Monitoring IgA multiple myeloma: immunoglobulin heavy/light chain assays

The use of electrophoresis to monitor monoclonal immunoglobulins migrating in the β fraction may be difficult because of their comigration with transferrin and complement proteins.

Immunoassays specific for IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, and IgMλ heavy/light chain (HLC) were validated for use in the clinical laboratory. We assessed sample stability, inter- and intraassay variability, linearity, accuracy, and reference intervals for all 6 assays. We tested accuracy by verifying that the sum of the concentrations for the HLC-pairs accounted for the total immunoglobulins in each of 129 healthy sera, and that the HLC-pair ratios (rHLCs) were outside the reference interval in 97% of 518 diagnostic multiple myeloma (MM) samples.

We assessed diagnostic samples and posttreatment sera in 32 IgG and 30 IgA patients for HLC concentrations, rHLC, and total immunoglobulins and compared these nephelometry results with serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE). In sample sets from patients with IgG MM, the sensitivity of SPEP was almost the same as for rHLC, and no additional advantage was conferred by running HLC assays. In pre- and posttreatment samples from patients with IgA MM, the SPEP, rHLC, and IFE identified clonality in 28%, 56%, and 61%, respectively. In addition, when M-spikes were quantifiable, the concentration of the involved HLC was linearly related to that of the SPEP M-spike, with a slope near 1.

The use of IgA HLC assays for monitoring β-migrating IgA monoclonal proteins can substitute for the combination of SPEP, IFE, and total IgA quantification.