Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome

•Autopsy tissues from three fatal CRS cases were analyzed immunohistochemically.•Rigorous negative controls were used to verify the specificity of immunostaining.•Rubella antigen was detected in cardiac fibroblasts, alveolar macrophages, neuronal progenitor cells and endothelial cells.•Rubella antigen localization was consistent with CRS pathology.Wild type rubella virus (RV) transferred from mothers with rubella to their unborn children results in 100,000 infants/year worldwide born with birth defects collectively known as congenital rubella syndrome (CRS). Indeed, RV is the most teratogenic infectious agent known. Identifying cell types involved in RV infection of infants with CRS was possible using tissues from three Romanian infants, who unfortunately died, and using a very specific antiserum to RV. The cell types involved in RV infection which were identified were consistent with the pathology of CRS. Additional studies further enumerating the cell types involved in CRS are needed.

BackgroundAn estimated 100,000 cases of congenital rubella syndrome (CRS) occur worldwide each year. The reported mortality rate for infants with CRS is up to 33%. The cellular mechanisms responsible for the multiple congenital defects in CRS are presently unknown. Here we identify cell types positive for rubella virus (RV) in CRS infants.MethodsCells and organs involved in RV replication were identified in paraffin-embedded autopsy tissues from three fatal case-patients by histopathologic examination and immunohistochemical (IHC) staining using a rabbit polyclonal RV antibody. Normal rabbit antisera and RV antisera preabsorbed with highly purified RV served as negative controls.ResultsRV antigen was found in interstitial fibroblasts in the heart, adventitial fibroblasts of large blood vessels, alveolar macrophages, progenitor cells of the outer granular layer of the brain, and in capillary endothelium and basal plate in the placenta. The antibody specificity was verified by IHC staining of multiple tissue sections from other infectious disease cases. RV infection of each cell type is consistent with abnormalities which have been identified in patients with CRS, in the heart, large blood vessels, and brain. Antigen distribution was consistent with inflammatory response to vascular injury and systemic spread of RV.ConclusionsThe identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS.