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.

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

“…RAs of DNase abzymes of patients with Hashimoto thyroiditis well correlate with different immunological and biochemical indices of this disease including a concentration of thyroid hormones, while decrease in their activity is related to decrease in thyroid gland damage and improvement of the clinical status [105]. Protease IgGs of patients with sepsis participate in the control of disseminated microvascular thrombosis and play important role in recovery from the disease [127]. Thus, various abzymes can play both a negative and positive role in the pathogenesis of SLE and other autoimmune or viral diseases.…”

Autoantibody-catalyzed Hydrolysis of Amyloid β Peptide

“…The idea of engineered and naturally occurring catalytic Abs with beneficial effects is not unprecedented. Naturally occurring catalytic IgMs are suggested to contribute in defense against human immunodeficiency virus (18), and reduced catalytic IgGs are correlated with death in patients with bacterial sepsis (52). Numerous other examples of catalytic Abs have been reported including proteolytic Abs to autoantigens (53,54), allo-and xenoantigens (55,56), and microbial antigens (15,57).…”

Factor VIII‐hydrolyzing IgG in acquired and congenital hemophilia

“…The occurrence of FVIII-hydrolyzing IgG has been reported in patients with hemophilia A [6], acquired hemophilia [7], sepsis [17] and renal transplantation [18]. FVIII-hydrolyzing IgG may thus be endowed with pathological roles; in inhibitor-positive patients with congenital hemophilia A, they inactivate therapeutic FVIII and hamper the control of hemorrhage.…”