[Persistent very high levels of P-cobalamin caused by formation of immune complexes, macro-B12]

Supranormal plasma levels of cobalamin may result from formation of immune complexes of cobalamin bound to transcobalamin, referred to as macro-B12. Two patients with very high levels of B12, 3800 pmol/l and above 4400 pmol/l, were investigated. PEG precipitation decreased B12 levels to 175 pmol/l and 191 pmol/l, respectively. Employing protein G spin columns decreased levels by 92 procent and 87 procent, proving that the high levels of B12 were caused by formation of IgG-immune complexes. Macro-B12 may obscure underlying deficit of B12, since immune complex-bound holotranscobalamin is biologically inactive. Supranormal levels of vitamin B12 have been associated with myeloproliferative diseases, lymphoid malignancies, various types of cancer and hepatic and renal disease. In clinical literature it is recommended that supranormal levels of B12 (>1000 pmol/l) are investigated for malignancy or other underlying disease, but further research could define the conditions and clinical advantages of such investigations.