High levels of catalytic antibodies correlate with favorable outcome in sepsis.
Sepsis is the leading cause of death in intensive care units and results from a deleterious systemic host response to infection. Although initially perceived as potentially deleterious, catalytic antibodies have been proposed to participate in removal of metabolic wastes and protection against infection. Here we show that the presence in plasma of IgG endowed with serine protease-like hydrolytic activity strongly correlates with survival from sepsis. Variances of catalytic rates of IgG were greater in the case of patients with severe sepsis than healthy donors (P < 0.001), indicating that sepsis is associated with alterations in plasma levels of hydrolytic IgG. The catalytic rates of IgG from patients who survived were significantly greater than those of IgG from deceased patients (P < 0.05). The cumulative rate of survival was higher among patients exhibiting high rates of IgG-mediated hydrolysis as compared with patients with low hydrolytic rates (P < 0.05). An inverse correlation was also observed between the markers of severity of disseminated intravascular coagulation and rates of hydrolysis of patients' IgG. Furthermore, IgG from three surviving patients hydrolyzed factor VIII, one of which also hydrolyzed factor IX, suggesting that, in some patients, catalytic IgG may participate in the control of disseminated microvascular thrombosis. Our observations provide the first evidence that hydrolytic antibodies might play a role in recovery from a disease.
Lacroix-Desmazes
Sébastien
S
Institut National de la Santé et de la Recherche Médicale, Unite 681, Université Paris VI, Institut des Cordeliers, 15 Rue de l'Ecole de Médecine, 75006 Paris, France. sebastien.lacroix-desmazes@u430.bhdc.jussieu.fr
Bayry
Jagadeesh
J
Kaveri
Srini V
SV
Hayon-Sonsino
David
D
Thorenoor
Nithyananda
N
Charpentier
Julien
J
Luyt
Charles-Edouard
CE
Mira
Jean-Paul
JP
Nagaraja
Valakunja
V
Kazatchkine
Michel D
MD
Dhainaut
Jean-François
JF
Mallet
Vincent O
VO
D017151:Antibodies, Catalytic / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D004211:Disseminated Intravascular Coagulation / Q000276:immunology; D005164:Factor IX / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D010949:Plasma / Q000276:immunology; D011379:Prognosis; D018805:Sepsis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D017151:Antibodies, Catalytic; D015415:Biomarkers; D005169:Factor VIII; D005164:Factor IX
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