Spontaneous enzymatic cleavage of IgD myeloma protein giving a pattern of delta heavy chain disease.

The monoclonality of myeloma proteins is usually demonstrated by their electrophoretic homogeneity and their reactivity with monovalent antisera directed against isotypic determinants of a single heavy chain and a single type of light chain. The absence of precipitation with anti-sera to immunoglobulin kappa and Lambda light chains is a constant character of heavy Chain Disease Proteins (HCDP). However, homogeneous M-components present in the sera of some patients and reacting only with anti-heavy-chain antisera were identified as IgA and IgD myeloma proteins bearing unreactive Lambda chains. In this study, the electrophoretic pattern of a patient serum showed a paraprotein with heterogeneous electrophoretic mobility and precipitation reaction limited to anti-IgD antiserum. The failure to react with anti-light chain antisera was observed by immuno-electrophoresis, immunofixation and rocket-immunoselection. Further analysis by crossed-immunoelectrophoresis revealed that IgD paraprotein contained two separate populations of molecules, one of them being retained when anti-Kappa and Lambda light chains anti-bodies were incorporated in the first dimension gel. It soon became obvious that the observed pattern was generated by enzymatic cleavage of native IgD myeloma protein.