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

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Abstract

Monoclonal antibodies (mAb) for rapid diagnosis and detection of invasive bacteria and identification of pathogenic factors in infectious diseases 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 α2,8-linked sialic acid ofEscherichia 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 experimentalE. 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.

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References

  1. Timmis, K.N.; Boulnois, G.J.; Bitter-Suermann, D.; Cabello, F.C.: Surface components ofEscherichia coli that mediate resistance to the bactericidal activities of serum and phagocytes. Curr. Top. Microbiol. Immunol.118: 197–218 (1985).

    PubMed  CAS  Google Scholar 

  2. Joiner, K.A.; Brown, E.J.; Frank, M.M.: Complement and bacteria: chemistry and biology in host defense. Annu. Rev. Immunol.2: 461–491 (1984).

    Article  PubMed  CAS  Google Scholar 

  3. Kasper, D.L.: Bacterial capsule—old dogmas and new tricks. J. infect. Dis.153: 407–515 (1986).

    PubMed  CAS  Google Scholar 

  4. Ørskov, F.; Ørskov, I.; Sutton, A.; Schneerson, R.; Lin, W.; Egan, W.; Hoff, G.E.; Robbins, J.B.: Form variation inEscherichia coli K1: determined by O-acetylation of the capsular polysaccharide. J. exp. Med.149: 669–685 (1979).

    Article  PubMed  Google Scholar 

  5. DeVoe, I.W.: The meningococcus and mechanisms of pathogenicity. Microbiol. Rev.46: 162–190 (1982).

    PubMed  CAS  Google Scholar 

  6. Robbins, J.B.; McCracken, G.H., Jr.; Gotschlich, E.C.; Ørskov, F.; Ørskov, I.; Hanson, L.A.;Escherichia coli K1 capsular polysaccharide associated with neonatal meningitis. New Engl. J. Med.301: 1216–1220 (1974).

    Google Scholar 

  7. Cross, A.S.; Gemski, P.; Sadoff, J.C.; Ørskov, F.; Ørskov, I.: The importance of the K1 capsule in invasive infections caused byEscherichia coli J. infect. Dis.149: 184–193 (1984).

    PubMed  CAS  Google Scholar 

  8. Kasper, D.L.; Winkelhake, J.L.; Zollinger, W.D.; Brandt, B.L.; Artenstein, M.S.: Immunochemical similarity between polysaccharide antigens ofEscherichia coli 07:K1(L): NM and group BNeisseria meningitis. J. Immun.110: 262–268 (1973).

    PubMed  CAS  Google Scholar 

  9. Jennings, H.J.; Katzenellenbogen, E.; Lugowski, C.; Michon, F.; Roy, R.; Kasper, D.L.: Structure, conformation and immunology of sialic acid-containing polysaccharides of human pathogenic bacteria. Pure appl. Chem.56: 893–905 (1984).

    Article  CAS  Google Scholar 

  10. Kazatchkine, M.D.; Nydegger, U.E.: The human alternative complement pathway: biology and immunopathology of activation and regulation. Prog. Allergy, vol. 30, pp. 193–234 (Karger, Basel 1982).

    Google Scholar 

  11. Gemski, P.; Cross, A.S.; Sadoff, J.C.: K1 antigen-associated resistance to the bactericidal activity of serum. FEMS Microbiol. Lett.9: 193–197 (1980).

    Article  Google Scholar 

  12. Artenstein, M.S.; Brandt, B.L.; Tramont, E.C.; Branche, W.C., Jr.; Fleet, H.D.; Cohen, R.L.: Serologic studies of meningococcal infection and polysaccharide vaccination. J. infect. Dis.124: 277–288 (1971).

    PubMed  CAS  Google Scholar 

  13. Cross, A.S.; Zollinger, W.; Mandress, R.; Gemski, P.; Sadoff, J.: Evaluation of immunotherapeutic approaches for the potential treatment of infections caused by K1-positiveEscherichia coli. J. infect. Dis.147: 68–76 (1983).

    PubMed  CAS  Google Scholar 

  14. Sarff, L.D.; McCracken, G.H.; Schiffer, M.S.; Glode, M.P.; Robbins, J.P.; Ørskov, I.; Ørskov, F.: Epidemiology ofEscherichia coli K1 in healthy and diseased newborns. Lanceti: 1099–1102 (1975).

    Article  Google Scholar 

  15. Söderström, T.; Stein, K.; Brinton, C.C., Jr.; Hosea, S.; Burch, C.; Hansson, H.A.; Karpa, A.; Schneerson, R.; Sutton, A.; Vann, W.I.; Hanson, L.A.: Serological and functional properties of monoclonal antibodies toEscherichia coli type I pilus and capsular antigens. Prog. Allergy, vol. 33, pp. 259–274 (Karger, Basel 1983).

