gamma- and mu-Heavy chain diseases and related disorders.

Abstract

During the last ten years studies of myeloma proteins have shown them to be similar to or identical with normal immunoglobulins. In addition, the not infrequent occurrence of structural variants of immunoglobulins in association with neoplasms of lymphocytes or plasma cells has become widely recognized. Since the discovery of the group of heavy chain diseases in man (Franklin, Meltzer, Guggenheim, and Lowenstein, 1963; Franklin, Lowenstein, Bigelow, and Meltzer, 1964) and shortly afterwards of half-molecule IgA proteins in the mouse (Potter and Kuff, 1964), many structural variants of both heavy and light chains have been recognized (see review by Franklin and Frangione, 1975). It seems likely that studies of these proteins will provide insights into the genetic control of immunoglobulins (Igs) which cannot be obtained from analyses of intact molecules. This report summarizes the clinical features of yand,t-heavy chain disease (HCD) and discusses some of the biochemical and biosynthetic studies which have clearly established that these abnormal proteins are products of disordered synthesis and not the result of degradation. In addition, several other structural abnormalities of heavy chains will be mentioned, excluding a-chain disease which is dealt with elsewhere. A detailed classification of the known alterations of heavy and light chains is given in a review by Franklin and Frangione (1975). Only alterations in man will be considered, although similar changes in heavy chains have recently been discovered in the mouse (Scharff, 1974; Milstein, Adetiegbo, Cowan, and Secher, 1974). In this article discussion will be limited to four major types: (1) heavy chain disease proteins; (2) myeloma proteins with altered heavy chains; (3) half-molecules; and (4) myelomas with degraded heavy chains.