Abstract
Heavy Chain Disease (HCD) is a group of rare B-cell proliferative disorders. Diagnosis depends on the detection of a truncated heavy chain with no associated light chain, often done by serum or urine immunofixation. This approach has been reported to have low specificity, since associated light chain bands are sometimes not visible and heavy chain bands can be mistaken for polyclonal bands. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) offers improved sensitivity in detecting monoclonal immunoglobulins. Truncation is thought to happen in the constant heavy chain (CH1) region, detected as a fragment of mass 27,000 Da on MALDI-TOF. Other mass patterns have not been reported in the literature. In this study, frozen serum samples from 8 heavy chain disease patients were analyzed by MALDI-TOF mass spectrometry. Spectra were reviewed on Mass-Fix software and visually inspected for monoclonal peaks. We detected two types of patterns for the IgG heavy chain disease. One pattern shows an IgG heavy chain with truncated mass (27,000 Da vs. 50,000 Da) and another in which the mass of the IgG heavy chain is greater than normal (65,000 Da). Follow-up work demonstrates that these are most likely dimers of truncated heavy chains. Thus, mass spectrometry-based immunofixation can provide new insights into heavy chain disease biology, mechanism, and progression, which are not identified by traditional diagnostic methods.