SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION

BACKGROUND

Immune dysregulation encompasses multiple different conditions in which the immune system does not function properly and displays inappropriate or inadequate responses, overreactions or under-reactions directed towards external or internal targets. It is a broad term, and its manifestations include several different categories of disease:

Immunodeficiencies: These disorders impair the immune system's ability to defend the body against foreign or abnormal cells that invade or attack it (such as bacteria, viruses, fungi, and cancer cells). As a result, unusual bacterial, viral, or fungal infections or lymphomas or other cancers may develop. Primary immunodeficiencies (PIDs) comprise a group of nearly 500 inherited disorders, often due to single-gene mutations that result in the specific impairments in immune function. Secondary immunodeficiencies (SIDs) involve a weakened immune system caused by external sources e.g. chemical (chemotherapy), infection (HIV) or cancer.

Autoimmune Disorders: In these conditions the production of autoantibodies against self-antigens causes the immune system to attack healthy cells and tissues. Some of the most common examples include type 1 diabetes (T1D), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE).

Autoinflammatory Disorders: Here dysregulation of the innate immune system leads to spontaneous and recurrent inflammatory episodes. In contrast to autoimmune diseases where antibodies against self-antigens play a central role, the defect in autoinflammatory diseases often lies in the first responder, innate, arm of the immune system where the defect triggers inappropriate activation of the normal inflammatory response or disables resolution thereof. Examples include familial Mediterranean fever (FMF) and cryopyrin-associated periodic syndromes.