Platelet activation induced by human antibodies to interleukin-8.
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 immunoglobulin G (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-IL-8 IgG and involved FcgammaRIIa. In the 2 patients who could be followed up, antibodies were no longer detectable 4 months after heparin withdrawal. One additional patient with paraneoplastic recurrent thrombosis 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.
Regnault
Veronique
V
Hématologie, Faculté de Médecine, Nancy, France.
de Maistre
Emmanuel
E
Carteaux
Jean-Pierre
JP
Gruel
Yves
Y
Nguyen
Philippe
P
Tardy
Brigitte
B
Lecompte
Thomas
T
D000906:Antibodies / Q000097:blood / Q000494:pharmacology*; D015703:Antigens, CD / Q000502:physiology; D006493:Heparin / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007075:Immunoglobulin M / Q000494:pharmacology; D016209:Interleukin-8 / Q000276:immunology* / Q000502:physiology*; D015539:Platelet Activation / Q000187:drug effects*; D010978:Platelet Factor 4 / Q000276:immunology; D017452:Receptors, IgG / Q000502:physiology; D013921:Thrombocytopenia / Q000139:chemically induced / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016209:Interleukin-8; D017452:Receptors, IgG; D010978:Platelet Factor 4; D006493:Heparin