Anti-protein S antibodies following a varicella infection: detection, characterization and influence on thrombin generation.
Postinfectious purpura fulminans is a rare disease. Varicella is one of the precipitating conditions and we recently observed such a case. The 4-year-old child was found to have a severe transient protein S deficiency. By enzyme-linked immunosorbent assay and surface plasmon resonance we first demonstrated that anti-protein S antibodies were present and also transient. Next we characterized the epitopes against which these antibodies were directed and found that they predominantly recognized the N-terminal part of protein S. Finally we showed by thrombography a transient dramatic hypercoagulable state as a result of thrombin being unregulated by the dynamic protein C inhibitory system: in vitro thrombin generation, in response to a low concentration of tissue factor, was almost insensitive to activated protein C up to 25 nmol L(-1) on day 4 while it was normally sensitive on day 42. For the first time, we demonstrated a temporal relationship between protein S deficiency, antibodies to protein S and hypercoagulability, thus supporting the pathogenic role of these antibodies.
Regnault
V
V
Inserm 734 and Hospital of Nancy, France.
Boehlen
F
F
Ozsahin
H
H
Wahl
D
D
de Groot
P G
PG
Lecompte
T
T
de Moerloose
P
P
D001323:Autoantibodies / Q000097:blood*; D002644:Chickenpox / Q000097:blood / Q000150:complications*; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D006801:Humans; D011695:IgA Vasculitis / Q000209:etiology / Q000821:virology; D008297:Male; D017293:Protein S / Q000276:immunology*; D018455:Protein S Deficiency / Q000209:etiology / Q000821:virology; D020349:Surface Plasmon Resonance; D013917:Thrombin / Q000096:biosynthesis*; D019851:Thrombophilia / Q000209:etiology / Q000821:virology; D013997:Time Factors
D001323:Autoantibodies; D017293:Protein S; D013917:Thrombin