Challenges in the diagnosis of hypervitaminemia B12. Interference by immunocomplexes

Delgado, José A.; García, Maria I. Pastor; Jiménez, Nuria Márquez; Petit, Gemma Costa; Cànaves, Josep A. Pablo; Robles, Juan; Bauça, Josep Miquel

doi:10.1016/j.cca.2023.117267

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…Mainly in recent years, the term has frequently been used to indicate substances removed by a nonspecific precipitation methodology, such as polyethylene glycol (PEG). A decreased level of B12 following PEG precipitation has been reported in up to 45% of samples with initial B12 levels above 554 pmol/L, and this in turn led to the suggestion that such samples should undergo PEG precipitation prior to reporting a result for B12 [ 9 ]. However, the substances removed by PEG precipitation are unknown, as is the possible impact of such substances on B12 metabolism; see the next section for further discussion.…”

Section: “Macro-b12” As An Explanation For An Unexpectedly High Plasm...mentioning

confidence: 99%

“…B12 [9][10][11]. Much of these controversies are caused by an incomplete understanding of the nature of B12 and its binding proteins in blood plasma, as well as the analytical procedures employed for its analysis.…”

Section: Plasma B12 and Its Binding Proteinsmentioning

confidence: 99%

“…Others suggest a high level of B12 is misleading and is caused by analytical flaws, or the presence of an ill-defined inert “macro-B12” that can be removed by precipitation with polyethylene glycol (PEG) [ 6 , 7 , 8 ]. Some papers go so far as to suggest an algorithm involving PEG precipitation applied to all samples with an increased level of B12 [ 9 , 10 , 11 ]. Much of these controversies are caused by an incomplete understanding of the nature of B12 and its binding proteins in blood plasma, as well as the analytical procedures employed for its analysis.…”

Section: Introductionmentioning

confidence: 99%

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Macro-B12 and Unexpectedly High Levels of Plasma B12: A Critical Review

Fedosov,

Nexo

2024

Nutrients

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A low total plasma vitamin B12 supports a clinical suspicion of B12 deficiency, while the interpretation of an unexpectedly normal/high level is marred by controversies. Here, we critically review current knowledge on B12 in blood plasma, including the presence of the so-called “macro-B12”. The latter form is most often defined as the fraction of B12 that can be removed by precipitation with polyethylene glycol (PEG), a nonspecific procedure that also removes protein polymers and antibody-bound analytes. Plasma B12 includes B12 attached to transcobalamin and haptocorrin, and an increased concentration of one or both proteins almost always causes an elevation of B12. The total plasma B12 is measured by automated competitive binding assays, often incorrectly referred to as immunoassays, since the binding protein is intrinsic factor and not an antibody. An unexpectedly high level of B12 may be further explored using immunological measurements of haptocorrin and transcobalamin (optionally combined with e.g., size-exclusion chromatography). Nonspecific methods, such as PEG precipitation, are likely to give misleading results and cannot be recommended. Currently, the need for evaluation of a high B12 of unknown etiology is limited since other tests (such as measurements of methylmalonic acid) may better guide the diagnosis of B12 deficiency.

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Section: “Macro-b12” As An Explanation For An Unexpectedly High Plasm...mentioning

confidence: 99%

Section: Plasma B12 and Its Binding Proteinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Macro-B12 and Unexpectedly High Levels of Plasma B12: A Critical Review

Fedosov,

Nexo

2024

Nutrients

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“…It has been reported that almost 50% of samples with a high level of total B12 contain macro-B12, and that this in turn leads to an incorrect high level for total B12. 27 However, currently, it is unresolved whether this is correct-or caused by nonspecific methodologies used for detection of the so-called macro-B12.…”

Section: Use Of the Four B12-related Biomarkers In The Clinical Settingmentioning

confidence: 99%

Vitamin B12-Related Biomarkers

Nexo,

Parkner

2024

Food Nutr Bull

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Background: Adult vitamin B12 (B12) deficiency may present itself with nonspecific mainly neurological symptoms, and thus plasma biomarkers are often judged to be of major importance in the further diagnostic process. Four biomarkers are of special relevance: total B12, holotranscobalamin (the part of B12 bound to the active transport protein, transcobalamin, also named holoTC or active B12) and the 2 so-called metabolic markers that accumulate if B12 is lacking, methylmalonic acid (MMA) and homocysteine. Objective: This article briefly reviews the inherent limitation of biomarkers, discusses its use in establishing the diagnosis and cause of B12 deficiency, and when following or discontinuing treatment with B12. Methods: The review is based on published papers, but also on knowledge gained from working within the area. Conclusion: It is concluded that a combination of a B12 and a metabolic marker, for example, total B12 and MMA, may prove most useful in daily practice. An unexpectedly high level of total B12 is most often of no clinical importance, though sometimes related to the presence of underlying cancer. Measurement of total B12 is of limited value in patients on treatment with pharmacological doses of B12 but may be helpful if B12 treatment is discontinued.

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