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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-02-0620.
Submitted February 26, 2002
Accepted September 27, 2002
Platelet activation induced by human antibodies to interleukin-8
Veronique Regnault, Emmanuel de Maistre, Jean-Pierre Carteaux, Yves Gruel, Philippe Nguyen, Brigitte Tardy, and Thomas Lecompte*
Hematologie - Faculte de Medecine, EA 3452, Vandoeuvre-les-Nancy, France
Service d'Hematologie Biologique, CHU, Nancy, France
Clinique de Chirurgie Cardio-vasculaire, CHU, Nancy, France
Service d'Hematologie-Hemostase, CHU A. Trousseau, Tours, France
Faculte de Medecine, EA 2070, Reims, France
Hematologie, CHU, Saint-Etienne, France
* Corresponding author; email: thomas.lecompte{at}chu-nancy.fr.
Some cases of heparin-induced thrombocytopenia (HIT) have been reported to be associated with antibodies against interleukin-8 (IL-8), a chemokine related to platelet factor 4. We found that sera from 5 HIT patients containing IgG or IgM antibodies to IL-8, as evidenced using surface plasmon resonance spectroscopy, were able to trigger IL-8-dependent activation of washed platelets, leading to procoagulant activity. This activation occurred at IL-8 concentrations achievable in vivo and was facilitated by heparin (0.1 U/mL). Activation was also induced by affinity-purified anti-IL8 IgG and involved Fc RIIa. In the two patients who could be followed up, antibodies were no longer detectable 4 months after heparin withdrawal. One additional patient with paraneoplastic recurrent thromboses without thrombocytopenia was found to have platelet-activating anti-IL-8 IgM, but in this case heparin was inhibitory. This is another example of potentially pathogenic platelet activation by antibodies.
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