A person is exposed to many pathogens throughout their lifetime, and with the resolution of each infection, there remains a pool of pathogen-specific immune cells that protect that person from re-infection with the same pathogen. However, there is a great deal of evidence to suggest that the pool of pathogen-specific memory cells can also participate in the immune response to future infections with unrelated pathogens. Many believe T cells to be cross-reactive in nature because of their interaction with self antigens during development in the thymus and their interaction with foreign antigens once in the periphery. There are many features of the interaction between a T cell and its ligand that facilitate this cross-reactive nature. Based on solved crystal structures, relatively few contacts are required for a stable interaction, and that interaction is often mediated by the flexible CDR3 loops of the T cell receptor that accommodate ligands of various structure. There is also evidence in the murine and human systems that subsets of virus-specific memory CD8 T cells take on an activated phenotype upon infection with an unrelated virus. In murine models, these memory T cell subsets could kill target cells, secrete several cytokines, and proliferate in response to a cross-reactive stimulation, suggesting that a cross-reactive T cell response could impact the outcome of a viral infection. In fact, upon heterologous infection, mice immune to a previous virus were often protected, having lower titers of the second unrelated virus, their epitope-specific and T cell receptor repertoires were often skewed, and they were more prone to immune-mediated pathologies. All of these observations coincided with the presence of cross-reactive T cell responses. Thus, we define heterologous immunity as changes in viral replication and the disease pathology associated with that viral infection as a result of the host's history of infection, and this can be mediated, in part, by cross-reactive CD8 T cell responses. Since many human viral infections are associated with a wide range of disease states, we questioned whether cross-reactive CD8 T cell responses occurred as commonly as they appeared to occur in the murine models and whether they influenced the outcome of such infections. Epstein-Barr virus (EBV) infects over 90% of the U. S. population and has a large genome with the capacity to encode a multitude of T cell epitopes. The first part of this thesis research focuses on the identification of cross-reactive CD8 T cell responses with specificity for known epitopes derived from EBV, a common human virus. We directed our study to HLA-A2-restricted responses because of the common expression of this MHC Class I allele in the U. S. population. This study resulted in the detection of cross-reactive responses with five different specificities that involved either the immunodominant lytic EBV-BMLF1280 epitope or the latent EBNA 3A596epitope. Three of the cross-reactive responses had specificity for epitopes derived from another unrelated, but common, human virus, influenza A virus (IV). Each of these cross- reactive responses had the potential to participate in the collective immune response to acute EBV infection. EBV is also well-suited as a model system to study heterologous immunity in humans, as infection at an early age is frequently asymptomatic, while the same infection during adolescence often results in an immune-mediated syndrome, infectious mononucleosis (IM). Since older individuals have presumably been exposed to more pathogens in their lifetime and, therefore, would have memory CD8 T cell pools with more extensive specificities, we hypothesized that acute EBV infection activated cross-reactive memory CD8 T cell responses that promoted the development of IM. In order to determine if the cross-reactive responses we identified above contributed to the immune response to acute EBV infection, we first screened the blood of IM patients for cross-reactive T cells with specificity for EBV-BMLFl280 and IV-M158. The total number of M1-specific T cells of 5 of 8 patients was increased at presentation with IM, which was suggestive of their specific activation during the EBV infection since a bystander mechanism would have resulted in 8 out of 8 patients having increased numbers of M1-specific T cells. Our hypothesis was further supported by the fact that we clearly detected cross-reactive T cells capable of recognizing both BMLF1 and M1 epitopes in the blood of 2 of the 5 IM patients with an augmented M1-specific T cell frequency. Furthermore, the M1-specific TCR repertoires of those two patients were dramatically skewed, which was an indication of cross-reactive M1-specific T cell expansions and, therefore, participation in the lymphoproliferation characteristic of IM. In addition, T cell lines derived from 3 out of 8 healthy donors with previous exposure to both viruses contained a subset of T cells that responded to both BMLF1 and M1 epitopes, suggesting that these cross-reactive cells are often maintained in memory. These cross-reactive T cells were cytotoxic and produced MIP-1β, IFNγ, and TNFα, functions which could potentially promote the symptoms of IM and, indeed, may have been contributed to the severe case of IM noted in one