RESUMO A artrite reumatoide (AR) é uma doença reumática inflamatória autoimune que afeta vários órgãos e tecidos, predominantemente as articulações sinoviais. Como muitas outras doenças autoimunes, a AR é uma doença complexa, em que variantes genéticas, fatores ambientais e eventos aleatórios interagem e desencadeiam vias patológicas. A implicação genética na AR é evidente e avanços recentes têm expandido nosso conhecimento sobre os fatores genéticos que contribuem para a doença. Houve um incremento exponencial na quantidade de genes associados à doença descritos, principalmente por estudos de associação genômica ampla (GWAS) que envolveram consórcios internacionais com grandes grupos de pacientes. No entanto, há poucos estudos em populações latino-americanas. Este artigo descreve o que é conhecido sobre a genética na AR, o que vem a seguir e como isso vai desenvolver uma abordagem mais personalizada para o tratamento da doença. Os pacientes latino-americanos com AR não podem ser excluídos desse objetivo final e pode ser necessária uma maior colaboração com os consórcios internacionais para se obter um melhor conhecimento do perfil genético dos pacientes provenientes dessa região.

ABSTRACT Rheumatoid Arthritis (RA) is an autoimmune inflammatory rheumatic disease which affects several organs and tissue, predominantly the synovial joints. Like many other autoimmune diseases, RA is a complex disease, where genetic variants, environmental factors and random events interact to trigger pathological pathways. Genetic implication in RA is evident, and recent advances have expanded our knowledge about the genetic factors that contribute to RA. An exponential increment in the number of genes associated with the disease has been described, mainly through gene wide screen studies (GWAS) involving international consortia with large patient cohorts. However, there are a few studies on Latin American populations. This article describes what is known about the RA genetics, the future that is emerging, and how this will develop a more personalized approach for the treatment of the disease. Latin American RA patients cannot be excluded from this final aim, and a higher collaboration with the international consortia may be needed for a better knowledge of the genetic profile of patients from this origin.

Inflammatory bowel disease (IBD) is an entity that mainly includes ulcerative colitis (UC) and Crohn's disease (CD). Improved health care, diet changes, and higher industrialization are associated with an increase in IBD prevalence. This supports the central role of environmental factors in the pathology of this disease. However, IBD also shows a relevant genetic component as shown by high heritability. Classic genetic studies showed relevant associations between IBD susceptibility and genes involved in the immune response. This is consistent with prior theories about IBD development. According to these, contact of the immune system with a high number of harmless antigens from the diet and the bacterial flora should originate tolerance while preserving response against pathogens. Failure to achieve this balance may originate the typical inflammatory response associated with IBD. Recently, genome-wide association studies (GWASs) have confirmed the implication of the immune system, particularly the Th17 immune response, previously associated to other autoimmune diseases, and of autophagy. In this paper, the mechanisms involved in these two relevant pathways and their potential role in the pathogenesis of IBD are reviewed.

La enfermedad inflamatoria intestinal (EII) es una entidad que engloba principalmente a la colitis ulcerosa (CU) y la enfermedad de Crohn (EC). Las mejoras sanitarias, cambios en la alimentación y una mayor industrialización se han asociado con mayor prevalencia de EII lo que demuestra la gran importancia de diferentes factores ambientales en la etiopatogenia de esta patología. Sin embargo, la EII presenta al mismo tiempo un importante componente genético según demuestra su alta heredabilidad. Los estudios genéticos clásicos mostraron asociaciones con genes implicados en la respuesta inmune, consecuentes con las teorías expuestas sobre el desarrollo de la enfermedad en las que el contacto del sistema inmune del sistema digestivo con gran número de antígenos inocuos de la flora y de la dieta debe originar tolerancia, manteniendo al mismo tiempo la respuesta frente a los patógenos. Un desequilibrio en este sistema originaría la respuesta inflamatoria típica de la EII. Recientemente, estudios de asociación de genoma completo (GWAS) han confirmado esta implicación del sistema inmune, particularmente de la respuesta inmune Th17, relacionada también con otras patologías autoinmunes. Otro proceso fuertemente implicado por estos estudios es el de la autofagia. En este artículo se revisan los mecanismos involucrados en estas dos vías y su posible relación con la patogenia de la EII.

The process of malignancy emergence is associated with the acquisition of the capacity to invade other tissues. Several different biological processes have been described as involved in this process. Specifically, epithelial mesenchymal transition (EMT), a mechanism associated with embryogenesis and wound repair but also with mobility acquisition, is one of the concerned processes. In EMT an epithelial cell loses its epithelial characteristics, its junctions with neighbor cells and with the basal lamina and acquires mobility and mesenchymal characteristics. Also, factors of the tumor microenvironment have been described as involved. Tumor presence triggers a response in the surrounding tissue known as reactive stromal. It shows particular characteristics similar to those found in wound healing stroma: an increase of the fibroblast number and enhancing of the capillary density. The notable difference is the chronicity in the tumoral process. Of a high relevance seems to be the role of activated macrophages with a characteristic phenotype. Finally, cancer associated fibroblasts (CAF) are a type of cells found in tumors, developed from local tissue or possibly from bone marrow. CAF characteristically show a distinct morphology and secrete a high number of metalloproteases allowing tumoral cells advance through the tissue. Additionally, CAF have a direct effect on the survival of the epithelial cells. The three processes are interrelated and metastasis is probably caused by the effect of all of them and probably by other additional factors.

El desarrollo de malignidad está asociado con la adquisición de la capacidad de invadir otros tejidos. Varios procesos diferentes han sido asociados con la aparición de metástasis. Concretamente, la transición epitelio mesénquima (TEM), un mecanismo asociado con embriogénesis y reparación de heridas pero también con adquisición de movilidad, es uno de ellos. En la TEM, una célula epitelial pierde sus características epiteliales, sus uniones con las células vecinas y con la lámina basal y adquiere movilidad y características mesenquemáticas. También han sido asociados factores del microambiente del tumor. La presencia del tumor produce una respuesta en el tejido que lo rodea descrito como estroma reactivo. Sus características son similares a las del estroma de las heridas en proceso de curación: un incremento del número de fibroblastos y un aumento de la densidad de capilares. La gran diferencia es la cronicidad del proceso tumoral. De gran relevancia es el papel de los macrófagos activados que muestran un fenotipo característico. Finalmente, los fibroblastos asociados a cáncer (FAC) son un tipo de células encontradas en tumores, que se desarrollan a partir del tejido local o quizá de la médula ósea. Los FAC, de modo característico muestran una morfología diferente y secretan una gran cantidad de metaloproteasas permitiendo a la célula tumoral avanzar a través del tejido. Además, los FAC ejercen un efecto directo sobre la supervivencia de las células epiteliales. Los tres procesos están interrelacionados y la metástasis es causada probablemente por el efecto de todos ellos y probablemente por otros factores adicionales.

Ankylosing spondylitis (AS) is a prototypical inflammatory disease of the locomotor system affecting axial skeleton. It is part of the general group of spondyloarthopathies (SpA). Its strong association with histocompatibility antigen HLA-B27 is known since 1973. However, HLA-B27 contribution to AS genetic risk is approximately 16%. Therefore, other genes are necessarily involved in the pathogenesis of the disease. Genomic development and the possibility of making genome wide screening have contributed enormously to the study of the disease. In this paper, we describe the actual knowledge about AS genetic risk, which has contributed to understand the influence of HLA-B27 on the etiology and pathogenesis of the disease. We also intend to foresee how these findings will result in an improvement of patients’ quality of life.