The course of autoimmune disease in parous NZB/NZW mice.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that characteristically affects young women in their reproductive years (Estes and Christian, 1971 j. Many women with SLE want to have children but because a number of reports have described the adverse influence of pregnancy and parturition on the course of SLE, many clinicians advise patients with active disease to avoid childbearing. Estes and Larson (1965) reported that exacerbations of SLE during pregnancy occurred more than twice as often as remissions and concluded that active lupus nephritis was a contraindication to pregnancy. In a retrospective study of 79 patients with SLE, Fraga, Mintz, Orozco and Orozco (1974) reported the onset of disease in 11 patients during pregnancy or in the immediate postpartum period. Flares of SLE occurred in seven cases. Many studies of pregnancy in women with SLE have been criticized (Fraga, Mintz, Orozco and Orozco, 1974). Small numbers of patients were described, and in some instances articles were written by obstetricians who failed to document the diagnosis of SLE in every patient. To gain additional insight into the influence of pregnancy on SLE in women, WC studied autoimmune disease in parous and nonparous mice which are animal models of SLE. New Zealand Black (NZB) mice develop autoimmune haemolytic anaemia and membranous glomerulonephritis (Howie and Helyer, 1968). When NZB mice are crossed with New Zealand White (NZW) mice, the first-generation NZB/NZW offspring spontaneously develop a disease which is analogous to SLE. Female mice develop autoantibodies and proteinuria at an early age (5 to 6 months), and 50 per cent of virgin female mice are dead of renal failure by 10 months of age. In contrast, male mice develop renal disease 3 to 4 months later than female mice; their mean survival time is 15 months (Howie and Helyer, 1968). Positive tests for lupus erythematosus (LE) cells (Howie and Helyer, 1968), heterogeneous antinuclear antibodies detected by indirect immunofluorescence (ANA) (Lambert and Dixon, 1968) and antibodies directed specifically against DNA (anti-DNA) (Steinberg, Pincus and Talal, 1969) are found in 50 to 100 per cent of NZB/NZW mice. These serological abnormalities are characteristically associated with SLE in man (Dubois, 1974). Anti-DNA and a DNA-like antigen have been eluted from renal tissues ol sick NZB/NZW mice (Lambert and Dixon, 1968) and from kidneys of patients dying with SLE (Koffler, Schur and Kunkel, 1967). Immune complex deposition in the glomeruli, therefore, appears to cause renal disease in New Zealand mouse disease and in human SLE.