Quantitative measurement of serum free light chain is an important part of the diagnosis and management of multiple myeloma and related disorders. Recent consensus guidelines (1) focus on screening for the presence of monoclonal immunoglobulin and monitoring treatment in patients with amyloidosis or oligosecretory disease. As we expand our use of this assay to monitoring patients with intact monoclonal immunoglobulin, it is clear that some technical limitations still need to be resolved. This clinical case study reminds us that one of the original drawbacks of nephelometric determinations—antigen excess—may be important when measuring serum free light chain.
Antigen excess is due to inhibition of immune complex formation in the presence of very high antigen concentrations (2). Although manufacturers have largely eliminated this problem in noncompetitive immunoassays by either the use of sequential incubations or increasing the amount of solid-phase antibody, these approaches are not feasible for nephelometric assays. Consequently, unless the instrument’s software is able to detect possible antigen excess, the laboratory must rule it out by repeating the analysis with a higher dilution. If antigen excess is present, the final result will be higher, paradoxically, because the inhibition of immune complex formation has been removed.
Although this problem has been described before with the serum free light chain assay, the authors of the case study provide important context by documenting its relatively low prevalence. This fact might indicate that it is not necessary to routinely test serum samples for free light chain at more than the initial dilution. As in all areas of laboratory medicine, however, no individual result should be interpreted without consideration of other results, as well as the clinical picture.
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 of Potential Conflicts of Interest: No authors decalred any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- © 2010 The American Association for Clinical Chemistry