Srinivas V . Kaveri

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Vascular endothelial cells (ECs) link hemostasis, thrombosis, and complement. ECs synthesize both the clotting initiator von Willebrand factor (VWF) and the complement regulator factor H (FH). VWF is stored in EC Weibel-Palade bodies (WPBs), but the intracellular location of FH is not well defined. We found that FH colocalizes with VWF in WPBs of human(More)
Atherosclerosis is associated with immune activation. T cells and macrophages infiltrate atherosclerotic plaques and disease progression is associated with formation of autoantibodies to oxidized lipoproteins. In the apo E knockout mouse, a genetic model of cholesterol-induced atherosclerosis, congenital deficiency of macrophages, lymphocytes, or(More)
Polyspecific antibodies represent a first line of defense against infection and regulate inflammation, properties hypothesized to rely on their ability to interact with multiple antigens. We demonstrated that IgG exposure to pro-oxidative ferrous ions or to reactive oxygen species enhances paratope flexibility and hydrophobicity, leading to expansion of the(More)
Procoagulant factor VIII (FVIII) is either produced endogenously under physiologic conditions, or administered exogenously as a therapeutic hemostatic drug in patients with hemophilia A. In the circulation, FVIII interacts with a multitude of glycoproteins, and may be used for coagulation at the sites of bleeding, eliminated by scavenger cells, or processed(More)
Central tolerance plays a key role in modulating immune responses to self and exogenous antigens. The absence of self-antigen expression, as in patients with genetic deficiencies, prevents the development of antigen-specific immune tolerance. Hence, a substantial number of patients develop neutralizing antibodies to the corresponding protein therapeutics(More)
Acquired hemophilia is a rare bleeding disorder characterized by the spontaneous occurrence of inhibitory antibodies against endogenous factor VIII (FVIII). IgG from some patients with acquired hemophilia hydrolyze FVIII. Because of the complex etiology of the disease, no clinical parameter, including the presence of FVIII-hydrolyzing IgG, has been(More)
Acquired hemophilia is a rare hemorrhagic disorder caused by the spontaneous appearance of inhibitory autoantibodies directed against endogenous coagulation factor VIII (FVIII). Inhibitory Abs also arise in patients with congenital hemophilia A as alloantibodies directed to therapeutic FVIII. Both autoimmune and alloimmune inhibitors neutralize FVIII by(More)
In the present study, we demonstrate that breast milk of 66% and 83% of HIV-seronegative and seropositive women, respectively, contains natural Abs of the secretory IgA and IgG isotypes directed against the CCR5 coreceptor for R5-tropic strains of HIV-1. Abs to CCR5 were affinity purified on a matrix to which a synthetic peptide corresponding to the second(More)
Chronic allograft nephropathy (CAN), a major cause of late allograft failure, is characterized by a progressive decline in graft function correlated with tissue destruction. Uncontrolled activation of the coagulation cascade by the stressed endothelium of the graft is thought to play an important role in the pathophysiology of CAN. In this study, we(More)
Von Willebrand factor (VWF) has been proposed to reduce the immunogenicity of therapeutic factor VIII (FVIII) in patients with hemophilia A. Using FVIII-deficient mice, we compared the immunogenicity of different preparations of plasma-derived (pd) and recombinant (r) FVIII. Treatment of mice with pdFVIII induced significantly lower titers of FVIII(More)