CD3 ζ defects in systemic lupus erythematosus

The prototype autoimmune disease, systemic lupus erythematosus (SLE), has been known to be associated with deficiency of zeta chain, a component of the T-cell receptor-CD3 complex. Comprehensive analysis has shown that expression of the CD3 zeta chain is attenuated or absent in over half of SLE patients. Furthermore, aberrant transcripts of the CD3 zeta chain, including spliced variants lacking exon 7 or having a short 3'-untranslated region, have been detected in SLE T cells. Although attenuated expression of the CD3 zeta chain is also observed in cancer patients, infections and other autoimmune diseases, sustained attenuation of the CD3 zeta expression accompanied with aberrant transcripts are only observed in SLE. In this study, the authors review the unique features of CD3 zeta defects observed in SLE and discuss the molecular basis of the defects by recent findings in animal models, single-nucleotide polymorphisms and genome-wide association studies.