Introdução: A Artrite Idiopática Juvenil (AIJ) inicia-se principalmente no intervalo etário de oito a catorze anos, podendo estar associada a déficit de crescimento e atraso puberal. O estadiamento de Tanner e a avaliação ultrassonográfica da pelve podem detectar atrasos no desenvolvimento puberal. Objetivos: Comparar a maturação sexual das meninas com AIJ a controles saudáveis, por meio da avaliação clínica dos estágios de Tanner e dos parâmetros da ultrassonografia (US) pélvica e relacionar esses achados aos níveis de hormônios sexuais e fatores relacionados à doença. Comparar, também, os dados antropométricos e a idade da menarca entre os dois grupos e relacioná-los a fatores de risco ligados à AIJ. Delineamento: Estudo transversal com grupo controle Metodologia: O estudo foi realizado com 44 meninas com AIJ e 59 controles com idades entre seis e dezoito anos incompletos, sem uso de glicocorticoides há no mínimo seis meses e sem outras doenças crônicas concomitantes. O diagnóstico de AIJ foi realizado de acordo com critérios da Liga Internacional das Associações de Reumatologia (ILAR). Foi realizada avaliação antropométrica, e a maturação sexual foi avaliada por meio dos estádios de Tanner. A US pélvica abdominal foi utilizada para avaliar as medidas do útero dos ovários e o índice de pulsatilidade das artérias uterinas (IP). Foram medidos níveis hormonais de FSH, LH, estrógeno, progesterona e IGF-1 nas meninas com AIJ. Resultados: Os parâmetros da US pélvica foram correlacionados aos estágios de Tanner no grupo controle (p <0,001). Todas as medidas de útero e ovários foram menores nas meninas com AIJ quando comparadas ao grupo controle. A média do IP das artérias uterinas foi maior nas meninas com AIJ. Estratificando-se por idade, o volume do útero foi menor nas meninas com AIJ na faixa etária de 10-11 anos (p < 0,004) e 14-15 anos (p=0,042), e a relação corpo/cérvice AP foi menor no intervalo de 10-11 anos (p=0,007). Os níveis de LH e estradiol foram fortemente relacionados ao aumento dos órgãos pélvicos (p<0,001) e inversamente com IP médio das artérias uterinas (p<0.01). O escore z do IMC e da estatura foi menor nas meninas com AIJ em relação ao grupo controle (p=0,032 e p=0,041 respectivamente). As meninas com AIJ poliarticular e com maior dose cumulativa de glicocorticoide apresentaram a maior chance de ter baixa estatura. Não houve diferença entre os grupos AIJ e controles com relação à idade da menarca. A altura final e a diferença entre essa altura e a altura-alvo familiar não foi diferente entre as meninas com AIJ e as do grupo controle. Conclusão: Nosso estudo mostrou que, mesmo sem uso de glicocorticoide há mais de seis meses, as crianças com formas mais graves de AIJ e que necessitaram de doses maiores de glicocorticoide estão mais suscetíveis ao retardo no crescimento e atraso no início da puberdade. A US pélvica demonstrou ser um exame sensível para avaliação da maturação sexual de meninas, identificando atrasos nas meninas com AIJ não percebidas por meio da avaliação clínica pelos estágios de Tanner. / Introduction: Juvenile Idiopathic Arthritis (JIA) manifests at the 8 to 14-year age span and is often associated with growth deficit and puberty delay. Tanner staging and pelvic ultrasonography (US) can be used to detect pubertal delays. Objectives: To compare sexual maturation in JIA girls and healthy controls (HC) by clinical evaluation with Tanner stages and pelvic US parameters and to correlate these findings with sexual hormone levels and disease related factors. Additionally, to compare anthropometric data and menarche age between groups and to correlate such findings with disease related risk factors in JIA patients. Study design: Cross-sectional study. Methods: 44 JIA and 59 healthy girls, aged six to 18 years, free of steroid use in the last six months and with no concomitant chronic diseases were included the study. JIA was diagnosed after the International League of the Rheumatology Associations (ILAR) criteria. Anthropometric and sexual development evaluations by Tanner staging were performed Pelvic US was performed to measure uterus, endometrial thickness, ovaries and uterine artery pulsatility index. Sexual hormone levels were measured in JIA girls. Results: Pelvic US parameters correlated with Tanner stages in HC (p <0.001). All uterine and ovarian measurements were smaller in JIA girls than in HC. Mean uterine artery PI was greater in JIA girls. Uterine volume was smaller in JIA girls at the 10 to 11 (P=0.004) and 14 to 15 year (p=0.042) age strata and the anteroposterior body cervix ratio was smaller in JIA girls the 10 to 11 year stratum (p=0.007). LH and estradiol levels were strongly correlated with pelvic organ size. (P<0.001) and inversely correlated with mean uterine artery PI (p<0.01) BMI and height for age z scores were smaller in JIA girls than in HC. Polyarticular JIA girls and those that had received greater steroid doses had the largest chance to have short stature. There was no difference between JIA girls and HC regarding menarche age. Final height and the final height/target height difference was not different between JIA girls and HC. Conclusion: The current study showed that JIA girls from the most severe subtypes and those that had received the largest steroid cumulative doses were more susceptible to growth and puberty delays, even six months after drug withdrawal. Pelvic US was a sensitive tool in detecting sexual development in girls, being able to identify puberty delays, unsuspected by Tanner stage evaluation.

