Whiplash is a neck injury caused by the sudden differential movement between the head and torso. Whiplash injuries are most commonly reported as a consequence of rear impacts in car accidents. They are regarded as minor injuries, but can still lead to long-term disablement and discomfort in the neck. Whiplash injuries can be mitigated by better car seat designs. For this purpose, head restraint geometry must be improved first, and then the dynamic performance of the whole seat must be assessed at all crash seventies. A biofidelic human-body model is a key requirement in designing whiplash mitigating car seats. This thesis presents the development of a 50th percentile male multi-body human model and several energy absorbing car seat designs. The human-body model is specifically designed for rear impact and validated using the responses of seven volunteers from Japanese Automobile Research Institute (JARI) sled tests, which were performed at an impact speed of 8 kph with a rigid seat and without head restraint and seat belt. A generic multi-body car seat model is also developed to implement various seatback and recliner properties, anti-whiplash devices (A WDs) and head restraints. Using the same driving posture and the rigid seat in the JARI sled tests as the basic configuration, several anti-whiplash seats are designed to allow different types of motion for the seatback and seat-pan. The major findings of this research are: -The human-body model simulates the effects of muscle contraction and its overall response is superior in comparison to the currently used models and dummies. -A criterion called the S-shape index (SSI) is developed based on the intervertebral angles of the upper and lower cervical spine. -The car seat design concepts are able to control and use crash energy effectively with the aid of anti-whiplash devices for a wide range of crash seventies. -In order to reduce whiplash injury risk, this study advocates energy absorbing car seats which can also provide head restraint contact as early as possible.

Le lupus érythémateux disseminé (LED) est une maladie chronique auto-immune caractérisée par la production d'autoanticorps dirigés contre les antigènes nucléaires. Des nombreuses études indiquent un rôle des récepteurs Toll-like (TLR). Des études antérieures de notre laboratoire ont révélé que le TLR8 murin contrôle la fonction de TLR7 dans les cellules dendritiques et est aussi impliqué dans le lupus. TLR9 contrôle également le lupus dépendant de TLR7. Mon projet de thèse avait deux objectifs dont le premier était de comprendre comment le TLR8 et TLR9 contribuent au lupus dépendant de TLR7. En outre, nous avons révélé que TLR8 contrôle l'expression de TLR7 dans les cellules dendritiques, tandis que le TLR9 contrôle la fonction de TLR7 dans les cellules B. Le deuxième objectif était d'étudier l'implication du répresseur transcriptionnel Gfi-1 dans la signalisation des TLR et le développement de lupus en utilisant des souris Genista qui portent une mutation ponctuelle dans le gène Gfi-1. Nous avons constaté que les souris Genista développent un lupus dépendant de TLR7 et que Gfi-1 agit comme un répresseur de la transcription en aval de TLR7 et contrôle l'expression d'Interféron de type I dépendante des TLR. Ainsi, le déséquilibre des interactions entre TLR ainsi que les facteurs transcriptionnels en aval de ces TLR peuvent conduire à des mécanismes d'inflammation et d'auto-immunité qu'il est important de prendre en compte dans le développement d'approches thérapeutiques nouvelles ciblant les TLRs. / Systemic lupus erythematosus is a chronic autoimmune disease characterized by production of autoantibodies against nuclear antigens. Many studies indicate a role for Toll-like receptors (TLRs) in the initiation and establishment of systemic lupus erythematosus (SLE). Previous studies in the lab revealed that murine TLR8 controls TLR7 function in dendritic cells (DCs) and is implicated in SLE. TLR9 also controls TLR7-mediated lupus. My thesis had two aims: the first was to understand how the cooperation of TLR8 and TLR9 contributes to TLR7-mediated lupus. By studying double TLR8/9-deficient mice we found that TLR8 and TLR9 have an additive effect on controlling TLR7-mediated lupus, where TLR8 controls TLR7 function on DCs, while TLR9 restrains TLR7 responses in B cells. The second aim of my thesis was to investigate the implication of Gfi-1 in lupus and TLR signaling by studying Genista mice that carry a hypomorphic mutation of Gfi-1. We found that Genista mice develop TLR7-dependent lupus and that Gfi-1 acts as a transcriptional repressor downstream of TLR7 and controls type-I IFN expression. Thus, unbalancing TLR-interactions and transcription factors downstream of TLRs can lead to inflammation and autoimmunity and these mechanisms have to be taken into account when novel therapeutic approaches are developed that target TLRs.

