Holotranscobalamin, a marker of vitamin B-12 status: Analytical aspects and clinical utility

American Journal of Clinical Nutrition

Volumn 94, Issue 1, 2011, Pages

  Nexo, Ebba ^a   Hoffmann Lücke, Elke ^a  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CREATININE; CYANOCOBALAMIN; EDETIC ACID; HAPTOCORRIN; HOLOTRANSCOBALAMIN; HOMOCYSTEINE; METHYLMALONIC ACID; PYRIDOXINE; THIAMINE; TRANSCOBALAMIN; UNCLASSIFIED DRUG;

BLOOD SAMPLING; BLOOD STORAGE; CIRCADIAN RHYTHM; CONFERENCE PAPER; CREATININE BLOOD LEVEL; CYANOCOBALAMIN DEFICIENCY; ENZYME LINKED IMMUNOSORBENT ASSAY; GENOTYPE; HUMAN; LIFE CYCLE; METHYLMALONIC ACIDEMIA; PRECIPITATION; PREDICTIVE VALUE; PREGNANT WOMAN; PROTEIN BINDING; PYRIDOXINE DEFICIENCY; RACE DIFFERENCE; RADIOIMMUNOASSAY; REFERENCE VALUE; SEX DIFFERENCE; TRANSCOBALAMIN DEFICIENCY; VITAMIN BLOOD LEVEL; VITAMIN INTAKE; VITAMIN METABOLISM;

BIOLOGICAL MARKERS; CIRCADIAN RHYTHM; FEMALE; HOMOCYSTEINE; HUMANS; MALE; METHYLMALONIC ACID; TRANSCOBALAMINS; VITAMIN B 12; VITAMIN B 12 DEFICIENCY;

EID: 79959460458     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.111.013458     Document Type: Conference Paper

References (61)

