ABSTRACT
Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving several organs (1,2). The main effectors of disease pathology are the diverse autoantibodies, immune complexes and autoreactive cells. Altered biology of immune cells, keratinocytes, endothelial and possibly other cells invariably contributes to disease expression. At the pathogenic level, the disease presents unprecedented complexity, involving an as yet unspecified number of genes, immunoregulatory aberrations, environmental and hormonal factors. Previous and current research efforts have elucidated the complex array of genetic, environmental, hormonal and immunoregulatory factors thought to interplay in the disease pathogenesis. Although certain individuals may have a strong genetic predisposition to develop lupus, it is likely that more than one group of factors need to be present for disease expression. In an occasional patient, certain factors may dominate, e.g., almost all patients with C4 deficiency (3) develop lupus, suggesting that this gene represents a strong single predisposing genetic factor. Theoretically, it can be assumed that if the sum of the effects of different factors exceeds a certain threshold, then clinical manifestation of lupus ensues, while lesser sums may lead to clinical syndromes that do not fulfill the clinical diagnosis of lupus.