O genoma humano varia entre os indivíduos não somente na forma de sequência, mas também estruturalmente. Originalmente, organismos diploides possuem duas cópias de cada região autossômica, uma por cromossomo. Entretanto, com o avanço das técnicas moleculares de identificação do DNA, foram descritas sequências que se repetem em diferentes regiões do genoma em número maior ou menor do que as duas cópias esperadas. Essas variantes são denominadas copy number variants (CNVs) e definidas como segmentos genômicos, geralmente maiores do que 1 kilobase (kb), que variam em número de cópias em comparação com o genoma de referência. As CNVs podem contribuir para a variabilidade do risco entre os indivíduos na etiologia de doenças complexas. Nesse contexto, o Lúpus Eritematoso Sistêmico (LES) é uma doença autoimune com forte componente genético, caracterizada por inflamação crônica e produção de autoanticorpos. Estudos de associação genômica em larga escala (GWAS) identificaram vários loci associados ao LES que contribuem para a susceptibilidade à patogênese. Entretanto, as pesquisas atuais com CNVs e LES focalizam apenas a análise individual de algumas variantes. O objetivo do presente trabalho foi conduzir o primeiro estudo de CNVs em larga escala em pacientes com LES. A detecção de CNVs foi feita por ensaio de Hibridação Genômica em arrays, utilizando a plataforma Affymetrix GeneChip® CytoScan HD em amostra de 23 pacientes com LES. Foram identificadas 406 CNVs distribuídas em todos os cromossomos, exceto no Y. A média foi de 18 CNVs por paciente. As deleções foram mais frequentes do que as duplicações, 311 e 95, respectivamente. O perfil de CNVs revelou 269 CNVs envolvendo genes, 152 CNVs únicas e 59 regiões de CNVs (CNVRs). Nove CNVs identificadas não haviam sido descritas em bancos de dados de variantes estruturais. Adicionalmente, encontramos CNVs em cinco genes previamente associados com LES: CFHR4, CFHR5, STAT4, MECP2 e HLA-DPB2. CNVs nestes genes foram reportadas em pacientes com LES pela primeira vez. O conhecimento das CNVs associadas com LES e autoimunidade podem contribuir para o entendimento da etiologia da doença. Em conclusão, o presente estudo foi o primeiro delineamento em larga escala de CNVs do genoma completo em pacientes com LES. / The human genome varies between individuals not only at the sequence level but also structurally. Originally, diploid organisms have two copies of each autosomal region, one per chromosome. Advances in molecular-based techniques for DNA identification enabled the description of many repeated sequences with higher or lower copy number than that two copies expected. Those sequences are termed copy number variants (CNVs) and are defined as genomic segments, usually greater than 1 kilobase (kb) in size, ranging in copy number when compared to reference genome. CNVs can contribute to risk variability among individuals in complex diseases etiology. In this context, Systemic Lupus Erythematosus (SLE) is an autoimmune disease with strong genetic component and is characterized by chronic inflammation and autoantibodies production. To date, genome-wide association studies (GWAS) have identified several loci associated with SLE that contribute to pathogenesis susceptibility. However, current CNVs studies associated with SLE focus only in few variants analysis. The aim of the present study was to conduct the first genome-wide CNVs study in SLE patients. CNVs detection was performed by high-resolution array Genomic Hybridization Assay, using the Affymetrix GeneChip® CytoScan HD platform, in 23 SLE patients samples. We identified 406 CNVs distributed in all chromosomes, except Y. The average was 18 CNVs per patient. Deletions were more frequent than duplications, 311 and 95, respectively. CNV profile showed 269 CNVs overlapped by genes, 152 unique CNVs and 59 CNV regions (CNVRs). Nine CNVs were never described in structural variants databases. We found CNVs in five genes previously associated with SLE: CFHR4, CFHR5, STAT4, MECP2 and HLA-DPB2. CNVs in these genes were reported in SLE patients for the first time. Knowledge of CNVs associated with SLE risk and autoimmunity could also improve our understanding of disease etiology. In conclusion, the present study was the first effort to search for CNVs in whole genome of SLE patients.

