Grant: Project Grant

In many diseases, our own body produces antibodies directed against our own tissues and organs. This phenomenon of autoantibody production is called autoimmunity, which is responsible for diseases like rheumatoid arthritis and lupus. Autoimmunity is not well understood for a chronic lung disease like asthma. Eosinophils, a type of white blood cell, are a characteristic feature in asthma. Most difficult-to-control eosinophilic asthma patients are treated with a drug called prednisone (glucocorticosteroid) to control the underlying inflammation and prevent symptoms and attacks. Prednisone has severe side-effects and undesired by most patients. Even then, for reasons not yet known, the clinical symptoms of some patients remain uncontrolled, causing frequent 'flare-ups' that require immediate medical attention and hospitalization. Eosinophils produce a protein called eosinophil peroxidase which can cause damage to surrounding lung tissue. In other diseases where certain peroxidase levels are increased such as thyroid peroxidase (autoimmune thyroiditis) and myeloperoxidase (Granulomatosis with polyangitis), autoantibodies are detected against the peroxidase itself, that lead to disease. In fact, we have recently found evidence of autoantibodies against eosinophil peroxidase, in the sputum of patients with severe form of eosinophilic asthma requiring high dose corticosteroid treatment and susceptible to recurrent lung infections. We propose that asthma, in some patients, may also be an autoimmune disease. We need to better understand why and how these autoantibodies develop and how they make the disease worse. We also hope to find the connection between infections and generation of autoantibodies. Hopefully, investigating these questions will help us identify patients at risk of developing this autoimmune type of asthma, find ways of managing them with current available therapeutics or finding avenues to develop new.