patient. The final part of this thesis research focused on defining the structure of the cross-reactive TCR that recognized both BMLF1 and M1 epitopes, which have only 33% sequence similarity. In addition, we examined the cross-reactive TCR repertoire organization of multiple individuals to determine the breath and, therefore, the likelihood that this cross-reactive T cell response will occur. These studies revealed that a wide range of Vα and Vβ families can mediate interaction with both epitopes and that the cross-reactive TCR repertoire was unique to each individual, relying heavily on the T cell clones present in that individual's private BMLF1- and M1-specific repertoires. We also observed an increased frequency of TCRs with longer CDR3 regions within the cross-reactive repertoire, which were often extended by non-bulky amino acid residues that could provide these TCRs with more flexibility in order. to accommodate the two different epitope structures. Given that we detected a cross-reactive T cell response with specificity for two immunodominant epitopes derived from two of the most common human viruses among people that share one of the most common MHC Class I alleles in the U. S. population, we predict that cross-reactive T cells are common components of human immune responses. The variability in the magnitude and specificity of each cross-reactive T cell response is dependent on each individual's unique history of infection and th,eir unique TCR repertoire, and such responses likely represent one of many factors that could explain the individual variability in disease severity associated with EBV and many other human viral infections.

El documento digital no refiere un asesor / Publicación a texto completo no autorizada por el autor / Evalúa si la asociación entre el PTCL-NOS y la infección por el EBV es un factor pronóstico independiente en la sobrevida global (OS) en pacientes con PTCL-NOS atendidos en el Instituto Nacional de Enfermedades Neoplásicas (INEN). Se revisan 100 historias clínicas del INEN con diagnóstico de PTCL-NOS y se reevalúa el diagnóstico histopatológico e inmunofenotípico determinado con inmunohistoquímica. Se seleccionan 65 casos. Se realiza la determinación de EBV en las muestras parafinadas con la técnica de hibridación in situ (ISH-EBER). Existe 45% de los casos positivos para ISH-EBER. El promedio de edad es de 50 años y 29% son mujeres. La proporción de pacientes con síntomas B y sin síntomas B es similar. Los estadios son usualmente avanzados, con lactato deshidrogenasa (DHL) elevada. El índice pronóstico internacional (IPI) es intermedio-alto o alto en la mayor parte de los casos. La respuesta al tratamiento es generalmente pobre. Histológicamente, todos los casos tienen un patrón difuso y polimorfo de células T maduras, con atipia variable. 67% de casos tienen fenotipo CD4 y 23% fenotipo citotóxico. / Tesis

To view the Shelves Catalogue in the correct format: 1. Click "view"; 2. Click "page display"; 3. Click "Two Page View"; 4. Click "Show Cover Page in Two Page View" / This study explores how a narrative view of collecting can be expanded and applied to Ilya and Emilia Kabakov’s installations, as well as to my own artworks. It focuses on personal and intimate collections of everyday objects that serve to edify their owner’s sense of being. The project is undertaken in order to arrive at new interpretations of the themes of loss, meaning and absence through Mieke Bal’s (2006) narrative theory, Susan Pearce (1994) and Mikhail Epstein’s (1995) methods of collecting and Jean Baudrillard’s (1996) notions of the collector. These theories are applied to selected installations from the Kabakovs’ series Ten Characters. My own exhibition, S(h)elves, is an exploration of collections, underpinned by conceptually relevant theories. Conclusions are reached by means of literary analysis and comparison of selected theorists and artworks. A reflexive approach to art-making means that theories inform art-making processes while practical developments facilitate re-evaluated perceptions which lead to new insights. / Art History, Visual Arts and Musicology

The practical part of thesis follows up the art processing of Mark Epsteins' screenplay Vlci a psi. The script is set in times after WW2, describing historical situation of the evacuation of Sudetenland Germans from previous Czechoslovakia in 1945. The practical part itself shows visual concept and structure which is presented by drafts of decorations and scenes. The decorations are visualized by coloured perspective views, drafts of each building and schematic designs. The teoretical part of the thesis is about analysis and parametres of stated films works that are very closely related to this issue and shows historical situation in film language. The visual part and its structure are shown in individual analysis. Results of the teoretical part were one of the basis for definition and visualisation of the practical part of thesis. Last but not the least the study of historical links, documents and internet portals containing given topic were another important teoretical source. These results of my thesis can be used as a source of interesting informations for a public, as an inpiration for film productions or as a study material for film students.