Introdução: O Lúpus eritematoso sistêmico (LES) é uma doença inflamatória autoimune crônica de etiologia ainda pouco conhecida, e de natureza pleomórfica, que intercala períodos de atividade e remissão. O desenvolvimento da autoimunidade no LES está associado à perda da tolerância imunológica e do controle imunorregulatório, tendo seus achados clínicos e laboratoriais variados. A atividade do LES pode ser medida pelo SLEDAI (systemic lupus erythematosus disease activity index) que é uma ferramenta complexa e que exige treinamento e conhecimento para sua aplicação. O volume plaquetário médio (VPM) é um marcador de ativação de plaquetas associado à inflamação, o que o torna um potencial candidato para a avaliação de atividade de doença no LES. Objetivos: Avaliar o VPM em pacientes com LES e comparar com indivíduos hígidos. Estudar a correlação entre o VPM e o índice de atividade de doença (SLEDAI) nos pacientes com LES. Analisar a correlação entre o VPM e a velocidade de sedimentação globular (VSG), a proteína C reativa (PCR), e os componentes do complemento C3 e C4 Métodos: Estudo transversal no qual foram incluídos 81 pacientes com LES segundo critérios de classificação diagnóstica do American College of Rheumatology (ACR), e 58 controles hígidos. Os pacientes foram selecionados consecutivamente por conveniência, de acordo com exames laboratoriais e SLEDAI devidamente calculados. As coletas foram realizadas entre outubro de 2015 e julho de 2016. LES ativo foi definido como SLEDAI>0 no momento da coleta. O VPM foi analisado no equipamento de automação Sysmex XE 5000. Resultados: O VPM estava reduzido nos pacientes com LES em atividade, quando comparado ao grupo de pacientes com LES inativo (10,0±0,7fL vs. 10,7±1,0fL, p=0,005). Existe uma fraca correlação inversa entre o valor do SLEDAI e o VPM (r=-0,29, p=0,009). Houve uma diferença significativa no VPM entre o grupo dos controles e os pacientes com LES ativo / Background Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune chronic disease etiology still unknown, and pleomorphic nature, which intersperses periods of activity and remission. The development of autoimmunity in SLE is related to loss of immunological tolerance and immunoregulatory control and clinical symptoms can be varied. The SLE activity can be measured by SLEDAI (systemic lupus erythematosus disease activity) which is a complex tool and it requires time and knowledge for your application. The MPV (mean platelet volume) is a marker of platelet activation and has been shown to be associated with inflammation, which makes it a potential candidate for use in the assessment of disease activity in SLE. In this study, we evaluated the MPV (Mean platelet volume) in healthy individuals and compared with SLE patients and correlate with SLEDAI VPM. Objectives: -To evaluate the MPV in SLE patients and compared with healthy individuals; to study the correlation between MPV and the SLEDAI patients with SLE and assess a possible correlation between MPV with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement 3 (C3), and complement 4 (C4) Methods: This is a cross-sectional study in which 81 patients with SLE according to the American College of Rheumatology (ACR) diagnostic classification criteria and 58 healthy controls were included. Patients were selected for convenience, according to laboratory tests and SLEDAI duly calculated. The collections were carried out between October 2015 and July 2016. Active LES was defined as SLEDAI>0 at the time of collection. The VPM was analyzed in the Sysmex XE 5000 automation equipment. Results: In this study in patients with active SLE, the MPV is reduced when compared to the group of patients with inactive SLE [10.0±0.7fL vs. 10.7±1.0fL, p=0.005]. There is a weak inverse correlation between the SLEDAI value and the MPV (r=-0.29, p=0.009). There was a significant difference between the control group and the patients with active SLE (10.9 ±1.0fL vs. 10.0±0.7fL, p <0.001). In contrast, the MPV was similar between the control group and the group of patients with inactive SLE (10.9±1.0fLvs10.7±1.0fL, p=0.40). There was no correlation between MVP and CRP, ESR, C3 and C4. Conclusion: MPV is decreased in patients with active SLE and inversely correlated with SLEDAI. Despite the difference between MVP values, between active and inactive SLE patients, the results may not be clinically relevant. Prospective longitudinal studies are needed to better characterize the fluctuation of MPV in different states of disease activity to more clearly define the role of MPV in SLE.

