HISTOCOMPATIBILITY COMPLEX GENE-PRODUCTS AND EXPOSURE TO ESTROGEN - 2INDEPENDENT DISEASE ACCELERATING FACTORS IN MURINE LUPUS

A number of studies have demonstrated that oestrogen exerts a signific ant impact on the course of experimental autoimmune diseases. Exposure to oestrogen aggravates SLE glomerulonephritis whereas the opposite o utcome has been demonstrated in experimental arthritis, vasculitis, th yroiditis, and sialadenitis. In this report we have analysed the respe ctive impact of H-2z linked gene products and long-term treatment with physiological doses of oestradiol on clinical and immunological varia bles in castrated backcrosses of lupus prone NZB/W and NZB mice. Our r esults demonstrate that H-2z linked gene products accelerate B-cell ac tivation and stimulate autoantibody production resulting in aggravatio n of glomerulonephritis and precocious death in renal failure. These H -2z linked gene products do not influence T-cell mediated sialadenitis . Irrespectively of the H-2 haplotype of the mice, administration of o estrogen resulted in intense polyclonal B cell activation and aggravat ion of glomerulonephritis. However, exposure to oestrogen resulted in amelioration of sialadenitis. Notably, our result indicates that B-cel l activation achieved by oestrogen and H-2z gene linked products, resp ectively is mediated by independent mechanisms. In addition, we have d eveloped a predictive in vivo test that permits forecasts regarding ef ficiency of oestrogen treatment for suppression of T-cell mediated les ions. Using this test procedure in young, clinically healthy SLE mice we have been able to prove that animals displaying suppressed delayed type hypersensitivity (DTH) after short-term oestrogen exposure showed significantly lower long-term morbidity regarding development of sial adenitis upon continuous treatment with physiological doses of oestrad iol.