Epstein-Barr virus (EBV) BKRF4 gene product is a tegument protein encoded by a gene with no sequence homology outside of the gamma subfamily of Herpesviridae. Its positional homologs are necessary for an efficient viral lytic program, in particular viral progeny egress and primary infection. To characterize BKRF4 in this regard, EBV recombinant viruses deficient for BKRF4 were developed using site-directed mutagenesis and a bacterial artificial chromosome (BAC)-based recombineering system. Stable human embryonic kidney (HEK) 293 cell lines containing these genomes were generated and the phenotypes of these mutants were analyzed following stimulation of the viral lytic cycle. During the lytic program, BKRF4-null cell lines showed decreased protein expression of various EBV lytic genes that were analyzed using immunostaining and flow cytometry. Reduced amounts of extracellular viral progeny were observed when quantified by real-time PCR and infectivity assays as compared to wild type. These findings suggest an active role of BKRF4 in EBV infection, possibly in viral egress.

Le virus Epstein-Barr (EBV) est un gamma herpèsvirus humain infectant plus de 95 % de la population mondiale. Lorsque la primo-infection a lieu pendant l'adolescence ou à l'âge adulte, elle peut induire la mononucléose infectieuse (MNI), cette maladie est le plus souvent bénigne. EBV est aussi associé à un certain nombre de cancers de type lymphome (lymphomes de Burkitt et d'Hodgkin) et de type carcinome (carcinomes gastriques et indifférenciés du rhinopharynx). L'importance des protéines de latence du virus dans l'apparition des tumeurs a été très étudiée. Des études récentes montrent que les protéines lytiques d'EBV sont aussi très importantes pour l'apparition et le développement des tumeurs. Le complexe Hélicase-Primase (H-P) du virus herpès simplex 1 (HSV-1, alpha herpèsvirus) est la cible de nouveaux antiviraux. Les activités ATPase, hélicase et primase du complexe d'HSV-1 ont été largement étudiées, mais aucune information structurale du complexe H-P n'est disponible actuellement pour un membre des herpèsvirus humains. Nous avons entrepris l'étude du complexe H-P d'EBV (BBLF4 : hélicase, BSLF1 : primase et BBLF2/3 : sous-unité accessoire) afin de caractériser sa structure et les activités qu'il porte. Nous avons pu établir les conditions d'expression et de purification du complexe et débuter des études structurales et enzymatiques préliminaires. Nous avons pu observer une activité ATPase basale du complexe indépendante de la présence d'un substrat ADN simple brin. Nous observons deux formes solubles du complexe lors des purifications, une présentant probablement une stœchiométrie proche de 1/1/1 et une seconde forme ayant surement un excès de la protéine Hélicase (BBLF4). Ces premiers résultats apportent des informations nouvelles pour le complexe H-P d'EBV et doivent être poursuivis afin de les confirmer et de pouvoir les comparer avec ceux déjà connus pour le complexe H-P d'HSV-1. / Epstein-Barr Virus (EBV) is a human herpesvirus largely present worldwide. When primary infection occurs during adolescence or adulthood, it could cause infectious mononucleosis (IM). This disease is most of the time minor. EBV is also associated with several cancers like lymphomas (Burkitt's lymphoma and Hodgkin's lymphoma) or carcinomas (gastric carcinoma and nasopharyngeal carcinoma). Latent proteins of the virus are largely studied and are important for apparition of tumors. Recent studies show that lytic proteins are also important for tumor apparition and progression. The Helicase-Primase complex (H-P) of herpes simplex 1 (HSV-1), a well-known herpèsvirus, is a target for new antiviral drugs. ATPase, helicase and primase activities of HSV-1 complex are well studied, but no information is available for the structure of the H-P complex of human herpesvirus. We studied the H-P complex of EBV (BBLF4: helicase, BSLF1: primase and BBLF2/3: accessory subunit) to characterize its structure and enzymatic activities. We describe the expression and purification conditions and begin preliminary studies on structure and activities of the H-P complex. We show a basal ATPase activity that is DNA single strand independent. We were able to purify two forms of the H-P complex, the first has a stoichiometry close to 1/1/1 and the second one has an excess of helicase protein (BBLF4). These preliminary results on H-P complex of EBV have to be validated with other experiments before being compared to information already known for the HSV-1 complex. Key words : EBV, Helicase-Primase complex, BBLF4, BSLF1, BBLF2/3, ATPase, stoichiometry.

