Past clinical and experimental observations suggest that certain skin antigens may be involved in focusing immune reactions to cutaneous sites. The major objective of the proposed studies is to examine the expression and distribution of cellular and extracellular components located in the region of the epidermal basal layer that are recognized by antibodies from serum or skin of LE patients with widespread skin disease and photosensitivity. The effect of ultraviolet light, cellular proliferation, and/or differentiation on Ro/SSA and La/SSB antigen expression will be examined using monospecific lupus and rabbit sera and monoclonal antibodies. Epidermal basement membrane zone(EBMZ) antibodies from LE patients and rabbits immunized with EBMZ material will also be used to identify and isolate the corresponding antigen. Both in vivo and in vitro systems will be used to study the distribution and expression of these antigens using immunofluorescence, immunoelectron microscopic, immunoprecipitation, gel filtration and autoradiographic techniques. Particular attention will be paid to the influence of cell cycle, cellular proliferation, differentiation and ultraviolet light on antigen expression and location. A skin organ culture system will be used to examine the mechanism(s) involved in ultraviolet light induced inflammatory mediator release and the effect of antibodies to these antigens on this process. Findings from these studies may lead to a better understanding of the mechanism(s) involved in localizing the cutaneous injury in LE to the basal layer. The findings from these studies may also provide insight into factors that are responsible for aggravating or initiating cutaneous injury in LE. This information could, in turn, lead to better methods for controlling the cutaneous injury which is such a common feature of this disorder.
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