In all 4 patients, almost all lymphocytes were CD3(+), CD8(+), and TCRα/β(+). TCR BV 24 gene family clones showed monoclonal TRBV 23, TRBV 20, TRBV 13.6, and TRBV 13.6, respectively. FCM results were consistent with those of RT-PCR. When 4 patients had been given sirolimus (6 mg first dose, 2 mg once a day) for about 1 week, hemoglobin level and reticulocyte count increased significantly without any serious side effects. It is concluded that the detection of specific lymphocyte monoclonal TCR BV 24 gene family by FCM contributes to the diagnosis of LGLL. Sirolimus is an effective agent without serious side effect for LGLL patients, especially for patients who cannot tolerate common drugs.

Enfermedades Autoinflamatorias / Autoinflammatory Diseases

Presentamos un artículo de revisión sobre las enfermedades autoinflamatorias, narrando su origen histórico y describiendo la estructura proteica y molecular del Inflamosoma, la clasificación actual de los trastornos autoinflamatorios y una descripción de las características inmunogenéticas y clínicas más sobresalientes de cada enfermedad.

We present a review article on the autoinflammatory diseases, narrating its historical origin and describing the protein and molecular structure of the Inflammasome, the current classification of the autoinflammatory diseases and a description of the immunogenetics and clinical characteristics more important of every disease.

Caracterização imunofenotípica de linfócitos B de memória na deficiência de IgA e imunodeficiência comum variável / Immunophenotypical characterization of memory B Iymphocytes in IgA deficiency and common variable immunodeficiency

Objetivo: A progressão da deficiência de IgA (DIgA) para imunodeficiência comum variável (ICV) tem sido relatada, embora não constitua regra geral. Postula-se que a associação com doenças autoimunes (DAIs) constitua fator de risco para tal progressão. Embora a fisiopatologia da ICV não esteja esclarecida, a redução de células B de memória class-switched (CD27+IgG-IgM-) tem sido relacionada a sua maior associação com autoimunidade. Por outro lado, na DIgA a persistência de células B imaturas IgM+ IgD+ foi associada à progressão para ICV. O objetivo foi comparar em pacientes com DIgA e ICV populações de células B de memória e correlacionar estas populações celulares à presença de DAIs em ambos grupos. Métodos: O estudo incluiu 56 pacientes adultos com DIgA ou ICV igualmente distribuídos em 4 grupos de acordo com a presença ou ausência de DAIs. As seguintes subpopulações de células B foram determinadas por citometria de fluxo de quatro cores: células B naive (CD19+IgM+), células B de memória c/ass-switched (CD27+IgM-IgD-) e células B de memória imaturas (CD27+IgM+ ou CD27+IgD+). Resultados: Os valores de células B naive e de células de memória c1ass-switched foram similares nos quatro grupos estudados. Os pacientes com DIgA ou ICV e DAIs associadas apresentaram valores igualmente aumentados de células B de memória imaturas CD27+IgM+ e CD27+IgD+ quando comparados a pacientes sem autoimunidade. Conclusões: Neste estudo foi demonstrado pela primeira vez persistência de células B de memória imaturas em pacientes adultos com DIgA e ICV associadas a doenças autoimunes. Especula-se se a persistência destas células possa constituir fator de risco para a progressão de DIgA para ICV.

Objective: Progression from IgA deficiency (IgAD) to common variable immunodeficiency (CVID) has been reported in some patients, but is not a general rule. It is postulated if association with autoimmune diseases (AIDs) could be risk factor for such progression. While the pathophysiology of CVID remains elusive, decreased numbers of classic (class-switched) memory B cells (CD27+IgG-IgM-) was correlated with increased rates of autoimmune features. By other hand, persistence of immature B cells (IgM+ IgD+) in IgA deficiency patients was correlated to progression from DIgA to CVID. The aim of this study was to compare memory B cell subpopulations in IgAD and CVID patients, and to assess the relationship between these populations and the presence of autoimmune diseases in both group of patients. Methods: This study included 56 adult patients with IgAD or CVID distributed in four groups according to the presence or absence of AIDs. The following B cell populations were determined by lymphocyte immunophenotyping by four-colour flow cytometry: narve B cells (CD19+IgM+), c1ass-switched memory B cells (CD27+IgM-IgD-) and immature B memory cells (CD27+IgM+ or CD27+IgD+). Results: Naive B cell and c1ass-switched memory B cells (CD27+IgG-IgM-) numbers were similar in all groups studied. IgAD and CVID patients with associated AIDs presented higher values of immature B cells (CD27 IgM+ and CD27+ IgD+) than patients without associated AIDs. Conclusions: This study reported for the first time the persistence of immature memory B cells in adult IgAD and CVID patients associated to autoimmune diseases. We speculate if persistence of immature B cells may constitute a rlsk factor for progression of IgAD to CVID.

