Heavy chain disease

Heavy-Chain Disease. Rarely, unusual forms of IgG, IgA, or light chains polymerize and cause a similar syndrome with high blood viscosity. Heavy-chain diseases in which the paraprotein consists only of a heavy chain, usually incomplete, are rare conditions associated with lymphoid infiltration. The most common of these is a-chain disease, in which the intestine is infiltrated and severe malabsorption may be seen. 

However in concentrated urine, Bence Jones was found in 15 and halfmolecules in 3 others, leaving only 4 with no detected paraprotein in either serum or urine. The heavy-chain diseases also seem to be associated with soft-tissue plasmacytoma (see Section 7.6.5). The impression gained is that dedifferentiated immunoglobulin production (more Bence Jones, etc.) is commoner with extraosseous immunocytomata, and with more careful preoperative examination of urines such paraproteins may be found in most cases. 

Paraproteins are found in myeloma, in Waldenstrom s macroglobulinacmiu and in heavy chain diseases. Tliese tire malignant conditions. The paraproteins may arise from any of the immunoglobulin classes. Monoclonal light chaitis are produced in excess of heavy chains in 5()% of cases of myeloma, and in 13% of ca.ses only light... 

D. Sequences of Proteins Associated with Heavy Chain Disease ... 

Deletions of quite another type were found in two proteins of heavy chain disease investigated by Terry and Ein (114). Each appeared to lack completely the Ed segment the amino acid sequences were initiated at positions 221 and 225. The authors suggested the possibility that these proteins are products of enzymatic digestion, rather than of de novo synthesis. They also point out that protein Cra (Fig. 4.16) is somewhat heterogeneous at the N-terminus and could likewise have been subject to postsynthetic degradation. Certain other proteins of heavy chain disease, such as Zuc, appear homogeneous with respect to amino acid sequence. 

Fig. 4.16. Deletions identified in several proteins associated with heavy chain disease. From Frangione and Franklin (110). The original references are 112 (Meg), 113 (Gif), 1 IS (Cra), and 168 (Zuc). The recently determined structure of another such protein (Hal), with a deletion ending at position 252, is discussed in the text.

A number of examples of a gene deletion have been reported (152,164,168-170). This as well as duplication, can result from homologous but unequal crossing over. Deletions of the IgG3 cistron were found among members of several families and deletions of the IgG 1 cistron in other families. In a few instances the defect was associated with an immune deficiency disease [reviewed in (127)]. Deletions of portions of an H chain (heavy chain disease) are discussed in Chapter 4, Section VII. 

Suggestions that separate genes may control the hinge region and individual Ch domains were discussed in relation to the proteins associated with heavy chain disease (Chapter 4, Section VII). 

Heavy chain variants—Heavy chain disease proteins... 

Biosynthetic studies have indicated that under normal conditions, the synthesis of H and L chains is approximately balanced and that plasma cells secrete primarily complete Ig molecules. However, in certain diseased states, unbalanced synthesis can occur. The most commonly encountered is the production of free L chains, although in general, they do not have structural abnormalities. The first examples of a structurally altered immunoglobulin occurred in 1963 " with the recognition of the first patient with Heavy Chain Disease (HCD). While HCD still remains the most striking abnormality, a series of more subtly altered molecules have been described. 

Table 1.7 Some properties of y, a, and heavy chain disease proteins...

A disease in which there is a proliferating clone of immunoglobulin-producing cells (plasma cells or lymphocytes). Myeloma, macroglobulinaemia and heavy chain diseases are examples of such diseases and they are often characterized by the presence of an abnormal protein (a paraprotein) in the blood. 

See also heavy chain diseases, macroglobulinaemia, myeloma... 

Monoclonal increases. These result from the proliferation of a single type of immunoglobulin synthesizing cell, producing a single class and type of immunoglobulin, known as a paraprotein. Paraproteins are found in myeloma, Waldenstrom s macroglobulinaemia and heavy-chain diseases. 

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