Recent studies by our and other groups have determined that almost all neonatal lupus infants and their mothers possess La (SSB) and/or Ro (SSA) antibodies. These data indicate that the Ro and La antibodies are of maternal origin and pass via the placenta to the infant. The clinical manifestations of the neonatal lupus syndrome are increased fetal wastage (i.e. increased incidence of abortions in the first trimester and perhaps stillbirths), isolated congenital heart block, cutaneous lupus lesions, and perhaps dyslexia. This experiment of nature constitutes the best evidence indicating a pathologic role for the Ro and La antibodies in the development of the clinical features of lupus. To study this experiment of nature further, we plan to create a mouse model by injecting mouse Ro and La monoclonal antibodies into pregnant mice to determine the effects of these antibodies upon neonatal pups. Specifically, we plan to purify Ro and La antigens, develop sensitive ELISA assays for the quantitation of Ro and La antibodies and raise monoclonal mouse Ro and La antibodies using hybridoma technology. Following the characterization of the class, specificity, and homogeneity of the monoclonal Ro and La antibody, we plan to inject these antibodies into pregnant mice during different times of the gestational period. Prior to term, the pregnant mice will be sacrificed and the uterine contents examined. The mouse fetuses will be examined histologically for evidence of inflammatory lesions in the heart, brain, and skin. Other experiments will be performed on living mouse pups from Ro and La injected mother to determine the presence of cardiac conduction abnormalities by microelectrocardiograms and the ability of UV-B exposure to induce in these mice abnormal, inflammatory cutaneous responses similar to that seen in human neonatal lupus infants.