<p>Autoimmune mechanisms and genetic susceptibility contribute to the pathogenesis of primary Sjögren’s syndrome and SLE. These chronic systemic autoimmune diseases have many serological and clinical features in common and have an impact on daily life. The studies in this thesis aim to elucidate their autoimmune mechanisms, define susceptibility genes and evaluate effects of androgen supplement on health-related quality of life.</p><p>Autoantibodies against α-fodrin, a widely distributed cytoskeletal protein, were detected at similar frequencies in sera from patients with primary and secondary Sjögren’s syndrome and SLE. Consequently, testing for antibodies against α-fodrin would not add diagnostic value compared to conventional serological analysis and does not discriminate between these diseases.</p><p>The type I interferon (IFN) system was found to be activated in primary Sjögren’s syndrome. IFN-α containing cells were detected in minor salivary gland biopsies, while sera from patients with primary Sjögren’s syndrome induced IFN-α production in the presence of apoptotic and necrotic cell material. This ability of sera correlated with the presence of antibodies against RNA-binding proteins and IFN-α production was dependent on RNA in immune complexes. The natural interferon producing cells/plasmacytoid dendritic cells (NIPC/PDC) were the IFN-α producers and blocking of FcγRIIa inhibited the production. Single nucleotide polymorphisms (SNPs) in two genes in the type I IFN signalling pathway, those for tyrosine kinase 2 and interferon regulatory factor 5, were strongly associated with SLE in a Swedish, Finnish and Icelandic population. The minor allele frequencies were lower in SLE patients than in healthy controls. These SNPs may decrease the function of the type I IFN system, thereby conferring protection against SLE. </p><p>Supplementation with dehydroepiandrosterone (DHEA) in glucocorticoid treated women with SLE led to mild improvements in health-related quality of life in respect of mental well-being and sexuality, whereas physical well-being was unaffected.</p>

Autoimmune mechanisms and genetic susceptibility contribute to the pathogenesis of primary Sjögren’s syndrome and SLE. These chronic systemic autoimmune diseases have many serological and clinical features in common and have an impact on daily life. The studies in this thesis aim to elucidate their autoimmune mechanisms, define susceptibility genes and evaluate effects of androgen supplement on health-related quality of life. Autoantibodies against α-fodrin, a widely distributed cytoskeletal protein, were detected at similar frequencies in sera from patients with primary and secondary Sjögren’s syndrome and SLE. Consequently, testing for antibodies against α-fodrin would not add diagnostic value compared to conventional serological analysis and does not discriminate between these diseases. The type I interferon (IFN) system was found to be activated in primary Sjögren’s syndrome. IFN-α containing cells were detected in minor salivary gland biopsies, while sera from patients with primary Sjögren’s syndrome induced IFN-α production in the presence of apoptotic and necrotic cell material. This ability of sera correlated with the presence of antibodies against RNA-binding proteins and IFN-α production was dependent on RNA in immune complexes. The natural interferon producing cells/plasmacytoid dendritic cells (NIPC/PDC) were the IFN-α producers and blocking of FcγRIIa inhibited the production. Single nucleotide polymorphisms (SNPs) in two genes in the type I IFN signalling pathway, those for tyrosine kinase 2 and interferon regulatory factor 5, were strongly associated with SLE in a Swedish, Finnish and Icelandic population. The minor allele frequencies were lower in SLE patients than in healthy controls. These SNPs may decrease the function of the type I IFN system, thereby conferring protection against SLE. Supplementation with dehydroepiandrosterone (DHEA) in glucocorticoid treated women with SLE led to mild improvements in health-related quality of life in respect of mental well-being and sexuality, whereas physical well-being was unaffected.

