Test ID: MBL    
Mannose-Binding Lectin, Serum

Evaluation of children and adults with a clinical history of recurrent infections

Results may be useful for genetic counseling and support aggressive management of recurrent infections in patients with reduced levels of mannose-binding lectin

Mannose-binding lectin (MBL) is a member of the collectin family of proteins that are characterized structurally by the presence of collagenous regions and lectin domains in the same subunit. The subunit structure of MBL is comprised of three 32kDa peptide chains organized in a triple helix with 3 C-terminal lectin domains. Circulating (functional) MBL is comprised of oligomers of subunits (dimers through tetramers account for approximately 75% of circulating MBL) that are associated with an MBL-associated serine protease (MASP). There is a single MBL gene (4 exons) on chromosome 10 with 4 known allelic variants: wild type MBL (A), and 3 mutant forms B, C, and D caused by point mutations in 3 different codons. The mutant forms of MBL form oligomers poorly, and have diminished complement activating activity (see below). Multimeric MBL binds to many different oligosaccharide moieties, including those in the cell walls of many different bacteria, yeasts, and some viruses, including HIV 1, HIV 2, and influenza A. Binding of MBL results in complement activation by the classical pathway through activation of complement 4 (C4) by MASP, and surface bound MBL enhances phagocytosis by interacting with collectin receptors on phagocytic cells. Mutations of MBL codons (homozygous or heterozygous haplotypes) are associated with diminished opsonophagocytic activity and diminished serum levels of MBL measured immunochemically (MBL deficiency). MBL-deficient individuals have increased susceptibility to infection particularly if MBL deficiency occurs concomittantly with another heritable immune system abnormality, eg, C4 null alleles or immunoglobulin class or subclass deficiencies.

> or =7.8 ng/mL

This reference range applies only to adults.

See Cautions for further information regarding the reference range and clinical interpretation.

Diminished levels of serum mannose-binding lectin (MBL) are consistent with the diagnosis of MBL deficiency.

Levels <7.8 ng/mL are associated with homozygous or mixed heterozygous mutant forms of MBL or mutations in the MBL promoter gene.

Measurement of mannose-binding lectin (MBL) immunochemically is highly dependent on the specificity of reagent anti-MBL antibody used to bind and detect MBL. Antibodies that detect multimers correlate with functional MBL activity and can be used to screen suspected individuals for functional MBL deficiency. Measured with multimer specific anti-MBL, the frequency distribution of MBL levels in sera from healthy individuals is multimodal. According to a reference range study conducted at Mayo Clinic, approximately 14% of healthy individuals may have a measurable level <100 ng/mL. Accordingly, levels <100 ng/mL should be interpreted in the clinical context of the patient. The finding of a markedly reduced level of MBL may also occur in some healthy individuals. Identification of MBL deficiency does not exclude other etiologies that predispose to increased risk of infection.

1. Pettigrew HD, Teuber SS, Gershwin ME: Clinical significance of complement deficiencies. Ann NY Acad Sci 2009;1173:108-123

2. Botto M, Kirschfind M, Maco P, et al: Complement in human diseases: lessons from complement deficiencies. Mol Immunol 2009;48:2774-2783

3. Thiel S, Frederiksen PD, Jensenius JC: Clinical manifestations of mannan-binding lectin deficiency. Mol Immunol 2006;43:86-96