Human plasma-derived mannose-binding lectin: a phase I safety and pharmacokinetic study.
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.
Valdimarsson
H
H
Department of Immunology, National University Hospital, Landspitali, University of Iceland, Reykjavik, Iceland. helgiv@landspitali.is
Vikingsdottir
T
T
Bang
P
P
Saevarsdottir
S
S
Gudjonsson
J E
JE
Oskarsson
O
O
Christiansen
M
M
Blou
L
L
Laursen
I
I
Koch
C
C
D000293:Adolescent; D000328:Adult; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000628:therapy*; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency / Q000494:pharmacology*; D008875:Middle Aged
D037601:Mannose-Binding Lectin