Mannose-Binding Lectin / MBL Pathway Deficiency

Mannose-Binding Lectin / MBL Pathway Deficiency (Proteins | Antibodies | Genes | ELISA Kits)

Mannose-Binding Lectin / MBL Pathway Deficiency Background

Mannose-binding lectin (MBL), also called mannose-binding protein (MBP), is structurally similar to C1q. It binds multiple bacterial monosaccharides (mannose, N-acetylglucosamine, N-acetylmannosamine, and L-fucose) and activates associated serine proteases (MASP-2, MASP-1), which in turn activate the classical pathway. MBL deficiency is inherited in an autosomal co-dominant manner, with heterozygotes having about 10% of the normal functional level of MBL and homozygotes having less than 1% functional levels of MBL. Mannose-binding lectin / MBL deficiency has been reported in 2-7% of the British population.

Children with low levels of MBL are at increased risk of infection, especially after the loss of passive immunity (acquired from maternal IgG) but before the formation of protective antibody (around 6 months of age). Pediatric MBL-deficient individuals are especially at increased risk for meningococcal disease. Adult MBL deficiency has been associated with susceptibility to many bacterial infections but particularly encapsulated bacteria. MBL deficiency has also been associated with an increased susceptibility and clinical severity of fungal, protozoal, and viral infections as well as community-acquired pneumonia and Neisseria meningitis.

It has been proposed that dysfunction of the MBL pathway, like dysfunction of the classical pathway, also leads to autoimmune diseases. MBL deficiency has been associated with systemic lupus erythematosus / SLE across several ethnic backgrounds, and in one study SLE was increased twofold. MBL deficiency in cystic fibrosis patients leads to earlier Pseudomonas infection, an increased rate of decline in lung function, and earlier death from end-stage lung disease. In common variable immunodeficiency patients (CVID) with MBL deficiency, there is an increase in bronchiectasis, pulmonary fibrosis, and respiratory insufficiency.

Mannose-Binding Lectin / MBL Pathway Deficiency References

1. Pettigrew H D, et al. (2009). Clinical significance of complement deficiencies. Annals of the New York Academy of Sciences, 1173(1), 108-123.
2. Skattum L, et al. (2010). Complement: deficiency diseases. eLS.
3. Morgan B P, et al. (1991). Complement deficiency and disease. Immunology today, 12(9), 301-306.
4. Botto M. (1999). C1q knock-out mice for the study of complement deficiency in autoimmune disease. Experimental and clinical immunogenetics, 15(4), 231-234.
5. Sjöholm A G, et al. (2006). Complement deficiency and disease: an update. Molecular immunology, 43(1), 78-85.

Complement System
Complement System Overview
Complement System Component / Protein Regulator and Receptor
Complement Genetic Feature
Complement Activation Pathways
Complement System Role
Complement System and Diseases
Complement System Deficiency Diseases
Classical Pathway Deficiency+
- C1q Deficiency of Classical Pathway
- C2 Deficiency of Classical Pathway
- C3 Deficiency of Classical Pathway
- C1 Inhibitor/C1-INH Deficiency of Classical Pathway
Alternative Pathway Deficiency+
- Properdin Deficiency of Alternative Pathway
- Factor D Deficiency of Alternative Pathway
- Factor B Deficiency of Alternative Pathway
Complement Receptor Deficiency
Mannose-Binding Lectin / MBL Pathway Deficiency
Membrane Attack Complex/MAC Deficiency
Total Complement Activity / CH50 / CH100
Complement System Structure
Complement System Effector Functions
Anti-Complement Antibody Products