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.
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-09 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.
Seitz
R C
RC
Department of Pediatrics, University-Hospital, Hamburg, Germany.
Poschmann
A
A
Hellwege
H H
HH
D000743:Anemia, Hemolytic / Q000097:blood* / Q000201:enzymology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001666:Binding Sites, Antibody; D002241:Carbohydrates / Q000276:immunology; D004910:Erythrocyte Membrane / Q000276:immunology* / Q000378:metabolism; D006020:Glycopeptides / Q000276:immunology; D006241:Haptens / Q000276:immunology; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000201:enzymology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014734:Vibrio cholerae / Q000201:enzymology
D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D006020:Glycopeptides; D006241:Haptens; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid