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Monoclonal antibodies for the detection of desialylation of erythrocyte membranes during haemolytic disease and haemolytic uraemic syndrome caused by the in vivo action of microbial neuraminidase

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Abstract

Especially in childhood, the in vivo action of microbial neuraminidase may cause haemolytic anaemia or life-threatening haemolytic uraemic syndrome. The exposure of the Thomsen-Friedenreich (T) crypto-antigen and T-antigen polyagglutinability of erythrocytes has been described as the first sign of toxic cleavage of N-acetylneuraminic acid (Neu5Ac) from sialoglycoproteins of cell membranes. This phenomenon may, however, be too unspecific to initiate treatment for toxin elimination. The present study investigated the diagnostic effectiveness of a panel of three monoclonal antibodies (mcabs) for the estimation of the clinical significance of neuraminidase action in vivo. Depending on the amount of Neu5Ac released, the mcabs I-C4, II-Q9 and III-Y12 recognized different epitopes on erythrocyte asialoglycophorin. In 1345 patients, the mcab II-Q9 detected cleavage of Neu5Ac in 32 children who had T-antigen polyagglutinability and mild to moderate haemolytic anaemia. However, only 10 patients, whose erythrocytes were agglutinated by the mcabs III-Y12 or I-C4, developed severe haemolysis, thrombocytopenia, and finally the life-threatening haemolytic uraemic syndrome (p<0.0002). In conclusion, these mcabs provided an early marker of the in vivo action of neuraminidase. Two different degrees of erythrocyte desialylation, as defined by these mcabs, are suggested to reflect the severity of toxin-associated disease.

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References

  1. Schauer R, Shukla AK, Schröder C, Müller E (1984) The anti-recognition function of sialic acids: studies with erythrocytes and macrophages. Pure Appl Chem 56: 907-21.

    CAS  Google Scholar 

  2. Choi SI, Simone JV, Journey LJ (1972) Neuraminidase-induced thrombocytopenia in rats. Br J Haematol 22: 93-101.

    PubMed  CAS  Google Scholar 

  3. Greenberg JP, Packham MA, Guccione MA, Rand ML, Reimers HJ, Mustard JF (1979) Survival of rabbit platelets treated in vitro with chymotrypsin, plasmin, trypsin or neuraminidase. Blood 53: 916-27.

    PubMed  CAS  Google Scholar 

  4. Yee HF, Kuwata JH, Langer GA (1991) Effects of neuraminidase on cellular calcium and contraction in cultured cardiac myocytes. J Mol Cell Cardiol 23: 175-85.

    Article  PubMed  CAS  Google Scholar 

  5. Klein PJ, Bulla M, Newman RA et al. (1977) Thomsen-Friedenreich antigen in haemolytic-uraemic syndrome Lancet ii: 1024-25.

  6. Vierbuchen M, Klein PJ (1983) Histochemical demonstration of neuraminidase effects in pneumococcal meningitis. Lab Invest 48: 181-86.

    PubMed  CAS  Google Scholar 

  7. Poschmann A, Fischer K, Grundmann A, Vongjirad A (1976) Neuraminidase-induzierte hämolyse. Mschr Kinderheilk 124: 15-24.

    PubMed  CAS  Google Scholar 

  8. Novak RW, Martin CR, Orsini EN (1983) Hemolytic-uremic syndrome and T-cryptantigen exposure by neuraminidase-producing pneumococci: an emerging problem? Pediatr Pathol 1: 409-13.

    PubMed  CAS  Google Scholar 

  9. Alon U, Adler StP, Chan JCM (1984) Hemolytic-uremic syndrome associated with streptococcus pneumoniae Am J Dis Childh 138: 496-99.

    CAS  Google Scholar 

  10. Rumpf KW, Lynen R, Verwiebe R, Schilling H, Neumeyer H (1990) Hämolytisch-urämisches syndrom des Erwachsenen mit T-kryptantigen-Freilegung. Dtsch Med Wschr 115: 1270-75.

    Article  PubMed  CAS  Google Scholar 

  11. Drzeniek R (1972) Viral and bacterial neuraminidases. Curr Top Microbiol Immunol 59: 35.

    PubMed  CAS  Google Scholar 

  12. Seger RA, Kenny A, Bird GWG, Wingham J, Baals H, Stauffer UG (1981) Pediatric surgical patients with severe anaerobic infection: report of 16 T-antigen positive cases and possible hazards of blood transfusion. J Ped Surg 16: 905-10.

