Mutation Linked to Lupus

Researchers have shown that a mutation in the PTPN22 gene is associated with systemic lupus erythematosus (SLE), a complex, inflammatory autoimmune disease that affects multiple organs.

Investigators at the University of Minnesota School of Medicine (Minneapolis, USA; www.med.umn.edu) genotyped 525 Caucasian North Americans with SLE for the PTPN22 R620W polymorphism and compared the results with data generated from 1,961 Caucasian controls. They reported in the September 2004 issue of the American Journal of Human Genetics that the mutated form of PTPN22 appeared in approximately 16% of healthy Caucasians in the United States, while nearly 23% of lupus patients carry it.

Following activation of T cells, phosphorylation of tyrosine residues occurs through a complex signaling process involving protein tyrosine kinases, phosphatases, and a variety of adapter molecules. The non-receptor type 22 protein tyrosine phosphatase (PTPN22) is an enzyme which associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T cell receptor signaling pathway. PTPN22 contains three SH3 domains and a PTB domain-binding motif, and it is primarily expressed in lymphoid tissues.

"This appears to be a very important gene for lupus,” said senior author Dr. Timothy W. Behrens, professor of medicine at the University of Minnesota School of Medicine, "and this is the first time we have identified a variant that predisposes to many different autoimmune diseases. We hope that this discovery will lead to the identification of other genes associated with lupus and other immune disorders. We also hope this information will help us identify new drugs and therapies.”





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