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VOLUME 5 , ISSUE 1 ( Jan-Jun, 2016 ) > List of Articles

Mannose binding lectin- genetic variations, deficiency and disease associations

Farzana Begum Liakath

Keywords : Mannose binding lectin, Genetic variation, MBL deficiency, MBL therapy

Citation Information : Liakath FB. Mannose binding lectin- genetic variations, deficiency and disease associations. 2016; 5 (1):69-73.

DOI: 10.5005/jp-journals-10085-5114

License: CC BY-NC 4.0

Published Online: 01-02-2020

Copyright Statement:  Copyright © 2016; The Author(s).


Mannose-binding lectin (MBL) is an important arm of innate immunity and plays a vital role in the first line of host defense. Genetic variation in MBL2 have been shown to associate with many infectious diseases, autoimmune and inflammatory disorders such as malaria, leishmaniasis, leprosy, tuberculosis, filariasis, HIV, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). MBL has been shown to bind with glycoconjugates on the surface of mannose rich microbes and deficiency of MBL has been associated with susceptibility and modulating the severity in bacterial, fungal, protozoan and viral infections. Many different approaches are being used to define ‘MBL deficiency’. It is more relevant in young children in whom immune system fails to mount an effective response to carbohydrate antigens. MBL replacement therapy has been tried in the past for patients with MBL deficiency. Currently, production of recombinant MBL is underway and provides a hope for children with innate immune disorders.