Orientador: Claudia Saad Magalhães / Banca: Silvana Brasília Sacchetti / Banca: José Eduardo Corrente / Resumo: Objetivo: Caracterizar a atividade inflamatória articular e sistêmica na Artrite Idiopática Juvenil (AIJ), determinando o estado de remissão com e sem uso de medicação. Métodos: Cento e sessenta e cinco casos de AIJ classificados segundo os critérios de 2004 da Liga Internacional de Associações de Reumatologia (ILAR), acompanhados no serviço de Reumatologia Pediátrica FMB-UNESP, entre 1986 e 2005 com uma média de seguimento de 3,6 anos, foram revisados para caracterização de episódios de inatividade, remissão clínica com e sem uso de medicação, selecionando-se aqueles com acompanhamento mínimo de 1 ano. Foram analisados os descritores dos subtipos de AIJ. A freqüência de inatividade e remissão, para a comparação entre os subtipos de artrite e dos grupos que atingiram ou não remissão foram analisados por meio de estatística descritiva, análise de sobrevida por curvas de Kaplan-Meier, comparação das curvas por teste Log Rank e a análise de regressão logística para identificação de fatores preditivos para a remissão ou persistência de atividade. Resultados: Cento e oito casos preencheram os critérios de inclusão, sendo 58,3% oligoarticular persistente, 8,3% oligoarticular estendido, 1,8% poliarticular fator reumatóide positivo (FR+), 10,2% poliarticular reumatóide negativo (FR-), 12% sistêmico, 0,9% artrite psoriásica, 4,6% artrite relacionada a entesite, e 3,7% artrite indiferenciada. Dez por cento apresentavam anticorpos antinucleares (AAN) e 7,4% apresentavam uveíte. Cinqüenta e sete pacientes apresentaram um total de 71 episódios de inatividade durante o acompanhamento, com 2,9 anos em média para cada episódio. Trinta e seis episódios (50,7%) de inatividade resultaram em remissão clínica sem medicação (RC), sendo 35% para oligoarticular persistente. A probabilidade de remissão clínica em uso de medicação em 3 anos foi... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective: To estimate the clinical remission on medication and off medication rates in Juvenile Idiopathic Arthritis (JIA) by determining the articular and systemic inflammatory activity. Methods: One hundred and sixty five cases of JIA, classified according to the 2004 International League of Associations for Rheumatology criteria, attending the Rheumatology Unit FMB-UNESP from 1986 to 2005, with median follow up 3,6 years, were reviewed for recording inactive disease, clinical remission on medication and clinical remission off medication. Cases with at least one year of regular follow up were selected. All JIA subtypes descriptors were evaluated. Inactivity and remission rates were compared by survival analyses with Kaplan-Meier curves and Log Rank test. Remission predictors and risk factors for persistent activity were identified by logistic regression analysis. Results: One hundred and eight cases met the inclusion criteria, being 58,3% persistent oligoarticular, 8,3% extended oligoarticular, 1,8% polyarticular rheumatoid factor positive (RF+), 10,2% polyarticular rheumatoid factor negative (RF-), 12% systemic, 0,9% psoriatic arthritis, 4,6% enthesitis related arthritis and 3,7% undifferentiated arthritis. Ten percent had antinuclear antibodies (ANA) and 7,4% had uveitis. Fifty-seven patients experienced a total of 71 episodes of inactive disease (ID), during the entire follow-up, with a median episode duration of 2,9 years. The patients attained inactive disease from one to four times. Thirty-six episodes (50,7%) of ID resulted in clinical remission (CR) off medication, being 35% for persistent oligoarticular. The probability of clinical remission on medication (CRM) within 3 years, was 63%, 83% and 60%, respectively for persistent oligoarticular, polyarticular and systemic arthritis cases. The probability of clinical remission... (Complete abstract click eletronic address below) / Mestre

