espite considerable research efforts, the aetiology of systemic lupus erythematosus (SLE) remains elusive. Genetic, hormonal and environmental factors contribute to the pathogenesis of SLE. The prominent pathogenic role of immune dysregulation is witnessed by the numerous aberrations of the immune system that have been reported in SLE (Ref. 1).
The immune system has evolved to recognize and respond to antigens (Ags) that engage specialized receptors present on the surface of T and B cells [T-cell receptors (TCRs) and B-cell receptors (BCRs), respectively]. Engagement of the TCR or BCR elicits a series of interacting intracellular biochemical events that transmit the extracellular signal (encounter of Ag) to the nucleus 2,3 . Depending on the degree and extent of integration of other membrane receptor-initiated specific accessory signals, the outcome of TCR or BCR stimulation can vary considerably. AgΓreceptor engagement can result in cell activation, proliferation, secretion of soluble mediators [cytokines or antibodies (Abs)], phenotypic changes, acquisition of effector functions, anergy and programmed cell death. Because TCR-or BCR-mediated signaling events direct these diverse but equally important outcomes, it is likely that the diverse cellular aberrations described in lupus patients reflect signaling defect(s) and that these defects are central to the pathogenesis of the disease. Such defects might derive from the abnormal expression of a signaling molecule(s) as a result of either defective gene(s) or defective regulation of gene expression.