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BUXBAUM ALICE ALEXANDER Definition and History Etiology and Pathogenesis Chronic Antigenic Stimulation Defective Immunoglobulin Molecules Clinical Features Gamma-Heavy-Chain Disease Alpha-Heavy-Chain Disease Mu-Heavy-Chain Disease Delta- and Epsilon-Heavy-Chain Disease Laboratory Features Detection of Abnormal Immunoglobulin Protein Therapy, Course, and Prognosis Gamma-Heavy-Chain Disease Alpha-Heavy-Chain Disease Mu-Heavy-Chain Disease Chapter References The heavy-chain diseases are rare B-cell proliferative disorders of varying degrees of malignancy.

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Immunoelectrophoresis or immunofixation of serum, urine, or secretory fluids or immunohistologic analysis of the proliferating cells establishes the diagnosis.The disorders were defined in terms of the production of structurally aberrant immunoglobulin molecules.Since the neoplastic cells displayed plasmacytic features, they were viewed as myeloma variants and studied for the insights they could provide to immunoglobulin structure.Serum proteins were modified after synthesis and did not contain any amino acids before the hinge. Dashed lines indicate likely structures for which sequence data are missing. indicates probable missing domain based on molecular weight and partial protein structure analysis. These include deleted V regions, missing CH1 domains, and the absence of associated light chains.

**Structures shown are deduced amino acid sequences determined by c DNA sequencing. V = variable region, D = diversity segment, J = joining region, H = hinge region, CH1, CH2, CH3, CH4 = constant regions of heavy chains, Memb. In the cases where amino acid or nucleotide-sequence data are available (Fig.

No light chains are associated with the defective heavy chains, which usually exist in the serum as disulfide-linked dimers.

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