1. Herzlich B, Herbert V. Depletion of serum holotranscobalamin II. An early sign of negative vitamin B12 balance. Lab Invest 1988;58:332-7.
2. Nexo E, Andersen J. Unsaturated and cobalamin saturated transcobalamin I and II in normal human plasma. Scand J Clin Lab Invest 1977;37:723-8. (Pubitemid 8387603)
3. Hom BL, Olesen HA. Plasma clearance of 57cobalt-labelled vitamin B12 bound in vitro and in vivo to transcobalamin I and II. Scand J Clin Lab Invest 1969;23:201-11.
4. Nexo E, Gimsing P. Turnover in humans of iodine- and cobalamin-labeled transcobalamin I and of iodine-labeled albumin. Scand J Clin Lab Invest 1975;35:391-8.
5. Kolhouse JF, Kondo H, Allen NC, Podell E, Allen RH. Cobalamin analogues are present in human plasma and can mask cobalamin deficiency because current radioisotope dilution assays are not specific for true cobalamin. N Engl J Med 1978;299:785-92. (Pubitemid 9044521)
6. Hardlei TF, Nexo E. A new principle for measurement of cobalamin and corrinoids, used for studies of cobalamin analogs on serum haptocorrin. Clin Chem 2009;55:1002-10.
7. Carmel R. R-binder deficiency. A clinically benign cause of cobalamin pseudodeficiency. JAMA 1983;250:1886-90.
8. Morkbak AL, Pedersen JF, Nexo E. Glycosylation independent measurement of the cobalamin binding protein haptocorrin. Clin Chim Acta 2005;356:184-90. (Pubitemid 40779901)
9. Refsum H, Johnston C, Guttormsen AB, Nexo E. Holotranscobalamin and total transcobalamin in human plasma: determination, determinants, and reference values in healthy adults. Clin Chem 2006;52:129-37. (Pubitemid 43032476)
10. Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr 2011;94(suppl):nn-nn.
11. Herbert V. Staging vitamin B-12 (cobalamin) status in vegetarians. Am J Clin Nutr 1994;59(suppl):1213S-22S.
12. Lloyd-Wright Z, Hvas AM, Møller J, Sanders TA, Nexo E. Holotranscobalamin as an indicator of dietary vitamin B12 deficiency. Clin Chem 2003;49:2076-8. (Pubitemid 37449481)
13. Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr 2003;78:131-6. (Pubitemid 39655258)
14. Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004;50:3-32. (Pubitemid 38125696)
15. Green R, Miller JW. Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population. Clin Chem Lab Med 2005;43:1048-51. (Pubitemid 41581959)
16. Hvas AM, Nexo E. Diagnosis and treatment of vitamin B12 deficiency-an update. Haematologica 2006;91:1506-12. (Pubitemid 44736117)
17. Bor MV, von Castel-Roberts KM, Kauwell GP, et al. Daily intake of 4 to 7 lg dietary vitamin B-12 is associated with steady concentrations of vitamin B-12-related biomarkers in a healthy young population. Am J Clin Nutr 2010;91:571-7.
18. Begley JA, Hall CA. Measurement of vitamin B12-binding proteins of plasma. I. Technique. Blood 1975;45:281-6.
19. van Kapel J, Wouters NM, Lindemans J. Application of heparin-conjugated Sepharose for the measurement of cobalamin-saturated and unsaturated transcobalamin II. Clin Chim Acta 1988;172:297-310. (Pubitemid 18085032)
20. Lindgren A, Kilander A, Bagge E, Nexo E. Holotranscobalamin: a sensitive marker of cobalamin malabsorption. Eur J Clin Invest 1999;29:321-9. (Pubitemid 29188825)
21. Lindemans J, Schoester M, van Kapel J. Application of a simple immunoadsorption assay for the measurement of saturated and unsaturated transcobalamin II and R-binders. Clin Chim Acta 1983;132:53-61. (Pubitemid 13069697)
22. Ulleland M, Eilertsen I, Quadros EV, et al. Direct assay for cobalamin bound to transcobalamin (holo-transcobalamin) in serum. Clin Chem 2002;48:526-32. (Pubitemid 34174583)
23. Nexo E, Christensen AL, Hvas AM, Petersen TE, Fedosov SN. Quantification of holo-transcobalamin, a marker of vitamin B12 deficiency. Clin Chem 2002;48:561-2. (Pubitemid 34174588)
24. Morkbak AL, Heimdal RM, Emmens K, et al. Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project. Clin Chem Lab Med 2005;43:1058-64. (Pubitemid 41581961)
25. Orning L, Rian A, Campbell A, et al. Characterization of a monoclonal antibody with specificity for holo-transcobalamin. Nutr Metab (Lond) 2006;3:3.
26. Brady J, Wilson L, McGregor L, Valente E, Orning L. Active B12: a rapid, automated assay for holotranscobalamin on the Abbott Ax-SYM analyzer. Clin Chem 2008;54:567-73. (Pubitemid 351348161)
27. Bamonti F, Moscato GA, Novembrino C, et al. Determination of serum holotranscobalamin concentrations with the AxSYM active B(12) assay: cut-off point evaluation in the clinical laboratory. Clin Chem Lab Med 2010;48:249-53.
28. Loikas S, Löppönen M, Suominen P, et al. RIA for serum holotranscobalamin: method evaluation in the clinical laboratory and reference interval. Clin Chem 2003;49:455-62. (Pubitemid 36250206)
29. Hvas AM, Gravholt CH, Nexo E. Circadian variation of holotranscobalamin (holo-TC) and related markers. Clin Chem Lab Med 2005;43:760-4. (Pubitemid 41461184)
30. von Castel-Roberts KM, Morkbak AL, Nexo E, et al. Holotranscobalamin is an indicator of vitamin B-12 absorption in healthy adults with adequate vitamin B-12 status. Am J Clin Nutr 2007;85:1057-61. (Pubitemid 46557921)
31. Nexo E, Christensen AL, Petersen TE, Fedosov SN. Measurement of transcobalamin by ELISA. Clin Chem 2000;46:1643-9.
32. Hvas AM, Nexo E. Holotranscobalamin - a first choice assay for diagnosing early vitamin B12 deficiency? J Intern Med 2005;257:289-98.
33. Morkbak AL, Hvas AM, Milman N, Nexo E. Holotranscobalamin remains unchanged during pregnancy. Longitudinal changes of cobalamins and their binding proteins during pregnancy and postpartum. Haematologica 2007;92:1711-2.