Submitted by Susimery Vila Nova (susimery.silva@ufpe.br) on 2015-04-10T19:19:57Z No. of bitstreams: 2 tese final para impressão 1.pdf Joacilda.pdf: 3160703 bytes, checksum: 77f3910f7f992488c2ed2eada2b36dcf (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-04-10T19:19:57Z (GMT). No. of bitstreams: 2 tese final para impressão 1.pdf Joacilda.pdf: 3160703 bytes, checksum: 77f3910f7f992488c2ed2eada2b36dcf (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2012-05-30 / Leucemia linfoide aguda (LLA) é o câncer pediátrico mais comum e etiologicamente não apresenta um modelo definido, uma vez que apresenta uma história natural biologicamente diversificada. Fatores têm sido relacionados ao sistema imunológico como risco/proteção ao desenvolvimento de LLA, considerando-se como plausíveis o papel do sistema imune frente às infecções na infância, e a inter-relação dessas infecções com mecanismos envolvendo as Hipóteses da Higiene e da Adrenal. A proposta desse estudo foi investigar uma possível associação entre alergia prévia, bem como a ativação do eixo adrenal, pautado na Hipótese da Adrenal, com o desenvolvimento de leucemia linfoide aguda na infância e adolescência. Trata-se de um estudo do tipo caso-controle não pareado de base hospitalar, cuja amostra foi constituída de 60 crianças e adolescentes com diagnóstico incidente de leucemia linfoide aguda não T, classificadas pela avaliação da medula óssea através do mielograma e imunofenotipagem e 120 controles selecionados com proporcionalidade com relação à idade e sexo a partir dos casos e oriunda dos estados de Pernambuco e Paraíba no nordeste brasileiro, entre 2008 e 2011. A coleta dos dados consistiu na aplicação de questionário estruturado para identificação de alergias como asma, rinite alérgica, antecedente de urticária e dermatite atópica, uso prévio de glicocorticoides, além de exame clínico e coleta de sangue para dosagem de IgE total, cortisol basal, ACTH, marcador de infecção prévia pelo EBV e parvovírus B19 através da dosagem de IgG. Outras variáveis como aleitamento materno, peso ao nascer, escolaridade materna, infecção materna na gestação e número de pessoas no domicílio também foram analisadas. Para a análise estatística foram utilizados Teste de associação de 2, Teste Exato de Fisher, Odds Ratio, Regressão Logística Binária e Regressão Logística Múltipla. Os resultados encontrados na análise univariada (p < 0,20) foram: Asma ( pvalor = 0,116), Rinite Alérgica (p-valor=0,032), Antecedente de Urticária (p-valor = 0,011), Dermatite Atópica (p-valor = 0,086), Nível Sérico Elevado de IgE Total (p-valor = 0,00), Nível Elevado de Cortisol Basal (p-valor = 0,004), Infecção Prévia pelo EBV (p-valor = 0,143), Infecção Prévia por Parvovírus B19 (p-valor = 0,068). Após o modelo ajustado através da análise de regressão logística múltipla persiste a significância de uma relação inversa entre Asma com p-valor = 0,044 e OR/IC 95% 0,14 (0,02 – 0,95), Nível Sérico Elevado de IgE Total com p-valor = 0,001 e OR/IC 95% 0,10 (0,02 – 0,41), além de Níveis Elevados de Cortisol apresentando p-valor 0,004 e OR/IC 95% 0,16 (0,04 – 0,56); Para infecção Prévia pelo Parvovírus B 19 o resultado expressa risco p-valor = 0,037 e OR/IC 95% 2,19 (1,05 – 4,57). Asma e Níveis Séricos Elevados de IgE Total e ainda Níveis Elevados de Cortisol Basal, parecem estar relacionados com modificações na resposta imune e como consequência promoveriam uma diminuição de clones leucêmicos, desempenhando um papel de proteção a crianças e adolescentes contra LLA. A infecção prévia pelo parvovírus B 19 está associada com aumento de risco de LLA.

