Our research team works in two main investigation areas, which involve systemic autoimmune diseases (mainly Systemic Lupus Erythematosus, Primary Antiphospholipid Syndrome and Rheumatoid Arthritis) and chronic arthropaties (with special emphasis on Spondyloarthritis including Ankylosing Spondylitis and Psoriatic Arthritis). We use synergistically clinical-therapeutic, molecular and cellular approaches.
Atherothrombosis in systemic autoinmune diseases
Rheumatoid Arthritis (RA), Systemic Lupus erythematosus (SLE), and Primary Antiphospholipid Syndrome (APS), chronic multisystem autoimmune diseases with a broad range of clinical manifestations, are associated with accelerated atherosclerosis (AT) and increased risk of cardiovascular (CV) complications. Relevant factors directly influencing the development of AT in these autoimmune disorders comprise immune complex generation and changes in innate immune responses, complement activation, oxidative stress, increased production of adipokines, dysfunctional lipids, and changes in the production and activity of a complex network of cytokines. Characterization of the molecular and cellular basis of signalling abnormalities within the immune system that lead to autoreactivity and inflammation, and their relationship to early atherosclerosis and CVD development remain critical for understanding their pathogenesis.
An important aspect for the prevention and treatment of atherothrombosis is to identify at an early stage subjects with increased vascular risk, susceptible to develop thrombotic episodes. Accordingly, the identification and characterization of specific biomarkers involved in the switch of inflammatory mediators associated to CVD in each autoimmune condition is also crucial for the development of new therapeutic approaches in patients who do not respond to standard therapy or suffer resistance or relapse.
Metabolic disorders associated with systemic autoimmune and chronic inflammatory diseases
The inflammatory state associated with obesity significantly contributes to the development of diverse chronic diseases, such as autoimmune, metabolic disorders and cancer. A number of studies suggested the relevance of the reciprocal interactions between the metabolic system and the immune cells, which could explain that diseases with altered immune system may lead to metabolic disorders associated. Thus, the psoriatic and rheumatoid arthritis are chronic inflammatory diseases strongly related to diverse metabolic comorbidities such as metabolic syndrome, obesity and type II diabetes, increasing significantly the risk for cardiovascular diseases in those patients. Taking into account this strong association, it would be very important to analyze the cellular and molecular mechanisms involved and to search new biomarkers that could identify the processes leading to these comorbidities.
Inflammation and new bone formation in spondyloarthropathies
Ankylosing Spondylitis (AS) is a chronic inflammatory joint disease associated with the HLA-B27 antigen, of unknown etiology, that predominantly affects the axial skeleton, especially the sacroiliac joints. In some patients, it may be accompanied by extra-articular manifestations, such as inflammation in the eyes (UVEITIS) or in the heart valves, and the development of atherosclerosis. In the AS the distinguishing mark of bone remodeling is the pathological bone formation, which occurs in the entheses and can evolve to ankylosing, either vertebral or in peripheral joints.
Chronic inflammation and ossification in AS develop through different molecular pathways, but with probable reciprocal influence. The perpetuation of bone formation might depend to a greater or lesser extent on inflammation, but also on genetic factors, as yet unidentified and different from those that determine susceptibility to inflammatory disease. It is therefore necessary to search for new therapeutic targets and investigate the relevance of new cellular and molecular protagonists in inflammation, atherosclerosis and osteoprolifera- tion.