title: High levels of catalytic antibodies correlate with favorable outcome in sepsis.
abstract: 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.
authors.affiliation: 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
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: David
authors.initials: D
authors.lastname: Hayon-Sonsino
authors.forename: Nithyananda
authors.initials: N
authors.lastname: Thorenoor
authors.forename: Julien
authors.initials: J
authors.lastname: Charpentier
authors.forename: Charles-Edouard
authors.initials: CE
authors.lastname: Luyt
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
authors.forename: Valakunja
authors.initials: V
authors.lastname: Nagaraja
authors.forename: Michel D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dhainaut
authors.forename: Vincent O
authors.initials: VO
authors.lastname: Mallet
mesh_terms: 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
chemical_list: D017151:Antibodies, Catalytic; D015415:Biomarkers; D005169:Factor VIII; D005164:Factor IX
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