The Genetics of Autoimmune Diseases

The fly sat upon the axle-tree of the chariot-wheel and said, "What a dust do I raise!"
Francis Bacon

About 3% to 5% of the US population is affected by an autoimmune disease, such as rheumatoid arthritis (RA), multiple sclerosis (MS), or systemic lupus erythematosus (SLE). Although it is still unclear what these diseases may have in common, they are generally grouped in the autoimmune category, as a dysregulation of the endogenous immune response (leading to damage of the patient's own tissues and organs) is thought to underlie their development and progression. RA and SLE predominantly affect the joints and the kidneys, whereas MS stems from demyelination in the central and peripheral nervous systems.

Far more women are affected than men, and heterogeneity in incidence is known to occur among different populations and different countries. MS, for example, manifests itself more frequently in young women of Northern rather than of Southern European descent. It is unclear whether such heterogeneity reflects genetic and/or environmental factors.

Cause and effect is still an elusive link in autoimmune diseases, and the therapies currently used reflect this lack of clear etiopathogenetic knowledge. All have a hereditary component, most probably polygenic in nature. Genetic regions and polymorphisms associated with each disease are being uncovered, and the most relevant were discussed at the 54th Annual Meeting of the American Society of Human Genetics, recently held in Toronto, Ontario, Canada.

Some gene associations have been confirmed, while others have been proven inconsistent or restricted to a specific population. More data will come in the near future, and they are expected to help in dissecting the genetic origin of autoimmune diseases and in unraveling their causes. In the meantime, we may want to remember that, sometimes, linkages and gene associations may just be flies sitting on a chariot wheel.