Orientador: Sandra Cecilia Botelho Costa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T03:22:40Z (GMT). No. of bitstreams: 1 Pasquotto_Juliana_M.pdf: 2465167 bytes, checksum: dcd2cc122494bab62d8ab495927b1f0e (MD5) Previous issue date: 2008 / Resumo: O Vírus Epstein-Barr (EBV) e o Citomegalovírus (HCMV) são membros da família Herpesvírus. São encontrados em aproximadamente 90% dos indivíduos em idade adulta. A infecção ocorre, geralmente, na infância e é assintomática na maioria dos casos, persistindo de forma latente durante toda a vida do indivíduo. A transmissão destes vírus ocorre principalmente pela saliva, sangue e órgãos transplantados. O EBV está relacionado com a mononucleose infecciosa, doença linfoproliferativa (PTLD), leucemia de células pilosas em pacientes com imunodeficiência congênita ou adquirida e doença de Hodgkin. O risco de um paciente transplantado desenvolver linfoma é 28 a 50 vezes maior do que os indivíduos da população geral. Um dos fatores de risco para o desenvolvimento da PTLD são a variedade e intensidade da imunossupressão utilizada no paciente pós-transplante, idade do receptor e sorologia viral (EBV, CMV). Dependendo da idade do receptor, do tipo de transplante e dos fatores de risco, a prevalência da PTLD pode variar de 0.5% a 22%. Em transplantados pediátricos renais a prevalência chega a atingir 37%. A principal medida terapêutica para o controle da PTLD é a diminuição ou mesmo a retirada total da imunossupressão. Portanto a rejeição do enxerto se torna um problema bastante comum, que compromete a qualidade e/ou expectativa de vida dos pacientes. A introdução de testes laboratoriais rápidos e precoces permite aos clínicos detectar a replicação viral do EBV e diagnosticar, consequentemente, a infecção ativa antes do início da doença. Isso proporciona a oportunidade de iniciar o tratamento específico precocemente. Foram estudadas amostras de sangue e soro de 46 pacientes submetidos a transplantes de células hematopoéticas, acompanhados no Serviço de Transplante de Medula Óssea (STMO) do Hospital das Clínicas da UNICAMP/HEMOCENTRO. Trabalhamos no estudo para diagnosticar a infecção ativa e quantificar a carga viral do vírus Epstein-Barr (EBV) em pacientes transplantados de células hematopoéticas. Relacionar infecção ativa do vírus Epstein-Barr com o Citomegalovírus (CMV) e verificar a incidência da Doença linfoproliferativa e a Doença do enxerto contra o hospedeiro (GVHD) nos pacientes estudados. Diagnosticamos infecção ativa pelo EBV em 22 (47,8%) pacientes que apresentaram uma carga viral muito baixa (média de 29 cópias/ul). Co-infecção entre EBV e CMV ocorreu em 15/46 pacientes (32,6%). Doença por CMV ocorreu em 7/46 (15,2%) pacientes no trato gastrintestinal. Todos estes doentes apresentaram infecção ativa pelo CMV e 4/7 (57%) apresentaram infecção ativa pelo EBV. Um destes pacientes foi a óbito por doença por CMV. Verificamos que nenhum dos pacientes apresentou doença linfoproliferativa relacionada ao EBV. Os casos de co-infecção ativa EBV+CMV em relação à ocorrência de GVHD foram estatisticamente significantes (p=0.001). Concluímos que a infecção pelo CMV ainda é a maior causa de morbidade e mortalidade nos pacientes após o transplante. A qPCR é uma ferramenta útil para verificar os pacientes que reativaram pelo EBV após o transplante e pode auxiliar na prevenção da doença linfoproliferativa causada pelo EBV juntamente com a identificação dos fatores de risco associados. Verificamos a ocorrência e significância do GVHD e infecção ativa pelo CMV, mas não observamos esses mesmos resultados comparados ao EBV / Abstract: Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV) are members of herpesvirus family. They are found in approximately 90% of the individuals in adult age. The infection generally occurs subclinicaly during the childhood in the major of the cases persisting in latent form during all the life of the individual. The transmission of these viruses occurs mainly for the saliva, blood and transplanted organs. EBV is related with mononucleose infectious, lynfoproliferative disease (PTLD), leukemia of hair cells in patients with congenital or acquired