For Immunoglobulin Light Chains, It's Time to Fly!

Multiple myeloma represents only approximately 10% of all hematopoietic malignancies but it is unusual in one respect: it announces itself early. Many years before the disease begins to cause symptoms, the tumor's calling card—its unique monoclonal protein—can be seen in the patient's serum. It takes some time for this monoclonal immunoglobulin to emerge from the normal polyclonal background and, even when it does, it can be easily overlooked. But we now know that low-concentration monoclonal gammopathies of undetermined significance (MGUS)2 represent disorders that will, in a significant percentage of cases, eventually become malignant diseases (1). For decades, the clinical laboratory has exploited the clonal nature of the immune response to detect myeloma and MGUS by using serum protein electrophoresis (SPE). When serum from a healthy patient undergoes electrophoretic separation, the fraction containing the patient's immunoglobulin shows a gaussian distribution, representing the products of thousands of different plasma cell clones, each with a unique electrophoretic mobility. When the serum is from a patient with multiple myeloma, however, every medical student knows that a spike appears instead of the normal diffuse pattern, because one monoclonal protein with only one electrophoretic mobility predominates. We now have new therapies for myeloma, so it is increasingly important to identify patients with MGUS as early as possible. We usually find them only by chance when astute caregivers request an SPE test in patients with vague signs and symptoms. M-components in MGUS are often easy to see. But how can we catch those really early ones that are still hiding, sometimes in plain sight? Over the past decade, we have tried several new approaches to protein electrophoresis in the hope that we can better detect small abnormal monoclonal immunoglobulins. High-resolution agarose gels (with enhanced electroendosmosis) and capillary zone electrophoresis (CZE) provide better separation of the …