Protein Variant May Be Autoimmune Disease Risk Factor

A slight variation in an immune system protein called PTPN22 - the substitution of the amino acid tryptophan where most people have arginine - may cause susceptibility to autoimmune diseases, disorders in which the immune system mistakenly mounts an attack on the body’s own tissues, a new study says. (Neuromuscular diseaes that are autoimmune include myasthenia gravis, Lambert-Eaton syndrome, polymyositis and dermatomyositis.)

The altered PTPN22 protein, which results from a variation in the gene for PTPN22, appears to disrupt some of the fine tuning needed for a safe and effective immune response, according to findings in the December issue of Nature Genetics.

Torkel Vang of the Burnham Institute in La Jolla, Calif., and colleagues say the altered PTPN22 may interfere with the necessary dampening of an immune response normally performed by regulatory immune system cells, or with the normal destruction of self-reactive cells.

They suggest that a small molecule that specifically blocks PTPN22 molecules with tryptophan substituted for arginine could be developed and potentially be used as a treatment for a variety of autoimmune diseases.