Monoclonal antibodies to polysialic acid reveal epitope sharing between invasive pathogenic bacteria, differentiating cells and tumor cells

Abstract

Monoclonal antibodies (mAb) for rapid diagnosis and detection of invasive bacteria and identification of pathogenic factors in infectious disease are equally important in medical microbiology and clinical pathology and may even provide a breakthrough in basic medical and cell biology research. Such a situation evolved from the application of a unique mAb against the poorly immunogenic homopolymers of alpha 2,8-linked sialic acid of Escherichia coli K1 and meningococci group B capsules which could be derived from immune-hyperreactive NZB-autoimmune mice. The cross-reactivity of this mAb with identical polysialic acid (polySA) units of the neural cell adhesion molecule (N-CAM) revealed antigenic mimicry as the basis for the escape of the above-mentioned bacteria from host immune response and immune defense. The mAb proved to be a specific and sensitive diagnostic reagent as well as a very efficient therapeutic agent in experimental E. coli K1 and meningococcal group B infections in mice. Furthermore, the mAb was found to react exclusively with long-chain polySA units characteristic of the embryonic form of N-CAM. This led to the discovery that the embryonic form of N-CAM is present outside neural tissue in the mesodermally derived kidney where it is specifically expressed during embryonic organ differentiation and reexpressed under conditions of malignant growth in nephroblastoma. Therefore, the embryonic form of N-CAM represents an onco-differentiation antigen in kidney.