Made available in DSpace on 2014-06-11T19:28:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-10-04Bitstream added on 2014-06-13T19:15:52Z : No. of bitstreams: 1 fernandes_tap_me_botfm.pdf: 1114659 bytes, checksum: ff36108431619df300e64aa654703f1d (MD5) / Objetivo: Caracterizar a atividade inflamatória articular e sistêmica na Artrite Idiopática Juvenil (AIJ), determinando o estado de remissão com e sem uso de medicação. Métodos: Cento e sessenta e cinco casos de AIJ classificados segundo os critérios de 2004 da Liga Internacional de Associações de Reumatologia (ILAR), acompanhados no serviço de Reumatologia Pediátrica FMB-UNESP, entre 1986 e 2005 com uma média de seguimento de 3,6 anos, foram revisados para caracterização de episódios de inatividade, remissão clínica com e sem uso de medicação, selecionando-se aqueles com acompanhamento mínimo de 1 ano. Foram analisados os descritores dos subtipos de AIJ. A freqüência de inatividade e remissão, para a comparação entre os subtipos de artrite e dos grupos que atingiram ou não remissão foram analisados por meio de estatística descritiva, análise de sobrevida por curvas de Kaplan-Meier, comparação das curvas por teste Log Rank e a análise de regressão logística para identificação de fatores preditivos para a remissão ou persistência de atividade. Resultados: Cento e oito casos preencheram os critérios de inclusão, sendo 58,3% oligoarticular persistente, 8,3% oligoarticular estendido, 1,8% poliarticular fator reumatóide positivo (FR+), 10,2% poliarticular reumatóide negativo (FR-), 12% sistêmico, 0,9% artrite psoriásica, 4,6% artrite relacionada a entesite, e 3,7% artrite indiferenciada. Dez por cento apresentavam anticorpos antinucleares (AAN) e 7,4% apresentavam uveíte. Cinqüenta e sete pacientes apresentaram um total de 71 episódios de inatividade durante o acompanhamento, com 2,9 anos em média para cada episódio. Trinta e seis episódios (50,7%) de inatividade resultaram em remissão clínica sem medicação (RC), sendo 35% para oligoarticular persistente. A probabilidade de remissão clínica em uso de medicação em 3 anos foi... / Objective: To estimate the clinical remission on medication and off medication rates in Juvenile Idiopathic Arthritis (JIA) by determining the articular and systemic inflammatory activity. Methods: One hundred and sixty five cases of JIA, classified according to the 2004 International League of Associations for Rheumatology criteria, attending the Rheumatology Unit FMB-UNESP from 1986 to 2005, with median follow up 3,6 years, were reviewed for recording inactive disease, clinical remission on medication and clinical remission off medication. Cases with at least one year of regular follow up were selected. All JIA subtypes descriptors were evaluated. Inactivity and remission rates were compared by survival analyses with Kaplan-Meier curves and Log Rank test. Remission predictors and risk factors for persistent activity were identified by logistic regression analysis. Results: One hundred and eight cases met the inclusion criteria, being 58,3% persistent oligoarticular, 8,3% extended oligoarticular, 1,8% polyarticular rheumatoid factor positive (RF+), 10,2% polyarticular rheumatoid factor negative (RF-), 12% systemic, 0,9% psoriatic arthritis, 4,6% enthesitis related arthritis and 3,7% undifferentiated arthritis. Ten percent had antinuclear antibodies (ANA) and 7,4% had uveitis. Fifty-seven patients experienced a total of 71 episodes of inactive disease (ID), during the entire follow-up, with a median episode duration of 2,9 years. The patients attained inactive disease from one to four times. Thirty-six episodes (50,7%) of ID resulted in clinical remission (CR) off medication, being 35% for persistent oligoarticular. The probability of clinical remission on medication (CRM) within 3 years, was 63%, 83% and 60%, respectively for persistent oligoarticular, polyarticular and systemic arthritis cases. The probability of clinical remission... (Complete abstract click eletronic address below)

Introduction: Idiopathic inflammatory myopathies (myositis, IIM) are heterogeneous group of rare autoimmune systemic diseases, characterized particularly by proximal skeletal muscle weakness. Heretogeneity of myositis is based on different pathogenetic mechanisms which may be reflected by variable imunophenotypic response in individual subtypes. Objectives: The aim of this work was to explore the associations and influence of soluble factors of immune system in patient's sera on phenotypic characteristics and subtypes of IIM, to describe their expression in inflammed muscle tissue and study their eventual role in pathogenesis by analysis of effect on immune and muscle cells in vitro. Results: We have described prevalence and characteristics of joint involvement in myositis patients and its significant association with anti-Jo-1 autoantibody. Further we confirmed the relation of anti-HMGCR antibody to immune mediated necrotizing myopathy, its tight relation to statins and recent increase in incidence. We showed inverse association of IFNα serum levels with muscle activity detected on MRI. Clinical activity positively correlated with IFN type-I pathway activation in patients with dermatomyositis. We also show positive correlation of resistin levels and clinical activity and correlation of activity...

