Restoration of MBL-deficiency: redefining the safety, efficacy and viability of MBL-substitution therapy

M P Keizer; D Wouters; L J Schlapbach; T W Kuijpers

doi:10.1016/j.molimm.2014.06.005

Restoration of MBL-deficiency: redefining the safety, efficacy and viability of MBL-substitution therapy

Mol Immunol. 2014 Oct;61(2):174-84. doi: 10.1016/j.molimm.2014.06.005. Epub 2014 Jul 16.

Authors

M P Keizer¹, D Wouters², L J Schlapbach³, T W Kuijpers⁴

Affiliations

¹ Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner Laboratory of the Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatric Hematology, Immunology & Infectious Diseases, Emma Children's Hospital, AMC, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: m.keizer@sanquin.nl.
² Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner Laboratory of the Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
³ Paediatric Critical Care Research Group, Mater Research, University of Queensland, Brisbane, Australia.
⁴ Department of Pediatric Hematology, Immunology & Infectious Diseases, Emma Children's Hospital, AMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Blood Cell Research, Sanquin Blood Supply, Division Research and Landsteiner Laboratory of the AMC, University of Amsterdam, Amsterdam, The Netherlands.

PMID: 25044097
DOI: 10.1016/j.molimm.2014.06.005

Abstract

MBL-deficiency is a commonly occurring deficiency of the innate immune system, affecting a substantial part of the population and has been extensively studied. MBL appears to function as a disease modifier. The role of MBL in different conditions is context-dependent. Many clinical studies show conflicting results, which can be partially explained by different definitions of MBL-deficiency, including phenotype- and genotype-based approaches. In this review we give an overview of literature of MBL, its role in different pathologies, diseases and patient populations. We review MBL replacement studies, and discuss the potential of MBL substitution therapy. We finally suggest that new MBL substitution trials should be conducted within a predefined patient population. MBL-deficiency should be based on serum levels and confirmed by genotyping.

Keywords: Lectin pathway; MBL replacement therapy; MBL-deficiency; MBL-genotype.

Publication types

Review

MeSH terms

Genetic Predisposition to Disease
Genotype
Humans
Mannose-Binding Lectin / chemistry
Mannose-Binding Lectin / deficiency*
Mannose-Binding Lectin / genetics
Mannose-Binding Lectin / immunology
Mannose-Binding Lectin / metabolism
Mannose-Binding Lectin / therapeutic use
Mannose-Binding Protein-Associated Serine Proteases / chemistry
Mannose-Binding Protein-Associated Serine Proteases / genetics
Mannose-Binding Protein-Associated Serine Proteases / metabolism
Metabolism, Inborn Errors / therapy*
Recombinant Proteins / therapeutic use
Treatment Outcome

Substances

Mannose-Binding Lectin
Recombinant Proteins
Mannose-Binding Protein-Associated Serine Proteases

Supplementary concepts

Mannose-Binding Protein Deficiency