Immunology of autoimmune diseases

Autoimmune diseases (AIDs) are a group of conditions characterized by the loss of immune tolerance and consequent tissue damage, which can be local or systemic. Given their high prevalence, close to 5% of the population, their chronic and incurable nature, and their significant morbidity and mortality, these diseases have an adverse impact both on the quality of life of those who suffer from them and on the use of health resources. The IADs differ phenotypically and have different diagnostic criteria, but the mechanisms that give rise to them are shared. This common origin of AIEs has been called the autoimmune tautology. However, despite the work done to date, the pathophysiology and immunogenetics of these diseases are not completely understood and many mechanisms remain to be elucidated, among which are risk and protective factors, heritability, the biological function of the incriminated genetic polymorphisms and their relationship with particular immunological and clinical characteristics (subphenotypes), epigenetic aspects, and the grouping of these diseases among themselves. The rationale for this proposal is based on the fact that families with several members affected by AIDs have multiple risk genes and that these members share common molecular mechanisms leading to AIDs. By focusing in particular on the phenotypes and subphenotypes of these families it will be possible, in a more efficient way, to identify common autoimmune genes and study their regulation as well as their association with subphenotypes. The proposal is supported by a unique cohort of families with autoimmunity that has been established at the Center for the Study of Autoimmune Diseases (CREA) of the Universidad del Rosario, in Bogota, Colombia. This will then be an association study based on highly informative families characterized by presenting familial autoimmunity, i.e. several members affected with different AIDs and at the same time with some member with polyautoimmunity, i.e. two or more well characterized AIDs in the same patient. This work will have an important impact on translational medicine and will strengthen the research capacity of CREA and the Universidad del Rosario. It will also facilitate the training of human resources and the edition of a book on Autoimmunity, as well as the academic integration with graduate and undergraduate students. Its results will be widely disseminated nationally and internationally, and will be the subject of several scientific publications.