Introdução: A Artrite Idiopática Juvenil (AIJ) inicia-se principalmente no intervalo etário de oito a catorze anos, podendo estar associada a déficit de crescimento e atraso puberal. O estadiamento de Tanner e a avaliação ultrassonográfica da pelve podem detectar atrasos no desenvolvimento puberal. Objetivos: Comparar a maturação sexual das meninas com AIJ a controles saudáveis, por meio da avaliação clínica dos estágios de Tanner e dos parâmetros da ultrassonografia (US) pélvica e relacionar esses achados aos níveis de hormônios sexuais e fatores relacionados à doença. Comparar, também, os dados antropométricos e a idade da menarca entre os dois grupos e relacioná-los a fatores de risco ligados à AIJ. Delineamento: Estudo transversal com grupo controle Metodologia: O estudo foi realizado com 44 meninas com AIJ e 59 controles com idades entre seis e dezoito anos incompletos, sem uso de glicocorticoides há no mínimo seis meses e sem outras doenças crônicas concomitantes. O diagnóstico de AIJ foi realizado de acordo com critérios da Liga Internacional das Associações de Reumatologia (ILAR). Foi realizada avaliação antropométrica, e a maturação sexual foi avaliada por meio dos estádios de Tanner. A US pélvica abdominal foi utilizada para avaliar as medidas do útero dos ovários e o índice de pulsatilidade das artérias uterinas (IP). Foram medidos níveis hormonais de FSH, LH, estrógeno, progesterona e IGF-1 nas meninas com AIJ. Resultados: Os parâmetros da US pélvica foram correlacionados aos estágios de Tanner no grupo controle (p <0,001). Todas as medidas de útero e ovários foram menores nas meninas com AIJ quando comparadas ao grupo controle. A média do IP das artérias uterinas foi maior nas meninas com AIJ. Estratificando-se por idade, o volume do útero foi menor nas meninas com AIJ na faixa etária de 10-11 anos (p < 0,004) e 14-15 anos (p=0,042), e a relação corpo/cérvice AP foi menor no intervalo de 10-11 anos (p=0,007). Os níveis de LH e estradiol foram fortemente relacionados ao aumento dos órgãos pélvicos (p<0,001) e inversamente com IP médio das artérias uterinas (p<0.01). O escore z do IMC e da estatura foi menor nas meninas com AIJ em relação ao grupo controle (p=0,032 e p=0,041 respectivamente). As meninas com AIJ poliarticular e com maior dose cumulativa de glicocorticoide apresentaram a maior chance de ter baixa estatura. Não houve diferença entre os grupos AIJ e controles com relação à idade da menarca. A altura final e a diferença entre essa altura e a altura-alvo familiar não foi diferente entre as meninas com AIJ e as do grupo controle. Conclusão: Nosso estudo mostrou que, mesmo sem uso de glicocorticoide há mais de seis meses, as crianças com formas mais graves de AIJ e que necessitaram de doses maiores de glicocorticoide estão mais suscetíveis ao retardo no crescimento e atraso no início da puberdade. A US pélvica demonstrou ser um exame sensível para avaliação da maturação sexual de meninas, identificando atrasos nas meninas com AIJ não percebidas por meio da avaliação clínica pelos estágios de Tanner. / Introduction: Juvenile Idiopathic Arthritis (JIA) manifests at the 8 to 14-year age span and is often associated with growth deficit and puberty delay. Tanner staging and pelvic ultrasonography (US) can be used to detect pubertal delays. Objectives: To compare sexual maturation in JIA girls and healthy controls (HC) by clinical evaluation with Tanner stages and pelvic US parameters and to correlate these findings with sexual hormone levels and disease related factors. Additionally, to compare anthropometric data and menarche age between groups and to correlate such findings with disease related risk factors in JIA patients. Study design: