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Mannose-binding lectin: biology and clinical implications

Authors

  • D. L. Worthley,

    1. 1 Department of Gastroenterology, Flinders Medical Centre, 2 Division of Haematology, Royal Adelaide Hospital and Institute of Medical and Veterinary Science and 3Research and Development, Australian Red Cross Blood Service SA, Adelaide, South Australia, Australia
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  • 1 P. G. Bardy,

    1. 1 Department of Gastroenterology, Flinders Medical Centre, 2 Division of Haematology, Royal Adelaide Hospital and Institute of Medical and Veterinary Science and 3Research and Development, Australian Red Cross Blood Service SA, Adelaide, South Australia, Australia
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  • and 2,3 C. G. Mullighan 2,3

    1. 1 Department of Gastroenterology, Flinders Medical Centre, 2 Division of Haematology, Royal Adelaide Hospital and Institute of Medical and Veterinary Science and 3Research and Development, Australian Red Cross Blood Service SA, Adelaide, South Australia, Australia
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    • Present address: St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.


  • Funding: Work described in this review was funded by the Cooperative Research Consortium for Vaccine Technology (CRC-VT).

    Potential conflicts of interest: P. G. Bardy and C. G. Mullighan are members of the CRC-VT, which is examining the potential development of mannose-binding lectin as a therapeutic agent.

Correspondence to: Dr Charles Mullighan, Pathology, Mail Stop 342, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN, 38105, US. Email: charles.mullighan@stjude.org

Abstract

Abstract

The innate host defence molecule mannose-binding lectin (MBL) has attracted great interest as a potential candidate for passive immunotherapy to prevent infection. MBL is a multimeric lectin that recognizes a wide array of pathogens independently of specific antibody, and initiates the lectin pathway of complement activation. The basic structural unit is a triple helix of MBL peptides, which aggregate into complement-fixing higher-order structures (tetramers, pentamers and hexamers). The gene encoding MBL, MBL2, contains several common polymorphisms that influence transcription and assembly of the molecule into multimers. MBL2 coding alleles associated with low blood levels are present in up to 40% of Caucasoids, with up to 8% having genotypes associated with profound reduction in circulating MBL levels. Low-producing MBL2 variants and low MBL levels are associated with increased susceptibility to and severity of a variety of infective illnesses, particularly when immunity is already compromised – for example, in infants and young children, patients with cystic fibrosis, and after chemotherapy and transplantation. These observations suggest that administration of recombinant or purified MBL may be of benefit in clinical settings where MBL deficiency is associated with a high burden of infection. This review provides a background to MBL biology and disease associations, and identifies the exciting therapeutic possibilities of MBL replacement. (Intern Med J 2005; 35: 548–555)

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