    Google Scholar 

  16. Moreno, C.; Hewitt, J.; Hastings, K.; Brown, D.: Immunological properties of monoclonal antibodies specific for meningococcal polysaccharides: the protective capacity of IgM antibodies specific for polysaccharide group B. J. gen. Microbiol.129: 2451–2456 (1983).

    PubMed  CAS  Google Scholar 

  17. Kabat, E.A.; Nickerson, K.N.; Liao, J.; Grossbard, L.; Osserman, E.F.; Glickman, E.; Chess, L.; Robbins, J.B.; Schneerson, R.; Yang, Y.: A human monoclonal macroglobulin with specificity for a(2–8)-linked poly-N-acetylneuraminic acid, the capsular polysaccharide of group B meningococci andEscherichia coli K1, which crossreacts with polynucleotides and with denaturated DNA. J. exp. Med.164: 642–654 (1986).

    Article  PubMed  CAS  Google Scholar 

  18. Finne, J.: Occurrence of unique polysialosyl carbohydrate units in glycoproteins of developing brain. J. biol. Chem.257: 11966–11970 (1982).

    PubMed  CAS  Google Scholar 

  19. Finne, J.; Finne, U.; Deagostini-Bazin, H.; Goridis, C.: Occurrence of α2–8-linked polysialosyl units in neural cell adhesion molecule. Biochem. biophys. Res. Commun.112: 482–487 (1983).

    Article  PubMed  CAS  Google Scholar 

  20. Stefansson, K.; Dieperink, M.E.; Richman, D.P.; Gomez, C.M.; Marton, L.S.: Sharing of antigenic determinants between the nicotinic acetylcholine receptor and proteins inEscherichia coli Proteus vulgaris, andKlebsiella pneumoniae. New Engl. J. Med.312: 221–225 (1985).

    PubMed  CAS  Google Scholar 

  21. Keat, A.: Is spondylitis caused byKlebsiella? Immunol. Today7: 144–148 (1986).

    Article  Google Scholar 

  22. Cunningham, M.W.; Krisher, K.; Graves, D.C.; Murine monoclonal antibodies reactive with human heart and group B streptococcal membrane antigens. Infect. Immunity46: 34–41 (1984).

    CAS  Google Scholar 

  23. Dale, J.B.; Beachey, E.H.: Epitopes of streptococcal M proteins shared with cardiac myosin. J. exp. Med.162: 583–591 (1985).

    Article  PubMed  CAS  Google Scholar 

  24. Frosch, M.; Görgen, I.; Boulnois, G.J.; Timmis, K.N.; Bitter-Suermann, D.: NZB mouse system for production of monoclonal antibodies to weak bacterial antigens: isolation of an IgG antibody to the polysaccharide capsules ofEscherichia coli K1 and group B meningococci. Proc. natn. Acad. Sci. USA82: 1194–1198 (1985).

    Article  CAS  Google Scholar 

  25. Bitter-Suermann, D.; Görgen, I.; Frosch, M.: Monoclonal antibodies to weak immunogenicEscherichia coli and meningococcal capsular polysaccharides; in Normark, Protein-carbohydrate interactions in biological systems, pp. 395–396 (Academic Press, London 1986).

    Google Scholar 

  26. Frosch, M.; Peuckert, W.; Bitter-Suermann, D.: Diagnostic use of monoclonal IgG antibody to meningococcal B polysaccharide in cerebrospinal fluid. J. Microbiol.52: 253–254 (1986).

    Google Scholar 

  27. Frosch, M.; Roberts, I.; Görgen, I.; Metzger, S.; Boulnois, G.J.; Bitter-Suermann, D.: Serotyping and genotyping of encapsulatedEscherichia coli K1 sepsis isolated with a monoclonal IgG anti K1 antibody and K1 gene probes. Microbial Pathogenesis2: 319–326 (1987).

    Article  PubMed  CAS  Google Scholar 

  28. Baum, H.P.; Geissler, M.; Bitter-Suermann, D.: Improvement of preservation procedures for electron microscopic studies of bacterial polysialic acid capsules. (submitted).

  29. Saukkonen, K.; Haltia, M.; Frosch, M.; Bitter-Suermann, D.; Leinonen, M.: Antibodies to the capsular polysaccharide ofNeisseria meningitidis group B orE. coli K1 to the brains of infant rats in vitro but not in vivo. Microbial Pathogenesis1: 101–105 (1986).

