Mannose-binding Lectin (MBL)

CPT: 83520
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Test Details

Use

The determination of MBL concentrations in serum may be useful for the elucidation of suspected immune defects and as a prognostic indicator alerting to the need for heightened therapeutic or prophylactic measures in immunosuppressed patients, including patients receiving cancer chemotherapy and patients with cystic fibrosis, SLE, or rheumatoid arthritis.

Limitations

Results of this test are labeled for research purposes only by the assay's manufacturer. The performance characteristics of this assay have not been established by the manufacturer. The result should not be used for treatment or for diagnostic purposes without confirmation of the diagnosis by another medically established diagnostic product or procedure. The performance characteristics were determined by LabCorp.

Methodology

Enzyme-linked immunosorbent assay (ELISA) using microwells coated with the unique monoclonal antibody to capture MBL via an epitope near its carbohydrate-binding site. Bound MBL is detected with the same antibody that has been labeled with biotin.

Additional Information

Mannose-binding lectin (MBL) is a multimeric, carbohydrate-binding protein produced in the liver and secreted into the blood that plays an important role in the innate immune response against invading microörganisms.1-6 MBL is a member of a family of the "collections" proteins, so named because they have a collagen-like region and a lectin region. Functional MBL is an oligomer complex of three identical monomer chains connected together through a triple helix of the collagen-like regions. The three C-terminal lectin carbohydrate recognition domains of the individual component proteins stick out from the triple helix in a manner that, by electron microscopy, resembles three flowers protruding from a single stalk. Many pathogens, including viruses, bacteria, fungi, protozoa, have surface sugars that are absent from mammalian cell surfaces. The lectin domains of the MBL complex recognize the spatial arrangement of carbohydrate sugar residues on pathogen surfaces and bind to them. Specific enzymes (MBL-associated serine proteases or MASPs) are activated when MBL binds to microbial carbohydrate surfaces and in turn activate complement via the MBL or lectin pathway. MBL binding to pathogens surfaces activates the complement system, causing inflammation, increased vascular permeability, and the recruitment and activation of phagocytes. MBL binding also facilities recognition and ingestion of the foreign entity by phagocytes in a process referred to as opsonization.

Only the normally oligomerized forms of MBL are capable of binding efficiently to the microbial carbohydrates and associating with the MASPs, thus activating complement via the lectin pathway. Diminished MBL levels can occur due to allelic variants in the promoter and/or structural regions of the MBL gene. Certain promoter alleles are associated with lower serum concentrations of MBL, while the structural variants impair both normal oligomerization of MBL and total chain synthesis.7 Subjects who are homozygous for a structural defect show very low levels of oligomerized MBL (<50 ng/mL), while heterozygotes show low-intermediate levels (50−500 ng/mL). In 100 healthy Danish blood donors, serum MBL concentrations determined by an oligomer-selective immunoassay showed low values (<50 ng/mL) in 12 individuals.8 Sallenbach and coworkers measured the MBL serum concentration in 631 apparently healthy subjects.9 The median MBL serum concentration was 1340 ng/mL (range, <5-12,200). Results were below the detection limit in 40 (11.4%) of 350 adults, in 1 of 141 preterm, and in 1 of 20 term neonates.9 Eisen and coworkers suggested that a cutoff of 500 ng/mL would be an appropriate threshold for identifying patients with MBL-deficient genotypes.10

Most individuals with diminished levels of normally oligomerized MBL are healthy with no clinical evidence of immune deficiency.11 While the consequences of MBL deficiency can be quite subtle, several studies have shown that MBL deficiency increases the overall susceptibility of an individual to infectious disease and predisposes to greater severity when infections occur. Decreased MBL levels may be associated with increased susceptibility to infections when the adaptive immune system is immature (in early childhood)12 or has been suppressed after organ transplantation13-15 or during cancer chemotherapy.16,17 In adults, MBL may play a role in determining host susceptibility to infection, pathogenesis, and progression of disease, and may contribute to the variability of host response to infection.10,18-20

Studies also suggest that individuals with relatively low MBL may suffer from more severe courses of autoimmune diseases such as systemic lupus erythematosus21,22 or rheumatoid arthritis,23 and from poorer prognoses in cystic fibrosis.24 Recurrent spontaneous abortions are reported to be correlated with low serum MBL levels.25,26 It has also been shown that low serum MBL levels have a negative impact on pregnancy outcome in women with a history of unexplained recurrent spontaneous abortion.27

Specimen Requirements

Specimen

Gel-barrier tube or red-top tube

Volume

0.5 mL

Minimum Volume

0.1 mL (Note: This volume does not allow for repeat testing.)

Patient Preparation

No special patient preparations are necessary.

Collection

If a red-top tube is used, transfer separated serum to a plastic transport tube.

Storage Instructions

Maintain specimen at room temperature. Stable 14 days. Stable refrigerated or frozen for 14 days. Freeze/thaw cycles: stable x3.