Cross-sectional study. Methods: 44 JIA and 59 healthy girls, aged six to 18 years, free of steroid use in the last six months and with no concomitant chronic diseases were included the study. JIA was diagnosed after the International League of the Rheumatology Associations (ILAR) criteria. Anthropometric and sexual development evaluations by Tanner staging were performed Pelvic US was performed to measure uterus, endometrial thickness, ovaries and uterine artery pulsatility index. Sexual hormone levels were measured in JIA girls. Results: Pelvic US parameters correlated with Tanner stages in HC (p <0.001). All uterine and ovarian measurements were smaller in JIA girls than in HC. Mean uterine artery PI was greater in JIA girls. Uterine volume was smaller in JIA girls at the 10 to 11 (P=0.004) and 14 to 15 year (p=0.042) age strata and the anteroposterior body cervix ratio was smaller in JIA girls the 10 to 11 year stratum (p=0.007). LH and estradiol levels were strongly correlated with pelvic organ size. (P<0.001) and inversely correlated with mean uterine artery PI (p<0.01) BMI and height for age z scores were smaller in JIA girls than in HC. Polyarticular JIA girls and those that had received greater steroid doses had the largest chance to have short stature. There was no difference between JIA girls and HC regarding menarche age. Final height and the final height/target height difference was not different between JIA girls and HC. Conclusion: The current study showed that JIA girls from the most severe subtypes and those that had received the largest steroid cumulative doses were more susceptible to growth and puberty delays, even six months after drug withdrawal. Pelvic US was a sensitive tool in detecting sexual development in girls, being able to identify puberty delays, unsuspected by Tanner stage evaluation.

Abstract Genetic factors and their resulting phenotypes were evaluated in three different bone disorders: osteogenesis imperfecta (OI), juvenile idiopathic osteoporosis (JIO), and stress fractures. The spectrum of the OI phenotypes caused by mutations in the COL1A1 and COL1A2 genes is well defined, but the mechanisms by which the variations affect the hearing phenotype are not well-known. A total of 54 Finnish OI patients with previously diagnosed hearing loss, or aged 35 or more years, were analyzed here for mutations in COL1A1, or COL1A2. Altogether, 49 mutations were identified, of which 41 were novel. No correlation was observed between the mutated gene, or the mutation type, and the hearing pattern. This indicates that the basis of hearing loss in OI is complex, and is a result of multifactorial, still unknown genetic effects, or of variable expressions of the COL1A1 and COL1A2 genes. JIO presents peri-pubertally as an acute symptomatic osteoporosis (bone pain and fractures) in otherwise healthy children, and no underlying cause has yet been identified for this disorder. Here, the analysis of the low-density lipoprotein receptor-related protein 5 gene (LRP5) in 20 patients with JIO revealed two missense mutations (A29T and R1036Q) and one frameshift mutation (C913fs) in 3 of the patients. The LRP5 gene has recently been shown to be also involved in osteoporosis-pseudoglioma syndrome and a high-bone-mass phenotype. Stress fractures are a significant problem among athletes and soldiers. Genetic factors may increase the fracture risk, but no susceptibility genes have yet been identified. Seven genes involved in bone metabolism, or pathology, were studied in terms of their roles in stress fracture. No disease-causing, or predisposing variations were found in the candidate gene, or association analyses, but a highly significant association was found between the phenotype and a vitamin D receptor (VDR) haplotype, TGT, which is composed of three polymorphic sites, FokI, BsmI and TaqI. We showed that femoral neck stress fractures are associated with a certain VDR haplotype, accounting for a five-fold increase in the risk of developing stress fractures, with an associated attributable risk of 12%. The results of this study show that genetic factors play a role in different pathological bone phenotypes. These findings provide new information on the pathogenesis of the disorders and for the development of genetic testing and targeted treatment for the disorders.

