29 - Autoimmune Disease

Abstract

This chapter examines several aspects of Autoimmune diseases (AID), including their discovery, clinical examples, related animal models, predisposing and triggering factors, cellular mechanisms, and conventional and immunotherapeutic treatments. AID are pathophysiological states in which the host's own tissues are damaged as a result of these immune system attacks. A large number of AID have been identified that vary widely in their effects on patients, since symptoms depend on the identity and location of self antigen under attack in each case. Examples of human AID include systemic lupus erythematosus, rheumatoid arthritis, rheumatic fever, type 1 diabetes mellitus, multiple sclerosis, Sjögren syndrome, scleroderma, myasthenia gravis, Kawasaki disease, Guillain-Barré syndrome, inflammatory bowel disease, Goodpasture's syndrome, and immunodysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome. Underlying the diversity of these diseases are common adaptive and innate immune system defects that occur alone or in concert to deregulate peripheral tolerance. Since many immune response mechanisms subject to dysregulation involve proteins encoded by polymorphic genes, an individual's genotype, particularly the identity of their HLA alleles, may predispose them to autoimmunity. Ultimately, in an individual genetically prone to autoimmunity, the regulatory balance may be tipped toward AID by various triggers such as pathogen infection, toxin exposure, sex hormones, and neuroendocrine influences. The conventional strategies applied to the treatment of AID include anti-inflammatory agents, strategies to reduce pathogen infections, and immunosuppressive drugs. The immunotherapeutic strategies applied to the treatment of AID include strategies to block the innate immune response strategies to induce tolerance, hematopoietic cell transplantation. The chapter concludes with a brief discussion of the possible relationship between AID and cancer.