    Article  Google Scholar 

  13. Williams RA, Brown EF, Hurst D, Franklin LC (1989) Transfusion of infants with activation of erythrocyte T antigen. J Pediatr 115: 949-53.

    Article  PubMed  CAS  Google Scholar 

  14. Fischer K, Poschmann A, Oster H (1971) Haämolyse bei schwerer Pneumonie infolge Neuraminidasewirkung — Immun fluoreszenzdarstellung der Cryptantigene. Mschr Kinderheilk 119: 2-8.

    PubMed  CAS  Google Scholar 

  15. Placzek MM, Gorst DW (1987) T activation haemolysis and death after blood transfusion. Arch Dis Child 62: 743-44.

    PubMed  CAS  Google Scholar 

  16. Mullard GW, Thompson IH, Lee D, Owen WG (1981) Strong T-transformation associated with a severe haemolytic reaction in a young infant transfused with packed red cells. Clin Lab Haemat 3: 357-64.

    CAS  Google Scholar 

  17. Beattie KM, Lewis PE, Briske JE, Strauch BM (1985) Detection of circulating T-activating enzyme in the serum of a patient having hemolytic-uremic syndrome and disseminated intravascular coagulation. Am J Clin Pathol 84: 244-48.

    PubMed  CAS  Google Scholar 

  18. Martinot A, Hue V, Leclerc F, Chenaud M(1989) Haemolyticuraemic syndrome associated with Streptococcus pneumoniae meningitis. Eur J Pediatr 148: 648-49.

    Article  PubMed  CAS  Google Scholar 

  19. Erickson LC, Smith WS, Biswas AK, Camarca MA, Waecker NJ (1994) Streptococcus pneumoniae-induced hemolytic uremic syndrome: a case for early diagnosis. Pediatr Nephrol 8: 211-13.

    Article  PubMed  CAS  Google Scholar 

  20. Rickard KA, Robinson RJ, Worlledge SM (1969) Acute acquired haemolytic anaemia associated with polyagglutination. Arch Dis Childh 44: 102-5.

    Article  PubMed  CAS  Google Scholar 

  21. Terao T, Irimura T, Osawa T (1975) Purification and characterization of a hemagglutinin from Arachis hypogaea. Hoppe-Seyler2019;s Z Physiol Chem 356: 1685-92.

    PubMed  CAS  Google Scholar 

  22. Pereira MEA, Kabat EA, Lotan R, Sharon N (1976) Immunochemical studies on the specificity of the peanut [Arachis hypogaea] agglutinin. Carbohydr Res 51: 107-18.

    Article  PubMed  CAS  Google Scholar 

  23. Obeid D, Bird GWG, Wingham J (1977) Prolonged erythrocyte T-polyagglutination in two children with bowel disorders. J Clin Pathol 30: 953-55.

    PubMed  CAS  Google Scholar 

  24. Stähli C, Staehelin T, Miggiano V, Schmidt J, Häring P (1980) High frequencies of antigen-specific hybridomas: dependence on immunization parameters and prediction by spleen cell analysis. J Immunol Methods 32: 297-304.

    Article  PubMed  Google Scholar 

  25. Kearny JF, Radbruch A, Liesegang B, Rejewsky K (1979) A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol 123: 1548-50.

    Google Scholar 

  26. Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256: 495-97.

    Article  PubMed  Google Scholar 

  27. Fazekas de St Groth S, Scheidegger D (1980) Production of monoclonal antibodies: strategy and tactics. J Immunol Method 35: 1-21.