Inflammatory arthritis (IA) types such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and psoriatic arthritis (PsA) have been shown to exhibit common clinical features. As complex diseases they have a known genetic component, some of which is known to be shared. The aim of this study was to assess the genetic overlap between 3 types of IA (RA, JIA and PsA) using genotype data generated on the Immunochip array and to select a biologically promising overlapping region for further genetic and functional investigation. Overlap analysis was performed using association data generated for a large cohort of inflammatory arthritis cases and shared controls (11,475 RA; 2816 JIA; 929 PsA respectively). 50 genetic regions were identified as being associated with more than 1 type of IA (p < 1x10-3), with several interesting similarities and differences observed between the diseases. As several of the overlapping regions detected represented novel disease associations, they required replication in an independent sample cohort. 12 variants were selected for replication in an independent RA cohort of 3879 cases and 2561 controls. Of these, 2 variants in the CTLA4 and MTMR3 regions were successfully replicated in RA at p<0.05. Bioinformatics analysis was performed for the 50 overlapping regions, with one particularly promising region, RUNX1, selected for further investigation. In this region, the same variant (rs9979383) is associated across the 3 diseases, with similar odds ratios (OR 0.8-0.9) observed in each disease. As this region represented both a novel IA association and had not been densely genotyped on the Immunochip array, fine mapping was performed by genotyping 51 SNPS in 3491 cases and 2359 controls. This resulted in replication of the association at rs9979383 (p=0.02) with no additional significant genetic effects detected, therefore this variant was selected for further functional analysis. As rs9979383 lies ~280kb upstream of the RUNX1 gene, a cis-eQTL analysis was performed to identify if the variant acts by regulation of RUNX1 gene expression. This was performed in whole blood, CD4+ and CD8+ lymphocytes from 75 (and a subset of 23) healthy volunteers respectively. No significant eQTLs were detected between rs9979383 and RUNX1 in whole blood (p =0.9) or RUNX1/LOC100506403 CD4+ and CD8+ lymphocytes (p=0.1). This study has provided insight into the genetic similarities and differences between different types of inflammatory arthritis, which can be applied to further investigations into disease susceptibility. Although no significant cis-eQTL was detected in any of these tissues with either RUNX1 or the nearby lnc-RNA LOC100506403, in cells from healthy volunteers under unstimulated conditions, these findings will direct future functional investigations into the role of this overlapping region in the susceptibility of IA.

Introduction :Les rétrovirus infectieux des vertébrés sont regroupés en 7 genres : les Alpharétrovirus, les Bétarétrovirus, les Gammarétrovirus, les Deltarétrovirus, les Epsilonrétrovirus, les Lentivirus et les Spumavirus. Le Human T-cell Leukemia virus (HTLV), un deltarétrovirus, et l'Human Immunodeficiency Virus (HIV), un lentivirus, infectent l'homme. Des cas sporadiques d'infection par des spumavirus (virus Foamy) ont été décrits chez des personnes vivant en promiscuité avec des animaux infectés. Plusieurs éléments sont en faveur de l'existence de rétrovirus humains encore inconnus :-De nouvelles espèces de HTLV ont été découvertes récemment et de nombreux patients séroindéterminés compatibles avec la présence de nouvelles espèces de type HTLV ont été décrits. De plus la découverte d'un hypothétique nouveau rétrovirus le Xenotropic Murine Related retroVirus (XMRV) a recemment été discuté. De nombreuses pathologies humaines dites idiopathiques ont une symptomatologie très proche de maladies rétrovirales décrites chez les mammifères comme des maladies inflammatoires articulaires chroniques, des maladies inflammatoires des systèmes nerveux central et périphérique, des cytopénies, des syndromes myéloprolifératifs et des pathologies malignes. Une étiologie rétrovirale a, par exemple, été évoquée dans le syndrome de Kawasaki ou les anémies hémolytiques, mais sans avoir pu être formellement démontrée.