Reconstitution of opsonizing activity by infusion of mannan-binding lectin (MBL) to MBL-deficient humans

TY - JOUR

T1 - Reconstitution of opsonizing activity by infusion of mannan-binding lectin (MBL) to MBL-deficient humans

AU - Valdimarsson, H

AU - Stefansson, M

AU - Vikingsdottir, T

AU - Arason, G J

AU - Koch, C

AU - Thiel, S

AU - Jensenius, J C

PY - 1998/8/1

Y1 - 1998/8/1

N2 - Mannan-binding lectin (MBL, previously named mannan-binding protein, MBP) is a serum collectin, which activates complement upon binding to microbial carbohydrates. This results in opsonization of the microorganisms as well as direct complement-mediated killing. Clinical evidence indicates that MBL has an important role in the innate immune defence against various pathogens. Genetically determined MBL deficiency is associated with increased susceptibility to infections. We have infused two MBL-deficient individuals with clinical grade MBL, purified from pooled donor plasma, in doses sufficient to attain normal concentration of MBL in serum. This resulted in normalization of complement-mediated opsonization. An initial rapid decrease in the serum concentration of MBL was followed by a slower decline with an estimated half-life of about 6 days. No adverse effects were observed and anti-MBL antibodies could not be detected following several MBL infusions. One of the two MBL recipient, a two-year-old girl, who had been suffering from repeated infections from the age of 4 months, was given a total of six MBL infusions. She has subsequently remained healthy for more than three years.

AB - Mannan-binding lectin (MBL, previously named mannan-binding protein, MBP) is a serum collectin, which activates complement upon binding to microbial carbohydrates. This results in opsonization of the microorganisms as well as direct complement-mediated killing. Clinical evidence indicates that MBL has an important role in the innate immune defence against various pathogens. Genetically determined MBL deficiency is associated with increased susceptibility to infections. We have infused two MBL-deficient individuals with clinical grade MBL, purified from pooled donor plasma, in doses sufficient to attain normal concentration of MBL in serum. This resulted in normalization of complement-mediated opsonization. An initial rapid decrease in the serum concentration of MBL was followed by a slower decline with an estimated half-life of about 6 days. No adverse effects were observed and anti-MBL antibodies could not be detected following several MBL infusions. One of the two MBL recipient, a two-year-old girl, who had been suffering from repeated infections from the age of 4 months, was given a total of six MBL infusions. She has subsequently remained healthy for more than three years.

KW - Adult

KW - Carrier Proteins

KW - Child, Preschool

KW - Collectins

KW - Drug Stability

KW - Female

KW - Humans

KW - Immunologic Deficiency Syndromes

KW - Lectins

KW - Male

KW - Mannans

KW - Opsonin Proteins

M3 - Journal article

C2 - 9716101

SN - 0300-9475

VL - 48

SP - 116

EP - 123

JO - Scandinavian Journal of Immunology

JF - Scandinavian Journal of Immunology

IS - 2

ER -