The skin immune system: lupus erythematosus as a paradigm

Lupus erythematosus (LE) was first described as a clinical dermatological entity in 1851. The possibility of serious systemic manifestations became recognized by 1872 as the result of the work of M. Kaposi. Since then, it took a long time before LE was recognized to be an immunological disease. Recognition of antinuclear antibodies and their deposition at the basal membrane region in skin resulted in two concepts of LE pathogenesis. In one, antibody complexing and complement activation with generation of the membrane attack complex (C5–C9) is thought to be the origin of the chronic inflammatory reaction. In the other, antibody deposition enables antibody dependent cellular cytotoxity, leading to hydropic degeneration of the basal epidermal layer and subsequent chronic inflammation. Norris postulated in 1993, that the epidermis acts as a pro-inflammatory organ, in which an UVB-induced increase in cytokine production is followed by increased expression of adhesion molecules on keratinocytes as well as dermal endothelial cells. Translocation of certain antigens (i.e. Ro & La) to which circulating auto-antibodies exist in LE, enables recognition by adhesion molecule directed skin-invading T cells with subsequent cytotoxic effector activity. A persistent chronic inflammatory reaction then ensues. A similar development in knowledge may be seen in the history of immunodermatology. Originally, lupus erythematosus could not be recognized as an immune disease, since concepts of immunology were virtually non-existent when LE was first described. Immunology, in the first half of this century, was mainly antibody-oriented and thus came the concept of (S)LE as an antibody-mediated disease. Subsequently, the role of cellular immunological pathways came into focus, and cellular effector mechanisms were introduced in LE pathogenesis concepts. Ultimately, the recognition of subsystems within the (skin) immune system with cytokine networks, dermal microvascular units, and a complex interplay of both cellular and humoral immune mechanisms has resulted in a more complex but also more appreciable postulate of the pathogenesis of lupus erythematosus. The understanding of a complex immunodermatological disease is facilitated by taking into account the possible complicated interplay of subsystems within the skin immune system (SIS), with both humoral and cellular effector mechanisms.