-Le statut de super prédateur de l'homme rend la transmission inter-espèces possible.Toutes les recherches de nouveaux rétrovirus humains faites par le passé étaient basées sur des séquences communes à tous les rétrovirus, le gène de la polymérase ou la partie transmembranaire de la glycoprotéine d'enveloppe (Env). De ce fait, ces recherches ont été le plus souvent « parasitées » par les séquences endogènes rétrovirales ou des rétrovirus « contaminants ». Nous avons souhaité rechercher la présence de rétrovirus dans ces pathologies pédiatriques. Parallèlement, nous nous sommes intéressés aux (retro)virus pouvant se transmettre de la mère à l'enfant lors de l'allaitement. Méthode :Nous avons utilisé 2 méthodes pour rechercher des rétrovirus.1) PCR : Notre démarche cible paradoxalement la région la plus variable du génome des rétrovirus, Env, au niveau du RBD (pour Receptor-Binding Domain), domaine qui lie le récepteur d'entrée dans la cellule. Pour cela nous utilisons une méthode développée au laboratoire, basée sur des PCR dont les amorces sont constituées de courts motifs conservés, délimitant les domaines variables du RBD. Cette approche a déjà permis au laboratoire de mettre en évidence de nouveaux variants des PTLV (HTLV/STLV). Sur ce principe, nous avons ainsi conçu des amorces PCR pour la détection de RBD de deltarétrovirus bovin (Bovine Leukemia Virus) et infectant les primates (Prima T-Leukemia/Lymphoma Virus) ; de bêta rétrovirus infectant la souris (Mouse Mammary Tumor Virus) et des primates (Mason Pfizer Monkey Virus) et de gammaretrovirus infectant les félins/félidés (Feline Leukemia Virus), l'XMRV et un rétrovirus endogène porcin le PERV.2) mesure de l'activité reverse transcriptase de rétrovirus de type C au sein de liquides biologiques de patients malades. Résultats : Nous avons analysé en terme de patients 35 purpura thrombopénique immunologiques, 3 anémie hémolytique, 6 anémie arégénérative, 5 neutropénie, 1 aplasie médullaire idiopathique, 3 thrombocytose, 59 arthrite juvénile, 1 dermatomyosite, 9 purpura rhumatoïde, 4 syndrome de Kawasaki, 5 syndrome neurologique, 13 fièvre atypique, 3 leucose et 5 pathologies autres. Les recherches de rétrovirus par PCR et mesure d'activité reverse transcriptase se sont avérées négatives.Conclusion :Nous n'avons pas retrouvé de séquences rétrovirales au sein des échantillons analysés par ces deux techniques différentes. Cependant, ces résultats n'excluent pas l'hypothèse d'une étiologie rétrovirale. / The infectious mammalian retrovirus constituting seven species: Alpharetroviruses, betaretroviruses, gammaretroviruses, deltaretrovirus, epsilonretroviruses, lentiviruses and, spumaviruses. Human T-cell Leukemia virus (HTLV), a deltaretrovirus, and Human Immunodeficiency Virus (HIV), a lentivirus, infect human. Sporadic cases of spumavirus (virus Foamy) infection have been described in persons living in promiscuity with infected animals. Recent Studies have shown the presence of an hypothetic gammaretrovirus, xenotropic murine leukemia related virus (XMRV), its existence is actually discussed.There are some facts pointing to the existence of human retrovirus not yet known. -New HTLV species have been recently described and a number of sero-indeterminate patients are compatible with the presence of new HTLV species.-Many idiopathic human diseases have clinical presentation close to retroviral mammalian diseases: chronic inflammatory articular diseases, central nervous system inflammatory diseases, cytopenia, myeloproliferative syndromes and malignant pathologies. For example a retroviral aetiology have been discussed in Kawasaki syndrome and autoimmune haemolytic anemia even though a complete proof haven't been found. The super human predatory status makes the interspecies transmission possible. All the research in new human retrovirus done in the past was based in common sequencies of retroviruses like polymerase gene or the transmenbranair part of glycoprotein envelope gene (Env). Thus most of these researches have been compromise by HERV sequences or retroviral contaminants.We research retroviruses in these diseases. We also have been interested by putative (retr)viral itransmission by breast milk.Methodology1)PDR: We design primer based on the most variable region of retroviruses, the RBD (Receptor-Binding Domain), which is the domain of Env that links the cellular receptor responsible of the cellular entry. For this we used a patented method developed in our laboratory based on PCR whose primers are composed of short conservative sequences delimiting variable areas of RBD.This approach has already allowed discovering new PTLV (HTLV/STLV) variants known. As a result, we have designed PCR primers for RBD for all the known deltaretrovirus, Bovine Leukaemia Virus, (BLV) and also for the detection of gammaretrovirus feline leukaemia virus (FeLV), XMRV and Porcine Endogenous Retrovirus (PERV).2)We measure the reverse transcriptase activity to detect Type C retrovirus in body fluid.Results:We analysed in terms of patients 35 Immunologic thrombopenic purpura, 3 hemolytic anemia, 6 aregenerative anemia, 5 neutropenia, 1 aplastic anemia, 3 thrombocytosis, 59 Idiopathic juvenile arthritis, 1 dermatomyositis, 9 Henoch-Scholein diseases, 4 Kawasaki syndrome, 5 neurological diseases, 13 atypic fevers, 3 leukosis and 5 others diseases. We do not found any virus by both methodologies.We do not find viruses by PCR and reverse transcrptase activity measurment however this fact does not exclude viral etiology, further analysis could be done.