Laboratory Support for Diagnosis of Amyloidosis

Abstract

The definitive diagnosis of amyloidosis requires identification and characterization of amyloid deposits. Serum- and urine-based laboratory testing are important initial observations in guiding both the differential diagnosis of primary amyloidosis (AL) and the testing for identifying and characterizing tissue amyloid. Since the fibrils in AL are derived from intact or fragmented monoclonal immunoglobulin light chains, patients with AL typically have intact monoclonal immunoglobulin and/or free immunoglobulin light chains in their serum and/or urine. Protein electrophoresis (PEL) is the most utilized laboratory method to detect these monoclonal proteins. The fundamental principle of the test is the detection of monoclonal immunoglobulins from the polyclonal immunoglobulin background by their relatively restricted mobility. Immunofixation electrophoresis (IFE) can be used to type the monoclonal immunoglobulin. Unlike patients with multiple myeloma, AL patients may have a very small population of clonal plasma cells in the bone marrow which can elude detection by PEL and IFE. A newer, more sensitive, immunonephelometric assay is available to quantify the serum immunoglobulin free light chains (FLCs). The FLC assays have increased the diagnostic sensitivity for identification of light chain diseases such as AL, and in addition they have improved disease monitoring and prognosis. The FLC κ/λ ratio in conjunction with serum IFE defines a sensitive diagnostic screen for AL and reduces the need for urine PEL in the screening algorithm