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

Objectives: To report detailed investigations in a case of elevated serum B(12) due to the presence of an IgG-B(12) complex, to determine the prevalence of this phenomenon and to review the literature.

Design and methods: 431 samples with elevated B(12) (median 1250 ng/L, range 901-114,480 ng/L) were treated with polyethylene glycol to precipitate immunoglobulin complexes. Samples with >50% of precipitable B(12) (PPB(12)) were further investigated by protein G adsorption, gel filtration chromatography and measurement of B(12) on different analytical platforms.

Results: Median PPB(12) was 22.6%, but in 35 samples (8.1%), median PPB(12) was more than 50%. Investigation of 27 of these samples with protein G-Sepharose confirmed the presence of an IgG-B(12) complex in 24, and in 15 cases, B(12) fell to within the reference range. After treatment of serum with reagents releasing B(12) from binding proteins, immunoreactivity co-eluted with free B(12). Immunoreactivity of the IgG-bound form of B(12) was confirmed using five B(12) assays in common use in the UK.

Conclusions: At least 8% of samples with elevated vitamin B(12) contain an immunoglobulin complexed form of circulating B(12); this possibility should be considered in the interpretation of results.