Detection of free light chain monoclonal proteins co-migrating with intact monoclonal proteins in patients with monoclonal gammopathy.

BACKGROUND: In a small, but potentially significant proportion of patients with a monoclonal gammopathy, patients show the existence of an intact monoclonal (M-) protein co-migrating with a free light chain (FLC) M-protein. Using traditional methods for detection of monoclonal immunoglobulins, only the intact M-protein may be detectable, and hence the FLC M-proteins may be missed. METHODS: Immunofixation electrophoresis (IFE) using two different sets of antisera were compared (one detecting both free and bound FLC epitopes, and one detecting only the free FLC epitopes), alongside urine protein electrophoresis and the Freelite assay in order to ascertain the best methods of detecting both types of M-proteins in this subset of patients. RESULTS: A total of 2% of the patient population tested were shown to have a FLC M-protein migrating coincidentally with an intact M-protein. These were not detected by IFE using the widely utilised antisera to both free and bound FLC epitopes, and hence may have been missed during routine testing, but were detectable using the other methods. CONCLUSIONS: This study highlights the important finding that in some patients with both an intact and a FLC M-protein, the FLC M-protein may be missed during routine testing. In incidences where no corresponding urine sample is sent to the laboratory alongside the serum sample, we would suggest testing for the presence of FLC M-proteins in this subset of patients using the Freelite assay, if no urine sample can be obtained, to ensure all FLC M-proteins are appropriately detected.

Antineutrophil cytoplasmic antibodies: two cases of changing antigenic specificity.

The transformation of the antineutrophil cytoplasmic antibody (ANCA) specificity in the absence of specific drug treatment has not been reported in the literature. A few studies have suggested changes in the epitopes recognized by the ANCAs. We describe two patients who switched from myeloperoxidase-positive to PR3 (proteinase 3)-positive ANCA during the course of their disease process and subsequently remained unchanged. One patient developed ulcerative colitis following the appearance of PR3-ANCA while the other remains quiescent. Regular follow-up and close monitoring of ANCA specificity are essential. A change of specificity may indicate the development of a new ANCA-related disease.