Serum free light chain assays not total light chain assays are the standard of care to assess Monoclonal Gammopathies

Abstract

The diagnosis of Multiple Myeloma is a challenge to the physician due to the non-specific symptoms (anemia, bone pain and recurrent infections) that are commonplace in the elderly population. However, early diagnosis is associated with less severe disease, including fewer patients presenting with acute renal injury, pathological fractures and severe anemia. Since 2006, the serum free light chain test Freelite® has been included alongside standard laboratory tests (serum and urine protein electrophoresis, and serum and urine immunofixation) as an aid in the identification of monoclonal proteins, which are a cornerstone for the diagnosis of Multiple Myeloma. The serum free light chain assay recognizes the light chain component of the immunoglobulin in its free form with high sensitivity. Other assays that measure light chains in the free and intact immunoglobulin forms are sensitive, but unfortunately, due to the nomenclature used, these assays (total light chains) are sometimes used in place of the free light chain assay. This paper reviews the available literature comparing the two assays and tries to clarify hypothetical limitations of the total assay to detect Multiple Myeloma. Furthermore, we elaborate on our study comparing the two assays used in 11 Light Chain Multiple Myeloma patients at presentation and 103 patients taken through the course of their disease. The aim of this article is to provide a clear discrimination between the two assays and to provide information to physicians and laboratory technicians so that they can utilize the International Myeloma Working Group guidelines.

The difference of free light chains as a predictor of kidney damage in patients with Multiple Myeloma

“…However, if in the literature there are more and more data relating to the clinical impact of the value of the individual FLCs and their ratio [34,35], to date, not much data has been produced about dFLC parameter, especially in relation to the kidney damage in MM patients.…”

Comparison of Serum Immunoglobulin Free Light Chains Assay and Serum Immunofixation Electrophoresis in Patient Transplanted for Multiple Myeloma

“…Nevertheless, various authors [6-8] evoke a certain interest for this assay not for the diagnosis of IIMM, but rather in monitoring the evolution of this pathology after transplant and/or chemotherapy [2]. In fact, the κ/λ ratio represents a more sensitive marker of residual disease than protein electrophoresis and serum sIFE [6,9,10]. According to Mead, et al [9] the sFLC assay can be used as a rapid indicator of treatment response in the majority of patients with MM, sFLC having 2 to 6 hours half-life compared to intact immunoglobulin (1-3 weeks).…”

Cadenas ligeras libres en suero en el diagnóstico de Gammapatías Monoclonales

“…Debido a su bajo peso molecular (25-50 kDa aproximadamente) las cadenas livianas se filtran fácilmente por el glomérulo para luego ser inmediatamente reabsorbidas en el túbulo contorneado proximal, lo que hace que su vida media en suero sea muy breve, de dos a seis horas, teniendo en cuenta que la producción fisiológica de cadenas livianas libres es de aproximadamente 0,5 g por día y que el riñón humano es capaz de reabsorber hasta 30 g/día de proteínas pequeñas, en condiciones normales. La mayoría de estas proteínas serán metabolizadas y solo pequeñas cantidades se encontrarán en orina, únicamente cuando los mecanismos de reabsorción renal se vean superados por una masiva producción, las cadenas livianas libres podrán ser detectadas por métodos electroforéticos tradicionales en una muestra de orina concentrada ya que la sensibilidad de este método es limitada debido a la reabsorción de las FLC en los túbulos renales, lo que significa que estas pueden no alcanzar un nivel detectable en orina solo hasta que se produzca la pérdida de la función tubular (4,18,33,(39)(40).…”