Dans cette thèse nous proposons and nous mettons en application plusieurs modèles décrivant le croissance et la morphologie du tissu urban. Le premier de ces modèles est issu de la percolation en gradient (correlée) déjà proposé de la littérature. Le second, inédit, fait appel à un équation différentielle stochastique. Nos modèles sont paramétrisables: les paramètres que nous avons choisi d'appliquer sont naturels et tiennent compte de l'accessibilité des sites. Le résultat des simulations est conforme à la réalité du terrain. Par ailleurs, nous étudions la percolation en gradient: nous démontrons , suivant Nolin, que la frontière de cluster principal se situe dans un voisinage de la courbe critique et nous estimons ses longueurs et largeurs. Enfin, nous menons une étude du processus de croissance SLE. Nous calculons (preuve assistée par ordinateur) l'espérance des carrés des modules pour SLE_2 and SLE_6. Ces résultats sont liés à la conjecture de Bieberbach.

Cette thèse porte sur les relations entre les processus SLE, les ensembles CLE et le champ libre Gaussien. Dans le chapitre 2, nous donnons une construction des processus SLE(k,r) à partir des boucles des CLE(k) et d'échantillons de restriction chordale. Sheffield et Werner ont prouvé que les CLE(k) peuvent être construits à partir des processus d'exploration symétriques des SLE(k,r).Nous montrons dans le chapitre 3 que la configuration des boucles construites à partir du processus d'exploration asymétrique des SLE(k,k-6) donne la même loi CLE(k). Le processus SLE(4) peut être considéré comme les lignes de niveau du champ libre Gaussien et l'ensemble CLE(4) correspond à la collection des lignes de niveau de ce champ libre Gaussien. Dans la deuxième partie du chapitre 3, nous définissons un paramètre de temps invariant conforme pour chaque boucle appartenant à CLE(4) et nous donnons ensuite dans le chapitre 4 un couplage entre le champ libre Gaussien et l'ensemble CLE(4) à l'aide du paramètre de temps. Les processus SLE(k) peuvent être considérés comme les lignes de flot du champ libre Gaussien. Nous explicitons la dimension de Hausdorff de l'intersection de deux lignes de flot du champ libre Gaussien. Cela nous permet d'obtenir la dimension de l'ensemble des points de coupure et des points doubles de la courbe SLE, voir le chapitre 5. Dans le chapitre 6, nous définissons la mesure de restriction radiale, prouvons la caractérisation de ces mesures, et montrons la condition nécessaire et suffisante de l'existence des mesures de restriction radiale.

