Donato et al. draw attention to a new type of immunoglobulin measurement, i.e., immunoglobulin heavy chain/light chain (HLC) pairs. For decades, monoclonal immunoglobulins have been successfully monitored by serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE), a practice that has led to the assumption that there is little need for improvement. Yet, these tests are not quantitative in the strictest sense; they require skilled interpretation and cannot assess immune suppression of polyclonal immunoglobulins of the same isotype as the monoclonal immunoglobulin. These features contrast with those of serum free light chain (FLC) assays, in which κ/λ ratios are measured by immunoassays and polyclonal FLC suppression is an important part of their clinical utility. In a similar manner, HLC pairs provide benefits over SPEP and IFE. Thus, Donato et al. show that HLC ratios provide good sensitivity for monoclonality combined with numerical precision, allowing the patient to be monitored reliably. Importantly, the changing ratio was affected by varying immune suppression, suggesting that this feature may be an important aspect of tumor progression that is not normally considered.
From a clinical perspective, myeloma symptoms such as back pain, tiredness, weakness, and so forth are nonspecific, so reliable tests are necessary. In this patient, the authors demonstrated that the patient was unwell for many months, yet the conventional tests did not produce convincingly abnormal results. IgA disease is particularly challenging for SPEP analysis because broad bands often migrate with other serum proteins. HLC assays should have a useful role for such patients.
Remaining questions include whether isotype suppression is a constant feature of early relapse. If so, what is the trigger? A second question is whether HLC assays could replace IFE for identifying clonality and for monitoring, and whether the tests are useful for other monoclonal gammopathies. Early evidence in this and other reports (1, 2) suggests that HLC tests have an interesting clinical utility.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:
Employment or Leadership: A.R. Bradwell, The Binding Site Group.
Consultant or Advisory Role: None declared.
Stock Ownership: A.R. Bradwell, The Binding Site Group.
Honoraria: None declared.
Research Funding: None declared.
Expert Testimony: None declared.
- Received for publication May 23, 2011.
- Accepted for publication June 7, 2011.
- © 2011 The American Association for Clinical Chemistry