Lupus in the Fas Lane?

Fas is a 43 kDa glycoprotein molecule which is involved in inducing apoptosis in both B and T lymphocytes. In the murine MRL/lpr-lpr model of systemic lupus erythematosus (SLE), the lymphoproliferation (lpr) mutation results in defective transcription of the gene that codes for the Fas protein. MRL mice which carry the homozygous recessive lpr mutation develop a severe early-onset genetically predetermined autoimmune syndrome characterised by high IgG and autoantibody levels and a diffuse proliferative immune complex-mediated glomerulonephritis. Interest in the importance of Fas in SLE has risen with the observation that 60% of human subjects with lupus have elevated levels of the soluble Fas receptor in their serum and that the abnormal presence of this molecule may protect lymphocytes from undergoing apoptosis. In this review the importance of Fas in autoimmune pathogenesis is discussed.