Introdução: O Lúpus eritematoso sistêmico (LES) é uma doença inflamatória autoimune crônica de etiologia ainda pouco conhecida, e de natureza pleomórfica, que intercala períodos de atividade e remissão. O desenvolvimento da autoimunidade no LES está associado à perda da tolerância imunológica e do controle imunorregulatório, tendo seus achados clínicos e laboratoriais variados. A atividade do LES pode ser medida pelo SLEDAI (systemic lupus erythematosus disease activity index) que é uma ferramenta complexa e que exige treinamento e conhecimento para sua aplicação. O volume plaquetário médio (VPM) é um marcador de ativação de plaquetas associado à inflamação, o que o torna um potencial candidato para a avaliação de atividade de doença no LES. Objetivos: Avaliar o VPM em pacientes com LES e comparar com indivíduos hígidos. Estudar a correlação entre o VPM e o índice de atividade de doença (SLEDAI) nos pacientes com LES. Analisar a correlação entre o VPM e a velocidade de sedimentação globular (VSG), a proteína C reativa (PCR), e os componentes do complemento C3 e C4 Métodos: Estudo transversal no qual foram incluídos 81 pacientes com LES segundo critérios de classificação diagnóstica do American College of Rheumatology (ACR), e 58 controles hígidos. Os pacientes foram selecionados consecutivamente por conveniência, de acordo com exames laboratoriais e SLEDAI devidamente calculados. As coletas foram realizadas entre outubro de 2015 e julho de 2016. LES ativo foi definido como SLEDAI>0 no momento da coleta. O VPM foi analisado no equipamento de automação Sysmex XE 5000. Resultados: O VPM estava reduzido nos pacientes com LES em atividade, quando comparado ao grupo de pacientes com LES inativo (10,0±0,7fL vs. 10,7±1,0fL, p=0,005). Existe uma fraca correlação inversa entre o valor do SLEDAI e o VPM (r=-0,29, p=0,009). Houve uma diferença significativa no VPM entre o grupo dos controles e os pacientes com LES ativo / Background Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune chronic disease etiology still unknown, and pleomorphic nature, which intersperses periods of activity and remission. The development of autoimmunity in SLE is related to loss of immunological tolerance and immunoregulatory control and clinical symptoms can be varied. The SLE activity can be measured by SLEDAI (systemic lupus erythematosus disease activity) which is a complex tool and it requires time and knowledge for your application. The MPV (mean platelet volume) is a marker of platelet activation and has been shown to be associated with inflammation, which makes it a potential candidate for use in the assessment of disease activity in SLE. In this study, we evaluated the MPV (Mean platelet volume) in healthy individuals and compared with SLE patients and correlate with SLEDAI VPM. Objectives: -To evaluate the MPV in SLE patients and compared with healthy individuals; to study the correlation between MPV and the SLEDAI patients with SLE and assess a possible correlation between MPV with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement 3 (C3), and complement 4 (C4) Methods: This is a cross-sectional study in which 81 patients with SLE according to the American College of Rheumatology (ACR) diagnostic classification criteria and 58 healthy controls were included. Patients were selected for convenience, according to laboratory tests and SLEDAI duly calculated. The collections were carried out between October 2015 and July 2016. Active LES was defined as SLEDAI>0 at the time of collection. The VPM was analyzed in the Sysmex XE 5000 automation equipment. Results: In this study in patients with active SLE, the MPV is reduced when compared to the group of patients with inactive SLE [10.0±0.7fL vs. 10.7±1.0fL, p=0.005]. There is a weak inverse correlation between the SLEDAI value and the MPV (r=-0.29, p=0.009). There was a significant difference between the control group and the patients with active SLE (10.9 ±1.0fL vs. 10.0±0.7fL, p <0.001). In contrast, the MPV was similar between the control group and the group of patients with inactive SLE (10.9±1.0fLvs10.7±1.0fL, p=0.40). There was no correlation between MVP and CRP, ESR, C3 and C4. Conclusion: MPV is decreased in patients with active SLE and inversely correlated with SLEDAI. Despite the difference between MVP values, between active and inactive SLE patients, the results may not be clinically relevant. Prospective longitudinal studies are needed to better characterize the fluctuation of MPV in different states of disease activity to more clearly define the role of MPV in SLE.