Pathogenesis and clinical manifestations of juvenile rheumatoid arthritis / 소아과

Juvenile rheumatoid arthritis (JRA) is the most common rheumatic childhood disease; its onset is before 16 years of age and it persists for at least 6 weeks. JRA encompasses a heterogeneous group of diseases that is classified according to 3 major presentations: oligoarthritis, polyarthritis, and systemic onset diseases. These presentations may originate from the same or different causes that involve interaction with specific immunogenetic predispositions, and result in heterogeneous clinical manifestations. An arthritic joint exhibits cardinal signs of joint inflammation, such as swelling, pain, heat, and loss of function; any joint can be arthritic, but large joints are more frequently affected. Extra-articular manifestations include high fever, skin rash, serositis, and uveitis. The first 2 types of JRA are regarded as T helper 1 (Th1) cell-mediated inflammatory disorders, mainly based on the abundance of activated Th1 cells in the inflamed synovium and the pathogenetic role of proinflammatory cytokines that are mainly produced by Th1 cell-stimulated monocytes. In contrast, the pathogenesis of systemic onset disease differs from that of other types of JRA in several respects, including the lack of association with human leukocyte antigen type and the absence of autoantibodies or autoreactive T cells. Although the precise mechanism that leads to JRA remains unclear, proinflammatory cytokines are thought to be responsible for at least part of the clinical symptoms in all JRA types. The effectiveness of biologic therapy in blocking the action of these cytokines in JRA patients provides strong evidence that they play a fundamental role in JRA inflammation.

Aspectos inmunogenéticos del autismo: revisión / Immunogenetic aspects of autism: review

El autismo es un trastorno profundo o generalizado del desarrollo que afecta aproximadamente a cinco de cada diez mil niños a nivel mundial (5/10.000). En Maracaibo la incidencia es de 1,1/1000, con una relación por sexo masculino/femenino de 4:1. El trastorno autista es definido completamente con base en el deterioro de tres áreas: 1) Deterioro en la interacción social, 2) Deterioro en la comunicación y 3) Comportamiento estereotipado y repetitivo. El autismo es un trastorno con un gran componente genético y dentro de los modelos de herencia propuestos se encuentra la herencia oligogénica. Una de las estrategias utilizadas para la identificación de genes candidatos de susceptibilidad al autismo consiste en la utilización de endofenotipos, dentro de los cuales se encuentran la alteración cuantitativa y cualitativa de determinados componentes del sistema inmunitario, de igual forma se ha evidenciado una hipersensibilidad a grupos específicos de alimentos como la caseína y el gluten, todo lo cual ha llevado a la postulación de teorías inmunogenéticas en el autismo donde se implican principalmente los genes del complejo principal de histocompatibilidad. Aunque no se ha confirmado que los factores inmunogenéticos intervienen en la etiopatogénesis de los trastornos del comportamiento, como el autismo, diversos estudios han demostrado la influencia del complejo Antígeno Leucocitario Humano (siglas en inglés HLA) HLA DR4, DR13, DR11 y A2, entre otros genes, en el estatus clínico, riesgo y respuesta terapéutica de algunos desórdenes psiquiátricos. La escasa literatura existente demanda un mayor número de estudios relacionados con diferentes grupos étnicos y la participación del HLA; así como la importancia de este complejo en la patogénesis de enfermedades psiquiátricas

Autism is a generalized or pervasive developmental disorder that affects about five in ten thousand children worldwide (5/10.000). In Maracaibo the incidence is 1.1/1000, with a ratio of male/female, 4:1. The autistic disorder is defined entirely based on the impairment in three areas: 1) Impairment of social interaction, 2) Impairment in communication and 3) Stereotyped and repetitive behavior. Autism is a disorder with a large genetic component and a oligogenic inheritance model has been proposed. Quantitative and qualitative disturbances of certain components of the immune system in patients with autism have been used as endophenotype, one of the strategies used to identify candidate genes for susceptibility to autism. On the other hand the hypersensitivity to specific groups of foods such as casein and gluten has become clear, which has led to the postulation of immunogenetics theories in autism, which mainly involve genes of the histocompatibility major complex. Although it has not been confirmed that immunogenetics factors could be involved in the etiopathogenesis of autism, several studies have shown the influence of the complex Human Leucocyte Antigen (HLA) HLA DR4, DR13, DR11, A2 and others genes in the clinical status, risk and therapeutic response of some psychiatric disorders. The lack of literature demands a greater number of studies related to different ethnic groups and the participation of HLA, as well as the importance of this complex in the pathogenesis of psychiatric illness

