title: Restoration of MBL-deficiency: redefining the safety, efficacy and viability of MBL-substitution therapy.
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.
authors.affiliation: 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.
authors.forename: M P
authors.initials: MP
authors.lastname: Keizer
authors.affiliation: Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner Laboratory of the Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Wouters
authors.affiliation: Paediatric Critical Care Research Group, Mater Research, University of Queensland, Brisbane, Australia.
authors.forename: L J
authors.initials: LJ
authors.lastname: Schlapbach
authors.affiliation: 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.
authors.forename: T W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D037601:Mannose-Binding Lectin / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D037601:Mannose-Binding Lectin; D011994:Recombinant Proteins; D050606:Mannose-Binding Protein-Associated Serine Proteases
keywords: Lectin pathway; MBL replacement therapy; MBL-deficiency; MBL-genotype