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most prevalent childhood rheumatic disease and significantly impacts a child’s well-being by potentially leading to disability and long-lasting effects. It consists of all forms of arthritis developing before the age of 16, therefore managing this disease is not simple. JIA can lead to a host of different medical problems over time and requires early attention and adequate treatment to prevent these long-term consequences. However, many children still experience pain after traditional treatment, indicating a need for alternative treatment modalities. Exercise therapy is one form of treatment that can potentially enhance a child’s quality of life. LITERATURE REVIEW FINDINGS: Multiple forms of exercise therapy have been shown to improve quality of life, functional ability and pain in patients with JIA. Exercise does not worsen disease activity, including the number of joints affected. While there are a limited number of studies in the JIA population, studies on patients with rheumatoid arthritis, a rheumatic disease diagnosed in adulthood, demonstrate the potential for exercise therapy to alter the pathophysiology of the disease and lead to better immune function. Exercise may have the ability to affect children with JIA in the same way as the two diseases share a similar pathophysiology. PROPOSED PROJECT: The goal of the proposed randomized control trial is to measure the impact of an exercise intervention on the quality of life of children with JIA, the effect exercise on participant immune function and variations in response between each subtype of JIA. Children will either complete high intensity interval walking training three times a week or no exercise intervention for 10 weeks. Various outcomes including quality of life, functional status, pain and fitness level will be measured before and after the intervention. Blood analysis to assess changes in immune function and further analysis between subtypes will also be conducted. CONCLUSIONS: The use of exercise therapy as a management tool for JIA should be considered earlier on in the disease course. It has not been found to worsen the disease and has produced increases in quality of life, functional status and pain. The benefits of this therapy are widespread and are not limited to healthy individuals. SIGNIFICANCE: This will be the first time these analyses will be performed and, if improvement is seen, this could help guide a physician’s disease management plan. Data from this study could provide information on how exercise modifies the disease and how to design more structured exercise programs appropriate to each subtype of JIA. Exercise may begin to be incorporated into the treatment plan for these children to increase disease remission rates, reduce the amount and severity of disease flares and provide both physical and psychological benefits.

Introduction: Idiopathic inflammatory myopathies (myositis, IIM) are heterogeneous group of rare autoimmune systemic diseases, characterized particularly by proximal skeletal muscle weakness. Heretogeneity of myositis is based on different pathogenetic mechanisms which may be reflected by variable imunophenotypic response in individual subtypes. Objectives: The aim of this work was to explore the associations and influence of soluble factors of immune system in patient's sera on phenotypic characteristics and subtypes of IIM, to describe their expression in inflammed muscle tissue and study their eventual role in pathogenesis by analysis of effect on immune and muscle cells in vitro. Results: We have described prevalence and characteristics of joint involvement in myositis patients and its significant association with anti-Jo-1 autoantibody. Further we confirmed the relation of anti-HMGCR antibody to immune mediated necrotizing myopathy, its tight relation to statins and recent increase in incidence. We showed inverse association of IFNα serum levels with muscle activity detected on MRI. Clinical activity positively correlated with IFN type-I pathway activation in patients with dermatomyositis. We also show positive correlation of resistin levels and clinical activity and correlation of activity...