Caracterización inmunogenética de pacientes con espondilitis anquilosante en Argentina / Immunogenetic profile of ankylosing spondylitis in Argentina

Objetivo: Evaluar la influencia del polimorfismo genético del HLA clase I y II, TNF e IL1 en pacientes argentinos con espondilitis anquilosante (EA). Material y métodos: Este fue un estudio de asociación en el que se incluyeron pacientes con EA clasificados de acuerdo a los criterios de New York modificados. Se registraron datos demográficos y clínicos de la enfermedad. Un grupo no relacionado, pero pareado, de 154 personas fue utilizado como grupo control. La genotipificaciónfue realizada utilizando técnicas basadas en la reacción en cadena de la polimerasa. Se evaluaron alelos HLA clase I (A y B) y II (DR), polimorfismos de nucleótido simples del TNF (-238 y 308) y del gen IL1 (-511 y +3954). Resultados: Se incluyeron 52 pacientes con EA, de los cuales 90,4% fueron varones, con una edad mediana de 44 años rango intercuartilo (RIQ) 34-53. Confirmamos la asociación del HLA-B27 con la enfermedad (90,4% vs. 5,2%, con OR: 171,5, p = 1x10-30). El subtipo más frecuente tanto en pacientes como en controles fue el B27*05 (85%). La comparación de alelos de clase A y B no B27 entre controles y pacientes no mostró diferencias significativas. La comparación entre los alelos clase II evidenció una mayor frecuencia del HLA-DR1 (59,6% vs. 20%, OR: 6,1, p = 1x10-5). El genotipo TNF -308 GA fue un factor de riesgo (94% vs. 81%, OR: 3,96, p = 0,02), mientras que el genotipo -238 GA fue protector (53% vs. 76%, OR: 0,19, p >0,0001). El alelo IL1β-511C se asoció con la EA (66% vs. 53%, OR: 1,74, p = 0,03). Conclusión: En el presente estudio, hemos replicado por primera vez en la población argentina la influencia del HLA, TNF e IL1 ;en la EA. Estos hallazgos permiten una comprensión homogénea de la fisiopatogenia de la enfermedad.

Objective: To determine the influence of the genetic polymorphismof HLA class I and II, TNFα and IL1β in Argentinean patients withankylosing spondylitis. Material and Methods: This was an association study where AS patients according to modified New York criteria were included. Werecorded demographic and clinical data of the disease. A non related but age and sex matched group of 154 people was used as controls. Genotyping was performed using polymerase chain reaction (PCR) techniques. We evaluated HLA class I (A and B) and class II (DR), single nucleotide polymorphism of the TNFα (-238 and 308) and IL1β (-511 and +3954). Results: We included 52 patients with AS of whom 90.4% were male with a median age of 44 years (IQR 34-53). We confirm the association of HLA-B27 with disease (90.4% vs 5.2%. OR 171.5, p= 1x10-30). The most common subtype in both patients and controls was B27*05 (85%). Comparison between class A and B alleles non B27 between controls and patients did not show significant differences. Comparison between class II alleles showed a statistically significant higher frequency of HLA-DR1 in AS patients (59.6% vs.20% OR 6.1, p = 1x10-5). TNF -308 GA genotype was a risk factor for AS (94% vs. 81% OR 3.96 p = 0.02), while the -238 GA genotype had a protective effect and was more frequently observed in controls (76% vs. 53%, OR 0.19, p >0.0001). IL1β -511 allele wasassociated with a higher susceptibility to AS (66% vs. 53%, OR 1.74 p = 0.03).Conclusion: In the present study, we have replicated for the first time in the Argentinean population, the influence of HLA, TNFα, and IL1β in patients with AS. These findings allow a uniform understanding of the physiopathology of the disease.

Mycobacteria and innate cells: critical encounter for immunogenicity.

Protective immunity against mycobacterial infections such as Mycobacterium tuberculosis is mediated by interactions between specific T cells and activated macrophages.To date,many aspects of mycobacterial immunity have shown that innate cells are the key elements that substantially influence the subsequent adaptive host response.During the early phases of infection,phagocytic cells and innate lymphocyte subsets play a pivotal role.Here we summarize the findings of recent investigations on macrophages,dendritic cells and gammadelta T lymphocytes in the response to mycobacteria.