Made available in DSpace on 2014-12-17T14:03:45Z (GMT). No. of bitstreams: 1 OliviaMNS.pdf: 1791724 bytes, checksum: ee4754a0285c7794728cf70013277cc2 (MD5) Previous issue date: 2006-10-03 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The aetiology of autoimmunes disease is multifactorial and involves interactions among environmental, hormonal and genetic factors. Many different genes may contribute to autoimmunes disease susceptibility. The major histocompatibility complex (MHC) genes have been extensively studied, however many non-polymorphic MHC genes have also been reported to contribute to autoimmune diseases susceptibility. The aim of the present study was to evaluate the influence of SLC11A1 gene in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Ninety-six patients with SLE, 37 with RA and 202 controls enrolled in this case-control study, were evaluated with regard to demographic, genetic, laboratorial and clinical data. SLE mainly affects females in the ratio of 18 women for each man, 88,3% of the patients aged from 15 to 45 years old and it occurs with similar frequency in whites and mulattos. The rate of RA between women and men was 11:1, with 77,1% of the cases occurring from 31 to 60 years. The genetic analysis of the point mutation -236 of the SLC11A1 gene by SSCP did not show significant differences between alleles/genotypes in patients with SLE or RA when compared to controls. The most frequent clinical manifestations in patients with SLE were cutaneous (87%) and joint (84.9%). In patients with RA, the most frequent out-joint clinical manifestation were rheumatoid nodules (13,5%). Antinuclear antibodies were present in 100% of the patients with SLE. There was no significant relation between activity of disease and presence of rheumatoid factor in patients with RA, however 55,6% of patients with active disease presented positive rheumatoid factor. Significant association between alleles/genotypes of point mutation -236 and clinical manifestations was not found / A etiologia das doen?as autoimunes ? multifatorial, resultando de intera??es complexas de fatores ambientais, hormonais e gen?ticos. Diversos genes contribuem para a suscetibilidade ?s doen?as autoimunes. Os genes do complexo principal de histocompatibilidade (MHC) tem sido amplamente estudados, por?m genes n?o-MHC tamb?m parecem contribuir para a suscetibilidade a autoimunidade. O presente estudo tem por objetivo avaliar a influ?ncia do gene SLC11A1 nas doen?as autoimunes lupus eritematoso sist?mico (LES) e artrite reumat?ide (AR). Foram arrolados 96 pacientes com LES, 37 com AR e 202 controles saud?veis, em estudo caso-controle, avaliando os dados demogr?ficos, gen?ticos e cl?nico-laboratoriais. LES afetou principalmente o sexo feminino na raz?o de 18 mulheres para 1 homem, sendo 88,3% na faixa et?ria entre 15 e 45 anos e ocorreu com freq??ncias semelhantes em brancos e pardos. A raz?o encontrada de AR entre mulheres e homens foi 11:1, com 77,1% dos casos ocorrendo entre 31 e 60 anos. A an?lise gen?tica do ponto de muta??o -236 da regi?o promotora do gene SLC11A1 por SSCP, n?o mostrou diferen?as significativas entre as freq??ncias de alelos ou gen?tipos de pacientes com LES ou AR em rela??o aos controles. As manifesta??es cl?nicas mais freq?entes nos pacientes com LES foram a cut?nea (87%) e articular (84,9%). Na AR a manifesta??o cl?nica extra-articular mais encontrada foi a presen?a de n?dulo reumat?ide (13,5%). A pesquisa do anticorpo anti-nuclear (FAN) foi positiva em 100% dos pacientes com LES. N?o houve rela??o significativa entre doen?a ativa e presen?a de fator reumat?ide em pacientes com AR, no entanto, 55,6% dos pacientes com doen?a ativa, apresentavam fator reumat?ide positivo. N?o foi encontrada associa??o significativa entre as manifesta??es cl?nicas ou achados laboratoriais e alelos/gen?tipos do ponto de muta??o -236