A human myeloma immunoglobulin G binding four moles of calcium associated with asymptomatic hypercalcemia |
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Authors: | Giampaolo Merlini Lorraine A Fitzpatrick Ethel S Siris John P Bilezikian Steven Birken Sherman Beychok Elliott F Osserman |
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Institution: | (1) Department of Medicine, Columbia University College of Physicians and Surgeons, 10032 New York, New York;(2) Cancer Research Center/Institute of Cancer Research, Columbia University College of Physicians and Surgeons, 10032 New York, New York;(3) Department of Pharmacology, Columbia University College of Physicians and Surgeons, 10032 New York, New York;(4) Department of Biological Sciences and Chemistry, Columbia University, 10032 New York, New York |
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Abstract: | A calcium-binding immunoglobulin G (IgGIRUP) was identified in the serum of a patient with multiple myeloma, asymptomatic hypercalcemia, and a normal ionized serum calcium. Calcium binding by IgGRUP was confirmed by two-dimensional electrophoresis with calcium-45 and equilibrium dialysis. Amino acid analyses indicated an unusually high number of glutamic (or glutamine) residues in the L chain and Fab fragment but no detectable -carboxyglutamic acid. As determined by equilibrium dialysis with45Ca, the intact IgGRUP and its Fab fragments bound calcium at an optimum pH of 7.4. There was minimal binding of calcium to H chains and no binding by L chains or the Fc fragment. Recombination of H and L chains partially restored the binding activity. By Scatchard analysis, the binding affinity (K
d) of IgGRUP was 1.7×10–3
M and the binding capacity was 4 mol of calcium/mol of IgG. The binding of 4 mol of calcium/mol of IgG is twice that reported previously for two other calcium-binding myeloma proteins and suggests unique properties of IgGRUP. |
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Keywords: | Myeloma IgG calcium binding |
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