An IgG complexed form of vitamin B12 is a common cause of elevated serum concentrations

ObjectivesTo report detailed investigations in a case of elevated serum B12 due to the presence of an IgG–B12 complex, to determine the prevalence of this phenomenon and to review the literature.Design and methods431 samples with elevated B12 (median 1250 ng/L, range 901–114,480 ng/L) were treated with polyethylene glycol to precipitate immunoglobulin complexes. Samples with > 50% of precipitable B12 (PPB12) were further investigated by protein G adsorption, gel filtration chromatography and measurement of B12 on different analytical platforms.ResultsMedian PPB12 was 22.6%, but in 35 samples (8.1%), median PPB12 was more than 50%. Investigation of 27 of these samples with protein G-Sepharose confirmed the presence of an IgG–B12 complex in 24, and in 15 cases, B12 fell to within the reference range. After treatment of serum with reagents releasing B12 from binding proteins, immunoreactivity co-eluted with free B12. Immunoreactivity of the IgG-bound form of B12 was confirmed using five B12 assays in common use in the UK.ConclusionsAt least 8% of samples with elevated vitamin B12 contain an immunoglobulin complexed form of circulating B12; this possibility should be considered in the interpretation of results.