    Article  PubMed  CAS  Google Scholar 

  30. Edelman, G.M.: Cell adhesion and the molecular processes of morphogenesis. A. Rev. Biochem.54: 135–169 (1985).

    Article  CAS  Google Scholar 

  31. Rutishauser, U.; Hoffman, S.; Edelman, G.M.: Binding properties of a cell adhesion molecule from neural tissue. Proc. natn. Acad. Sci. USA79: 685–689 (1982).

    Article  CAS  Google Scholar 

  32. Rutishauser, U.: Developmental biology of a neural cell adhesion molecule. Nature, Lond.310: 549–554 (1984).

    Article  CAS  Google Scholar 

  33. Murray, B.A.; Owens, G.C.; Prediger, E.A.; Crossin, K.L.; Cunningham, B.A.; Edelman, G.M.: Cell surface modulation of the neural cell adhesion molecule resulting from alternative nRNA splicing in a tissue-specific developmental sequence. J. Cell Biol.103: 1431–1439 (1986).

    Article  PubMed  CAS  Google Scholar 

  34. Rutishauser, U.; Watanabe, M.; Silver, J.; Troy, F.A.; Vimr, E.R.: Specific alteration of NCAM-mediated cell adhesion by an endoneuraminidase. J. Cell Biol.101: 1842–1849 (1985).

    Article  PubMed  CAS  Google Scholar 

  35. Sadoul, R.; Hirn, M.; Deagostini-Bazin, G.; Rougon, G.; Goridis, C.: Adult and embryonic mouse neural cell adhesion molecules have different binding properties. Nature, Lond.304: 347–349 (1983).

    Article  CAS  Google Scholar 

  36. Cunningham, B.A.: Structures of cell adhesion molecules; in Edelman, Thiery, The cell in contact. Adhesions and junctions as morphogenetic determinants, pp. 197–217 (Wiley, New York 1985).

    Google Scholar 

  37. Roth, J.; Taatjes, D.J.; Bitter-Suermann, D.; Finne, J.: Polysialic acid units are spatially and temporally expressed in developing postnatal rat kidney. Proc. natn. Acad. Sci. USA84: 1969–1973 (1987).

    Article  CAS  Google Scholar 

  38. Finne, J.; Mäkelä, P.H.: Cleavage of the polysialosyl units of brain glycoproteins by a bacteriophage endosialidase. Involvement of a long oligosaccharide segment in molecular interactions of polysialic acid. J. biol. Chem.260: 1265–1270 (1985).

    PubMed  CAS  Google Scholar 

  39. Rutishauser, U.; Thiery, J.-P.; Brackenbury, R.; Sela, B.-A.; Edelman, G.M.: Mechanisms of adhesion among cells from tissues of the chick embryo. Proc. natn. Acad. Sci. USA73: 577–581 (1976).

    Article  CAS  Google Scholar 

  40. Thiery, J.-P.; Duband, J.-L.; Rutishauser, U.; Edelman, G.M.: Cell adhesion molecules in early chicken embryogenesis. Proc. natn. Acad. Sci. USA79: 6737–6741 (1982).

    Article  CAS  Google Scholar 

  41. Roth, J.; Taatjes, D.J.; Goridis, C.; Bitter-Suermann, D.: Distribution of long chain polysialic acid of the neural cell adhesion molecule in embryonic human kidney (submitted).

  42. Roth, J.; Bendayan, M.; Orci, L.: Ultrastructural localization of intracellular antigens by the use of protein A-gold complex. J. Histochem. Cytochem.26: 1074–1081 (1978).

    PubMed  CAS  Google Scholar 

  43. Manigley, C.; Roth, J.: Applications of immunocolloids in light microscopy. IV. Use of photochemical silver staining in a simple and efficient double-staining technique. J. Histochem. Cytochem.33: 1247–1253 (1985).

    PubMed  CAS  Google Scholar 

  44. Roth, J.; Taatjes, D.J.; Heitz, P.U.; Goridis, C.; Bitter-Suermann, D.: Reexpression of long chain polysialic acid of the neural cell adhesion molecule in the malignant kidney tumor nephroblastoma (submitted).

  45. Nicolson, G.L.; Giotta, G.; Lotan, R.; Neri, A.; Poste, G.: Modifications in transformed and malignant tumor cells; in Brinkley, Porter, Int. Cell. Biol. 1976–1977, pp. 138–148 (Rockefeller University Press, New York (1977).

    Google Scholar 

  46. Burger, M.M.: Cell surface and neoplasia; in Brinkley, Porter, Int. Cell. Biol. 1976–1977, pp. 131–137 (Rockefeller University Press, New York 1977).

    Google Scholar 

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Bitter-Suermann, D., Roth, J. Monoclonal antibodies to polysialic acid reveal epitope sharing between invasive pathogenic bacteria, differentiating cells and tumor cells. Immunol Res 6, 225–237 (1987). https://doi.org/10.1007/BF02935517

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