immunodeficiency and Hodgkin¿s disease. The risk of a transplanted patient to develop linfoma is 28 to 50 % more than other individuals of the general population. One of the risk factor for the development of the PTLD is the variety and intensity of the imunossupression used in the patient after-transplant, age of the recipient and viral serology (EBV, CMV). Depending on the age of the recipient, the type of transplant and the risk factor, the prevalence of the PTLD can vary of 0.5% 22%. In renal pediatric transplantation, the prevalence can arrives to reach 37%. The main therapeutical measure for the control of the PTLD is the reduction or total withdrawal of the imunossupression. Therefore the lost of graft is a common problem, that compromises the quality and/or life expectancy of the patients. The introduction of early and rapid laboratorial tests can permit to the physicians to detect the viral response and detect the active EBV infection before the disease. This provides the chance to initiate the specific treatment. We studied samples of blood and serum of 46 patients submitted to hematopoietic stem cell transplantation at the Bone Marrow Transplant unit of the University Hospital of the UNICAMP/HEMOCENTRO. We worked in the study to diagnosis the active infection and quantify the viral load of the Epstein-Barr virus (EBV) in transplanted patients of hematopoetic stem cells, to relate active EBV infection with active CMV infection and to verify the incidence of the lynfoproliferative disease and graft versus host disease (GVHD) in the studied patients. Active EBV infection detected by Real-Time PCR occurred in 22 patients (47,8%). The viral load found was very low (range 29 copies/ul). Co-infection between EBV and CMV occurred in 15/46 patients (32,6%). CMV disease occurred in 7/46 (15,2%) patients in the gastrointestinal tract. All these patients had active CMV infection and 4/7 patients (57%) had active EBV infection. One of these patients died by CMV disease. No patient presented lymphoproliferative disease related to the EBV. The cases of active EBV and CMV (co-infection) infection in relation to the occurrence of GVHD had been statisticaly significant (p=0.001). We conclude that the active CMV infection is already the most cause of morbidity and mortality of the patients after the transplant. The qPCR is a useful tool to verify the patients who had active EBV infection after the transplant and the identification of the risk factors associates prevention the development of the lymfoproliferative disease caused by the EBV. We verify the occurrence and significance of the GVHD and active CMV infection, but we do not observe these same results related to the EBV / Mestrado / Mestre em Farmacologia

Made available in DSpace on 2014-06-12T18:30:24Z (GMT). No. of bitstreams: 2 arquivo8067_1.pdf: 2863981 bytes, checksum: c052a8dab422808863f0e213e2a49701 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2004 / INTRODUÇÃO: O vírus Epstein-Barr, um herpesvírus que infecta mais de 90% da população mundial, pode desencadear ou agravar alterações auto-imunes, assim como pode anteceder o aparecimento das manifestações clínicas e imunológicas do Lúpus Eritematoso Sistêmico (LES). Como os auto-anticorpos parecem exercer papel central na patogênese do LES, é importante correlacionar a presença e o título de anticorpos anti-EBV com a atividade do LES. OBJETIVO: Verificar a associação entre atividade do Lúpus Eritematoso Sistêmico, por meio dos critérios do SLEDAI, e a avidez das imunoglobulinas IgG anti-EBV. PACIENTES E MÉTODOS: Foi realizado estudo tipo caso-controle, envolvendo 66 pacientes, atendidos no ambulatório de Reumatologia do Hospital das Clínicas da Universidade Federal de Pernambuco (HC-UFPE), no período janeiro de 2002 a fevereiro de 2003, distribuídos em dois grupos: caso, composto por 22 pacientes com LES em atividade e SLEDAI > 4, e controle, integrado por 44 pacientes com doença inativa, diagnosticada por SLEDAI ? 