34. Murphy MM, Molloy AM, Ueland PM, et al. Longitudinal study of the effect of pregnancy on maternal and fetal cobalamin status in healthy women and their offspring. J Nutr 2007;137:1863-7. (Pubitemid 47292731)
35. Nexo E, Hvas AM, Bleie Ø, et al. Holo-transcobalamin is an early marker of changes in cobalamin homeostasis. A randomized placebo-controlled study. Clin Chem 2002;48:1768-71.
36. Nexo E, Hollenberg MD. Characterization of the particulate and soluble acceptor for transcobalamin II from human placenta and rabbit liver. Biochim Biophys Acta 1980;628:190-200. (Pubitemid 10097243)
37. Quadros EV, Nakayama Y, Sequeira JM. The binding properties of the human receptor for the cellular uptake of vitamin B12. Biochem Biophys Res Commun 2005;327:1006-10. (Pubitemid 40137967)
38. Quadros EV, Nakayama Y, Sequeira JM. The protein and the gene encoding the receptor for the cellular uptake of transcobalamin-bound cobalamin. Blood 2009;113:186-92.
39. Li N, Sood GK, Seetharam S, Seetharam B. Polymorphism of human transcobalamin II: substitution of proline and/or glutamine residues by arginine. Biochim Biophys Acta 1994;1219:515-20. (Pubitemid 24319714)
40. Castro R, Barroso M, Rocha M, et al. The TCN2 776CNG polymorphism correlates with vitamin B(12) cellular delivery in healthy adult populations. Clin Biochem 2010;43:645-9.
41. Garrod MG, Allen LH, Haan MN, Green R, Miller JW. Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics. Eur J Clin Nutr 2010;64:503-9.
42. Platica O, Janeczko R, Quadros EV, Regec A, Romain R, Rothenberg SP. The cDNA sequence and the deduced amino acid sequence of human transcobalamin II show homology with rat intrinsic factor and human transcobalamin I. J Biol Chem 1991;266:7860-3. (Pubitemid 21906444)
43. Carmel R, Vasireddy H, Aurangzeb I, George K. High serum cobalamin levels in the clinical setting-clinical associations and holotranscobalamin changes. Clin Lab Haematol 2001;23:365-71. (Pubitemid 34093997)
44. Nexø E. Transcobalamin I and other human R-binders: purification, structural, spectral and physiological studies. Scand J Haematol 1978;20:221-36.
45. Loikas S, Koskinen P, Irjala K, et al. Renal impairment compromises the use of total homocysteine and methylmalonic acid but not total vitamin B12 and holotranscobalamin in screening for vitamin B12 deficiency in the aged. Clin Chem Lab Med 2007;45:197-201. (Pubitemid 46294679)
46. Moller HJ, Moestrup SK, Weis N, et al. Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163. Crit Care Med 2006;34:2561-6. (Pubitemid 44413053)
47. Baker H, Leevy CB, DeAngelis B, Frank O, Baker ER. Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue in alcoholics with liver disease. J Am Coll Nutr 1998;17:235-8.
48. Skouby AP, Hippe E, Olesen H. Antibody to transcobalamin II and B12 binding capacity in patients treated with hydroxocobalamin. Blood 1971;38:769-74.
49. Carmel R, Tatsis B, Baril L. Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood. Blood 1977;49:987-1000. (Pubitemid 8123866)
50. Aarsetøy H, Valente E, Reine A, Mansoor MA, Grundt H, Nilsen DW. Holotranscobalamin and methylmalonic acid as prognostic markers following an acute myocardial infarction. Eur J Clin Nutr 2008;62:411-8. (Pubitemid 351356582)
51. Nissen PH, Nordwall M, Hoffmann-Lücke E, Sorensen BS, Nexo E. Transcobalamin deficiency caused by compound heterozygosity for two novel mutations in the TCN2 gene: a study of two affected siblings, their brother, and their parents. J Inherit Metab Dis (Epub ahead of print 6 July 2010).
52. Bleie Ø, Refsum H, Ueland PM, et al. Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention. Am J Clin Nutr 2004;80:641-8.
53. Hvas AM, Morkbak AL, Nexo E. Plasma holotranscobalamin compared with plasma cobalamins for assessment of vitamin B12 absorption; optimisation of a non-radioactive vitamin B12 absorption test (CobaSorb). Clin Chim Acta 2007;376:150-4. (Pubitemid 44880994)
54. Bor MV, Cetin M, Aytaç S, Altay C, Nexo E. Nonradioactive vitamin B12 absorption test evaluated in controls and in patients with inherited malabsorption of vitamin B12. Clin Chem 2005;51:2151-5. (Pubitemid 41532633)
55. Hardlei TF, Mørkbak AL, Bor MV, Bailey LB, Hvas AM, Nexo E. Assessment of vitamin B(12) absorption based on the accumulation of orally administered cyanocobalamin on transcobalamin. Clin Chem 2010;56:432-6.
56. Clarke R, Sherliker P, Hin H, et al. Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin. Clin Chem 2007;53:963-70. (Pubitemid 46744255)
57. Herrmann W, Obeid R, Schorr H, Geisel J. Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med 2003;41:1478-88. (Pubitemid 37493564)
58. Obeid R, Herrmann W. Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid. Clin Chem Lab Med 2007;45:1746-50. (Pubitemid 350232986)
59. Schrempf W, Eulitz M, Neumeister V, Siegert G, Koch R, Reichmann H, Storch A. Utility of measuring vitamin B(12) and its active fraction, holotranscobalamin, in neurological vitamin B(12) deficiency syndromes. J Neurol (Epub ahead of print 2 October 2010).
60. Miller JW, Garrod MG, Rockwood AL, et al. Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency. Clin Chem 2006;52:278-85. (Pubitemid 43185490)
61. Fedosov SN. Metabolic signs of vitamin B(12) deficiency in humans: computational model and its implications for diagnostics. Metabolism 2010;59:1124-38.