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  1. Porter RR, Reid KB. The biochemistry of complement. Nature. 1978; 275: 699-704.
  2. Carroll MC. The complement system in regulation of adaptive immunity. Nat Immunol. 2004; 5: 981-6.
  3. Dodds AW. Which came first, the lectin/classical pathway or the alternative pathway of complement? Immunobiology. 2002; 205: 340-54.
  4. Turner MW. Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol Today. 1996; 17:532-40.
  5. Jack DL, Klein NJ, Turner MW. Mannose-binding lectin: targeting the microbial world for complement attack and opsonophagocytosis. Immunol Rev. 2001; 180:86-99.
  6. Sastry K, Herman GA, Day L, Deignan E, Bruns G, et al. The human mannose-binding protein gene. Exon structure reveals its evolutionary relationship to a human pulmonary surfactant gene and localization to chromosome 10. J Exp Med. 1989; 170:1175-89.
  7. Wallis R, Shaw JM, Uitdehaag J, Chen CB, Torgersen D, et al. Localization of the serine protease-binding sites in the collagen-like domain of mannose-binding protein: indirect effects of naturally occurring mutations on protease binding and activation J Biol Chem. 2004; 279:14065-73.
  8. Madsen HO, Garred P, Kurtzhals JA, Lamm LU, Ryder LP, et al. A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein. Immunogenetics. 1994; 40: 37-44.
  9. Dong M, Xu S, Oliveira CL, Pedersen JS, Thiel S, et al. Conformational changes in mannan-binding lectin bound to ligand surfaces. J Immunol. 2007; 178:3016-22.
  10. Heitzeneder S, Seidel M, Förster-Waldl E, Heitger A. Mannan-binding lectin deficiency - Good news, bad news, doesn't matter? Clin Immunol. 2012; 143: 22-38.
  11. Fujita T. Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol. 2002; 2:346-53.
  12. Møller-Kristensen M, Thiel S, Sjöholm A, Matsushita M, Jensenius JC. Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway Int Immunol. 2007; 19:141-9.
  13. Chen CB, Wallis R. Two mechanisms for mannose-binding protein modulation of the activity of its associated serine proteases. J Biol Chem. 2004; 279:26058-65.
  14. Super M, Thiel S, Lu J, Levinsky RJ, Turner MW Association of low levels of mannan-binding protein with a common defect of opsonisation. Lancet 1989; 2(8674):1236-9.
  15. Sumiya M, Super M, Tabona P, Levinsky RJ, Arai T, et al. Molecular basis of opsonic defect in immunodeficient children. Lancet. 1991; 337:1569-70.
  16. Lipscombe RJ, Beatty DW, Ganczakowski M, Goddard EA, Jenkins T, et al. Mutations in the human mannose-binding protein gene: frequencies in several population groups. Eur J Hum Genet. 1996; 4:13-9.
  17. Altorjay I, Vitalis Z, Tornai I, Palatka K, Kacska S, et al. Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis. J Hepatol. 2010; 53:484-91.
  18. Minchinton RM, Dean MM, Clark TR, Heatley S, Mullighan CG. Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an Australian blood donor population. Scand J Immunol. 2002; 56:630-41.
  19. Aittoniemi J, Koskinen S, Laippala P, Laine S, Miettinen A. The significance of IgG subclasses and mannan-binding lectin (MBL) for susceptibility to infection in apparently healthy adults with IgA deficiency. Clin Exp Immunol. 1999; 116:505-8.
  20. Saevarsdottir S, Ding B, Steinsson K, Grondal G, Valdimarsson H, et a l. Mannan Binding Lectin (MBL) genotypes coding for high MBL serum levels are associated with rheumatoidfactor negative rheumatoid arthritis in never smokers. Arthritis Res Ther. 2011; 13: R65.
  21. Zanetti KA, Haznadar M, Welsh JA, Robles AI, Ryan BM, et al. 3'-UTR and functional secretor haplotypes in mannose-binding lectin 2 are associated with increased colon cancer risk in African Americans. Cancer Res. 2012; 72:1467-77.
  22. Esmat S, Omran D, Sleem GA, Rashed L. Serum mannan-binding lectin in egyptian patients with chronic hepatitis C: its relation to disease progression and response to treatment. Hepat Mon. 2012; 12: 259-64.
  23. Ip WK, To YF, Cheng SK, Lau YL. Serum mannose-binding lectin levels and mbl2 gene polymorphisms in different age and gender groups of southern Chinese adults. Scand J Immunol. 2004; 59: 310-4.
  24. Chen J, Xu Z, Ou X, Wang M, Yang X, et al. Mannose-binding lectin polymorphisms and recurrent respiratory tract infection in Chinese children. Eur J Pediatr. 2009; 168: 1305-13.
  25. Ou X, Li Q, Wang M, Chen J, Wang LJ, et al. Determination of the serum mannose binding lectin levels in 738 Han ethnic group children. Zhonghua Er Ke Za Zhi. 2008; 46: 610-2.
  26. Cosar H, Ozkinay F, Onay H, Bayram N, Bakiler AR, et al. Low levels of mannose-binding lectin confers protection against tuberculosis in Turkish children. Eur J Clin Microbiol Infect Dis. 2008; 27: 1165-9.
  27. Gergely P Jr, Pazár B, Nagy ZB, Gombos T, Rajczy K, et al. Structural polymorphisms in the mannose-binding lectin gene are associated with juvenile idiopathic arthritis. J Rheumatol. 2009; 36: 843-7.
  28. Dolman KM, Brouwer N, Frakking FN, Flatø B, Tak PP, et al. Mannose-bnding lectin deficiency is associated with early onset of polyarticular juvenile rheumatoid arthritis: a cohort study. Arthritis Res Ther. 2008; 10: R32.
  29. Tao R, Hua CZ, Hu YZ, Shang SQ. Genetic polymorphisms and serum levels of mannose-binding lectin in Chinese pediatric patients with common infectious diseases. Int J Infect Dis. 2012; 16: e403-7.
  30. Bak-Romaniszyn L, Szala A, Sokolowska A, Mierzwa G, Czerwionka-Szaflarska M, et al. Mannan-binding lectin deficiency in pediatric patients with inflammatory bowel disease. Scand J Gastroenterol. 2011; 46:1275-8.
  31. Israëls J, Frakking FN, Kremer LC, Offringa M, Kuijpers TW, et al. Mannose-binding lectin and infection risk in newborns: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2010;95: F452-61.
  32. Garred P, Larsen F, Seyfarth J, Fujita R, Madsen HO. Mannose-binding lectin and its genetic variants. Genes Immun. 2006; 7:85-94.
  33. Aittoniemi J, Miettinen A, Laippala P, Isolauri E, Viikari J, et al. Age-dependent variation in the serum concentration of mannan-binding protein. Acta Paediatr. 1996; 85: 906-9.
  34. Frakking FN, Brouwer N, Zweers D, Merkus MP, Kuijpers TW, Offringa M, et al. High prevalence of mannose-binding lectin (MBL) deficiency in premature neonates. Clin Exp Immunol. 2006; 145: 5-12.
  35. Potlukova E, Jiskra J, Freiberger T, Limanova Z, Zivorova D, et al. The production of mannan-binding lectin is dependent upon thyroid hormones regardless of the genotype: a cohort study of 95 patients with autoimmune thyroid disorders. Clin Immunol. 2010; 136: 123-9.
  36. Pana ZD, Samarah F, Papi R, Antachopoulos C, Papageorgiou T, et al. Mannose binding lectin and ficolin-2 polymorphisms are associated with increased risk for bacterial infections in children with B acute lymphoblastic leukemia. Pediatr Blood Cancer. 2014; 61: 1017-22.
  37. Eisen DP, Dean MM, Boermeester MA, Fidler KJ, Gordon AC, et al. Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection. Clin Infect Dis. 2008; 47: 510-6.
  38. Valdimarsson H, Stefansson M, Vikingsdottir T, Arason GJ, Koch C, et al. Reconstitution of opsonizing activity by infusion of mannan-binding lectin (MBL) to MBL deficient humans. Scand J Immunol. 1998; 48:116-23.
  39. Valdimarsson H. Infusion of plasma-derived mannan-binding lectin (MBL) into MBL-deficient humans. Biochem Soc Trans. 2003; 31:768-9.
  40. Jensenius JC, Jensen PH, McGuire K, Larsen JL, Thiel S. Recombinant mannan-binding lectin (MBL) for therapy. Biochem Soc Trans. 2003; 31:763-7.
  41. Petersen KA, Matthiesen F, Agger T, Kongerslev L, Thiel S, et al. Phase I safety, tolerability, and pharmacokinetic study of recombinant human mannan-binding lectin. J Clin Immunol. 2006; 26: 465-75.
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