Causes for Rejection

Nonserum sample; hemolyzed or hyperlipemic sample received

Clinical Information

Footnotes

1. Turner MW. The role of mannose-binding lectin in health and disease. Mol Immunol. 2003 Nov; 40(7):423-429. 14568388
2. Sorensen R, Thiel S, Jensenius JC. Mannan-binding-lectin-associated serine proteases, characteristics and disease associations. Springer Semin Immunopathol. 2005 Nov; 27(3):299-319. 16189649
3. Takahashi K, Ezekowitz RA. The role of the mannose-binding lectin in innate immunity. Clin Infect Dis. 2005 Nov 15; 41(Suppl 7):S440-S444. 16237644
4. Worthley DL, Bardy PG, Gordon DL, et al. Mannose-binding lectin and maladies of the bowel and liver. World J Gastroenterol. 2006 Oct 28;12(40):6420-6428. 17072973
5.Ip WK, Takahashi K, Ezekowitz RA, Stuart LM. Mannose-binding lectin and innate immunity. Immunol Rev. 2009 Jul; 230(1):9-21. 19594626
6. Pettigrew HD, Teuber SS, Gershwin ME. Clinical significance of complement deficiencies. Ann NY Acad Sci. 2009 Sep;1173:108-123. 19758139
7. Larsen F, Madsen HO, Sim RB, Koch C, Garred P. Disease-associated mutations in human mannose-binding lectin compromise oligomerization and activity of the final protein. J Biol Chem. 2004 May 14; 279(20):21302-21311. 14764589
8. Steffensen R, Thiel S, Varming K, Jersild C, Jensenius JC.. Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers. J Immunol Methods. 2000 Jul 31; 241(1-2):33-42. 10915847
9. Sallenbach S, Thiel S, Aebi C, et al. Serum concentrations of lectin-pathway components in healthy neonates, children and adults: mannan-binding lectin (MBL), M-, L-, and H-ficolin, and MBL-associated serine protease-2 (MASP-2). Pediatr Allergy Immunol. 2011 Jun; 22(4):424-430.
10. Eisen S, Dzwonek A, Klein NJ. Mannose-binding lectin in HIV infection. Future Virol. 2008 May; 3(3):225-233. 21218140
11. Thiel S, Frederiksen PD, Jensenius JC. Clinical manifestations of mannan-binding lectin deficiency. Mol Immunol. 2006 Jan; 43(1-2):86-96. 16023210
12. Israëls J, Frakking FN, Kremer LC, Offringa M, Kuijpers TW, van de Wetering MD. Mannose-binding lectin and infection risk in newborns: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2010 Nov; 95(6):F452-F461. 20488866
13. Bouwman LH, Roos A, Terpstra OT, et al. Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation. Gastroenterology. 2005 Aug; 129(2):408-414.16083697
14. Worthley DL, Johnson DF, Eisen DP, et al. Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation. Clin Infect Dis. 2009 Feb 15; 48(4):410-417. 19143554
15. Bay JT, Sørensen SS, Hansen JM, Madsen HO, Garred P.. Low mannose-binding lectin serum levels are associated with reduced kidney graft survival. Kidney Int. 2013 Feb; 83(2):264-271. 23172101
16. Peterslund NA, Koch C, Jensenius JC, Thiel S. Association between deficiency of mannose-binding lectin and severe infections after chemotherapy. Lancet. 2001 Aug 25; 358(9282):637-638. 11530153
17. Neth O, Hann I, Turner MW, Klein NJ. Deficiency of mannose-binding lectin and burden of infection in children with malignancy: A prospective study. Lancet. 2001 Aug 25; 358(9282):614-618. 11530147
18. Eisen DP. Mannose-binding lectin deficiency and respiratory tract infection. J Innate Immun. 2010; 2(2):114-122. 20375630
19. Eisen DP, Dean MM, Thomas P, et al. Low mannose-binding lectin function is associated with sepsis in adult patients. FEMS Immunol Med Microbiol. 2006; 48:274-282.
20. Rantala A, Lajunen T, Juvonen R, et al. Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men. J Infect Dis. 2008 Oct 15;198(8):1247-1253. 18729778
21. Øhlenschlaeger T, Garred P, Madsen HO, Jacobsen S. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med. 2004 Jul 15; 351(3):260-267. 15254284
22. Saevarsdottir S, Kristjansdottir H, Grondal G, Vikingsdottir T, Steinsson K, Valdimarsson H. Mannan-binding lectin and complement C4A in Icelandic multicase families with systemic lupus erythematosus. Ann Rheum Dis. 2006 Nov; 65(11):1462-1467. 16439442
23. Bouwman LH, Roep BO, Roos A. Mannose-binding lectin: Clinical implications for infection, transplantation, and autoimmunity. Hum Immunol. 2006 Apr-May; 67(4-5):247-256. 16720204
24. Chalmers JD, Fleming GB, Hill AT, Kilpatrick DC. Impact of mannose-binding lectin insufficiency on the course of cystic fibrosis: A review and meta-analysis. Glycobiology. 2011 Mar; 21(3):271-282. 21045008
25. Christiansen OB, Kilpatrick DC, Souter V, Varming K, Thiel S, Jensenius JC. Mannan-binding lectin deficiency is associated with unexplained recurrent miscarriage. Scand J Immunol. 1999 Feb; 49(2):193-196. 10075024
26. Christiansen OB, Nielsen HS, Lund M, Steffensen R, Varming K. Mannose-binding lectin-2 genotypes and recurrent late pregnancy losses. Hum Reprod. 2009 Feb; 24(2):291-299. 18927129
27. Kruse C, Rosgaard A, Steffensen R, Varming K, Jensenius JC, Christiansen OB. Low serum level of mannan-binding lectin is a determinant for pregnancy outcome in women with recurrent spontaneous abortion. Am J Obstet Gynecol. 2002 Nov; 187(5):1313-1320. 12439525

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
004900 Mannose Binding Lectin (MBL) 004901 Mannose Binding Lectin (MBL) ng/mL 30152-3
Reflex Table for Mannose Binding Lectin (MBL)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 146716 Comment: 146716 Comment: N/A

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