4. A presença e o índice de avidez de anticorpos IgG anti-EBV foram determinados pela técnica de ELISA. (Enzygnost? anti-ebv Dade Behring), no Setor de Virologia do Laboratório de Imunologia Keizo Asami (LIKA). Os índices de avidez e respectivas classificações da infecção foram: < 20, infecção reativada; entre 20 e 40, infecção indeterminada, > 40, infecção passada. RESULTADOS: Identificou-se positividade no teste de detecção de IgG para EBV em 21 (95,5%) casos e em 40 (90,9%) controles. O índice de avidez alcançou valores ?40 em 54 (88,5%) pacientes, sendo 34 (85%) do grupo controle e 20 (95,2%) do grupo caso; esteve entre 20 e 40 exclusivamente em 5 (12,5%) pacientes do grupo controle, e foi inferior a 20 em 2 (3,3%) pacientes. Adotando-se 20, 30 ou 40 como ponto de corte do índice de avidez, para diagnóstico de reativação da infecção por EBV, detectou-se terem sido classificados como infecção reativada, respectivamente, 1 (4,8%) paciente do grupo caso e 1 (2,5%) do grupo controle; 1 (4,8%) do grupo caso e 4 (10%) do grupo controle, 1 (4,8%) no grupo caso e 5 (12,5%) no grupo controle. CONCLUSÃO: A modificação do ponto de corte não alterou a distribuição dos pacientes com infecção ativa do grupo caso, mas o fez no grupo controle. Não ter sido possível demonstrar, no presente trabalho, associação entre a atividade do EBV e a do LES corroborou relatos semelhantes na literatura consultada. Esse fato parece indicar que a não eliminação dos linfócitos B infectados se deve a falha no mecanismo de apoptose ou na ação de linfócitos T citotóxicos permitindo a progressão do LES

Les lymphoproliférations survenant après transplantation sont une situation rare mais préoccupante car mettant en jeu la survie des patients. Ces hémopathies ont des caractéristiques épidémiologiques et physio-pathologiques qui les distinguent des lymphomes du sujet immunocompétent. Nous nous sommes intéressé à l’analyse des facteurs de risque associés aux lymphomes post-greffe et à la recherche de facteurs pronostiques de survie des patients par l’analyse détaillée des registres américain et français de patients transplantés rénaux. Le Registre Français des lymphomes survenant après transplantation rénale a permis de recenser tous les cas de syndromes lymphoprolifératifs se développant chez des patients adultes survenant entre le 1er janvier 1998 et le 31 décembre 2007. Tous les centres français de Transplantation rénale ont participé. Nous avons recensé 500 cas de lymphomes sur une période de 10 ans. Les différentes analyses de cette base de données ont donné lieu à la publication d’une analyse intermédiaire sur les 230 premiers cas, à une publication consacrée à l’incidence et aux facteurs de risque de développement des lymphomes surla cohorte complète et à une publication concernant les facteurs pronostiques de décès des patients porteurs d’une lymphoprolifération avec établissement d’un score de risque spécifique de cette population. D’autre part, cette base de données unique au monde représente un support intéressant pour le développement de travaux de recherche: étude de l’origine des cellules tumorales, étude des facteurs de susceptibilité pharmacogénétique au développement des lymphoprolifération post-greffe, étude des microRNA de l’EBV dans les lymphomes post-greffe. / Post transplant lymphoproliferative disorders (PTLD) are a rare but serious complication occurring after kidney transplantation. Features of PTLD are specific and different of those of immunocompetent patients. We studied incidence, risk factors for development of PTLD and prognostic factors of patients with PTLD using two databases: American and French. The French Registry of PTLD enrolled all adult patients with PTLD occurring between the 1st January 1998 and the 31st December 2007 from all transplant centers in France. Five hundred patients were included in the Registry. This enables us to analyse first the incidence and risk factors of PTLD and second the risk factors of kidney recipients’ survival. We constructed a new prognostic score specific of transplant patients. Finally, the French Registry gave us the opportunity to support others research projects: determination of the origin of tumoral cells, analysis of pharmacogenetic factors associated with the risk of developing PTLD, study of EBV microRNA in lymphoproliferations.