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A human myeloma immunoglobulin G binding four moles of calcium associated with asymptomatic hypercalcemia

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Abstract

A calcium-binding immunoglobulin G (IgGIλRUP) 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 γ-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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Authors and Affiliations

  1. Department of Medicine, Columbia University College of Physicians and Surgeons, 10032, New York, New York

    Giampaolo Merlini, Lorraine A. Fitzpatrick, Ethel S. Siris, John P. Bilezikian, Steven Birken & Elliott F. Osserman

  2. Cancer Research Center/Institute of Cancer Research, Columbia University College of Physicians and Surgeons, 10032, New York, New York

    Giampaolo Merlini & Elliott F. Osserman

  3. Department of Pharmacology, Columbia University College of Physicians and Surgeons, 10032, New York, New York

    John P. Bilezikian

  4. Department of Biological Sciences and Chemistry, Columbia University, 10032, New York, New York

    Sherman Beychok

Authors
  1. Giampaolo Merlini
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  2. Lorraine A. Fitzpatrick
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  3. Ethel S. Siris
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  4. John P. Bilezikian
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  5. Steven Birken
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  6. Sherman Beychok
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  7. Elliott F. Osserman
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Merlini, G., Fitzpatrick, L.A., Siris, E.S. et al. A human myeloma immunoglobulin G binding four moles of calcium associated with asymptomatic hypercalcemia. J Clin Immunol 4, 185–196 (1984). https://doi.org/10.1007/BF00914965

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  • DOI: https://doi.org/10.1007/BF00914965

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