    Article  Google Scholar 

  28. Anstee DJ, Edwards PAW (1982) Monoclonal antibodies to human erythrocytes. Eur J Immunol 12: 228-32.

    PubMed  CAS  Google Scholar 

  29. Tenner AJ, Lesavre PH, Cooper NR (1981) Purification and radiolabeling of human Clq. J Immunol 127: 648-53.

    PubMed  CAS  Google Scholar 

  30. Höpner W, Fischer K, Jacquinet JC, Paulsen H, Poschmann A (1980) Bindung eines synthetischen 125-J-markierten T-Antigens an Seren von Mammakarcinom-Patienten. In Uhlenbruck, Wintzer (eds): CEA und andere Tumormarker. pp 320-31 Leonberg: Tumordiagnostik-Verlag

    Google Scholar 

  31. Ratcliffe RM, Baker DA, Lemieux RU (1981) Synthesis of the T (βD—Gal(1-3) αDGalNAc) antigenic determinant in a form useful for the preparation of an effective artificial antigen and the corresponding immunoadsorbent. Carbohydr Res 93: 35-41

    Article  PubMed  CAS  Google Scholar 

  32. Kornfeld R, Kornfeld S (1970) The structure of a phytohemagglutinin receptor site from human erythrocytes. J Biol Chem 245: 2536-45.

    PubMed  CAS  Google Scholar 

  33. 33 Thomas DB, Winzler RJ (1971) Structure of glycoproteins of human erythrocytes. Biochem J 124: 55-59.

    PubMed  CAS  Google Scholar 

  34. Tomita M, Furthmayr H, Marchesi VT (1978) Primary structure of human erythrocyte glycophorin A. Isolation and characterization of peptides and complete amino acid sequence. Biochemistry 17: 4756-70.

    Article  PubMed  CAS  Google Scholar 

  35. Thomas DB, Winzler RJ (1969) Structural studies on human erythrocyte glycoproteins. J Biol Chem 244: 5943-46.

    PubMed  CAS  Google Scholar 

  36. Moores P, Pudifin D, Patel PL (1975) Severe hemolytic anemia in an adult associated with anti-T. Transfusion 15: 329-33.

    Article  PubMed  CAS  Google Scholar 

  37. Kolb H, Kolb-Bachofen V (1978) A lectin-like receptor on mammalian macrophages. Biochem Biophys Res Commun 85: 678-83.

    Article  PubMed  CAS  Google Scholar 

  38. Warren R, Doyle D (1981) Turnover of the surface proteins and the receptor for serum asialoglycoproteins in primary cultures of rat hepatocytes. J Biol Chem 256: 1346-55.

    PubMed  CAS  Google Scholar 

  39. Aminoff D, Vorder Bruegge WF, Bell WC, Sarpolis K, Williams R (1977) Role of sialic acid in survival of erythrocytes in the circulation: Interaction of neuraminidase-treated and untreated erythrocytes with spleen and liver at the cellular level. Proc Natl Acad Sci USA 74: 1521-24.

    Article  PubMed  CAS  Google Scholar 

  40. Müller E, Schröder C, Schauer R, Sharon N(1983) Binding and phagocytosis of sialidase-treated rat erythrocytes by a mechanism independent of opsonins. Hoppe Seyler2019;s Z Physiol Chem 364: 1419-29.

    PubMed  Google Scholar 

  41. Stenberg PE, Levin J, Baker G, Mok Y, Corash L (1991) Neuraminidase-induced thrombocytopenia in mice: effects on thrombopoiesis. J Cell Physiol 147: 7-16.

    Article  PubMed  CAS  Google Scholar 

  42. Nordt FJ, Knox RJ, Seaman GVF (1978) Red cell aging. II. Anomalous electrophoretic properties of neuraminidase treated human erythrocytes. J Cell Physiol 97: 209-20.

    Article  PubMed  CAS  Google Scholar 

  43. Brown EJ, Joiner KA, Frank MM (1983) Interaction of desialated guinea pig erythrocytes with the classical and alternative pathways of guinea pig complement in vivo and in vitro. J Clin Invest 71: 1710-19.

    Article  PubMed  CAS  Google Scholar 

  44. Lambré CR, Kazatchkine MD, Maillet F, Thibon M (1982) Guinea pig erythrocytes, after their contact with influenza virus, acquire the ability to activate the human alternative complement pathway through virus-induced desialation of the cells. J Immunol 128: 629-34.

    Google Scholar 

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-Christiane Seitz, R., Poschmann, A. & Hellwege, H. Monoclonal antibodies for the detection of desialylation of erythrocyte membranes during haemolytic disease and haemolytic uraemic syndrome caused by the in vivo action of microbial neuraminidase. Glycoconj J 14, 699–706 (1997). https://doi.org/10.1023/A:1018565316310

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