A platelet-activating antiglycoprotein Ib monoclonal antibody.

To the Editor: ing ones for further investigation of receptor involvement in signal transduction. However, a fully detailed characterization of all possible mechanisms of activation is necessary. In the March 1 issue, Yanabu et al reported on a platelet-activating antiglycoprotein Ib monoclonal antibody (MoAb) NNKY5-5. Hans Deckmyn The intact antibody, but not Fab-fragments, caused activation, and Karen Vanhoorelbeke (Fab*)2-fragments could not be prepared. Inhibition of the platelet Nancy Cauwenberghs FcgII-receptor by the antibody IV.3 did not prevent platelet activaLaboratory for Thrombosis Research, IRC tion by NNKY5-5. From this the investigators concluded that the KU Leuven Campus Kortrijk action of the antibody on platelets was FcgII-receptor-independent, Kortrijk, Belgium and hence due to signal transduction via glycoprotein Ib. We previously analyzed MoAb-mediated platelet activation, REFERENCES where we could show that the mechanism of activation clearly depends on the antibody subtype. Activating IgG1-antibodies can do 1. Yanabu M, Ozaki Y, Nomura S, Miyake T, Miyazaki Y, Kagawa H, Yamanaka Y, Asazuma N, Satoh K, Komiyama Y, Fukuso by cross-linking the FcgII-receptor, Fabor (Fab*)2-fragments are inactive and inhibition is obtained by blocking FcgRII. Activathara S: Tyrosine phosphorylation and p72 activation by an antiglycoprotein Ib monoclonal antibody. Blood 89:1590, 1997 ing IgG2-antibodies, on the other hand, essentially cause platelet activation via the complement system, where again Fabor (Fab*)22. De Reys S, Blom C, Lepoudre B, Declerck PJ, De Ley M, Vermylen J, Deckmyn H: Human platelet aggregation by murine fragments are inactive. However, FcgRII-inhibition has no effect but leupeptin-treatment or complement inactivation prevents platelet monoclonal antibodies is subtype-dependent. Blood 81:1792, 1993 3. Higashihara M, Maeda H, Shibata Y, Kume S, Ohashi T: A activation. High concentrations of antibody may result in cell lysis and washed platelets are not sensitive or less sensitive. monoclonal anti-human platelet antibody: A new platelet aggregating substance. Blood 65:382, 1985 In their report, Yanabu et al mention that only a minimal aggregation response to NKKY5-5 was obtained in washed platelets in con4. Stuttle AWJ, Powling MJ, Ritter JM, Hardisty RM: Effects of a monoclonal antibody to glycoprotein IIb/IIIa (P256) and of trast to what was seen in platelet-rich plasma. Furthermore, NKKY55 is an IgG2b-antibody. Both findings may be an indication that enzymically derived fragments of P256 on human platelets. Thromb Haemost 65:432, 1991 complement activation through the Fc-part of the antibody could have been involved in the platelet aggregation response. This possi5. De Reys S, Hoylaerts MF, De Ley M, Vermylen J, Deckmyn H: Fc-independent cross-linking of a novel platelet membrane probility was not really excluded. Only very few MoAbs are able to activate platelets in an Fctein by a monoclonal antibody causes platelet activation. Blood 84:547, 1994 independent manner, and they indeed represent the most interest-