Human plasma-derived mannose-binding lectin: a phase I safety and pharmacokinetic study

2.50
Hdl Handle:
http://hdl.handle.net/2336/14486
Title:
Human plasma-derived mannose-binding lectin: a phase I safety and pharmacokinetic study
Authors:
Valdimarsson, H; Vikingsdottir, T; Bang, P; Saevarsdottir, S; Gudjonsson, J E; Oskarsson, O; Christiansen, M; Blou, L; Laursen, I; Koch, C
Citation:
Scand. J. Immunol. 2004, 59(1):97-102
Issue Date:
1-Jan-2004
Abstract:
Mannose-binding lectin (MBL) is an important component of innate immunity that can bind to certain sugar residues on the surface of many types of pathogenic micro-organisms. On binding, MBL generates opsonic activity mainly through activation of the complement system. Genetically determined MBL deficiency is very common and can be associated with increased susceptibility to a variety of infections, especially in children and immunosuppressed individuals. The potential benefits of MBL reconstitution therapy therefore need to be evaluated. We have carried out a phase I safety and pharmacokinetic study on 20 MBL-deficient healthy adult volunteers. The MBL was prepared from plasma of nonremunerated, voluntary Danish donors tested and found negative for hepatitis B surface antigen, antibodies to human immunodeficiency virus (HIV) and hepatitis C virus. Each volunteer received a total of 18 mg of MBL in three 6 mg doses given intravenously, once weekly over a period of 3 weeks. The volunteers were closely monitored at the University Hospital in Reykjavik for 8 h after each infusion and daily thereafter for 5 days after each infusion. No adverse clinical or laboratory changes were observed in any of the 20 participants, and frequent measurements did not reveal any signs of infusion-associated complement activation. No antibodies to MBL, HIV or hepatitis viruses were observed 24 weeks after the last infusion. Serum MBL levels increased up to normal levels (1200-4500 ng/ml) immediately after each infusion, but the half-life of the infused MBL was highly variable, ranging from 18 to 115 h (mean 69.6). It is concluded that infusion of purified MBL as prepared by Statens Serum Institut (SSI) is safe. However, adults have to be given at least 6 mg twice or thrice weekly for maintaining protective MBL levels assumed to be about 1000 ng/ml.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.blackwell-synergy.com/doi/abs/10.1111/j.0300-9475.2004.01357.x

Full metadata record

DC FieldValue Language
dc.contributor.authorValdimarsson, H-
dc.contributor.authorVikingsdottir, T-
dc.contributor.authorBang, P-
dc.contributor.authorSaevarsdottir, S-
dc.contributor.authorGudjonsson, J E-
dc.contributor.authorOskarsson, O-
dc.contributor.authorChristiansen, M-
dc.contributor.authorBlou, L-
dc.contributor.authorLaursen, I-
dc.contributor.authorKoch, C-
dc.date.accessioned2007-11-06T09:06:00Z-
dc.date.available2007-11-06T09:06:00Z-
dc.date.issued2004-01-01-
dc.date.submitted2007-11-06-
dc.identifier.citationScand. J. Immunol. 2004, 59(1):97-102en
dc.identifier.issn0300-9475-
dc.identifier.pmid14723627-
dc.identifier.pmid10.1111/j.0300-9475.2004.01357.x-
dc.identifier.otherAAI12-
dc.identifier.urihttp://hdl.handle.net/2336/14486-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractMannose-binding lectin (MBL) is an important component of innate immunity that can bind to certain sugar residues on the surface of many types of pathogenic micro-organisms. On binding, MBL generates opsonic activity mainly through activation of the complement system. Genetically determined MBL deficiency is very common and can be associated with increased susceptibility to a variety of infections, especially in children and immunosuppressed individuals. The potential benefits of MBL reconstitution therapy therefore need to be evaluated. We have carried out a phase I safety and pharmacokinetic study on 20 MBL-deficient healthy adult volunteers. The MBL was prepared from plasma of nonremunerated, voluntary Danish donors tested and found negative for hepatitis B surface antigen, antibodies to human immunodeficiency virus (HIV) and hepatitis C virus. Each volunteer received a total of 18 mg of MBL in three 6 mg doses given intravenously, once weekly over a period of 3 weeks. The volunteers were closely monitored at the University Hospital in Reykjavik for 8 h after each infusion and daily thereafter for 5 days after each infusion. No adverse clinical or laboratory changes were observed in any of the 20 participants, and frequent measurements did not reveal any signs of infusion-associated complement activation. No antibodies to MBL, HIV or hepatitis viruses were observed 24 weeks after the last infusion. Serum MBL levels increased up to normal levels (1200-4500 ng/ml) immediately after each infusion, but the half-life of the infused MBL was highly variable, ranging from 18 to 115 h (mean 69.6). It is concluded that infusion of purified MBL as prepared by Statens Serum Institut (SSI) is safe. However, adults have to be given at least 6 mg twice or thrice weekly for maintaining protective MBL levels assumed to be about 1000 ng/ml.en
dc.language.isoenen
dc.publisherBlackwell Scientific Publicationsen
dc.relation.urlhttp://www.blackwell-synergy.com/doi/abs/10.1111/j.0300-9475.2004.01357.xen
dc.subject.meshImmunologic Deficiency Syndromesen
dc.subject.meshMannose-Binding Lectinen
dc.titleHuman plasma-derived mannose-binding lectin: a phase I safety and pharmacokinetic studyen
dc.typeArticleen
dc.identifier.journalScandinavian journal of immunologyen
dc.format.digYES-

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