A case of monoclonal gammopathy of renal significance presenting as atypical amyloidosis with IgA lambda paraproteinemia

Abstract

Monoclonal gammopathy of renal significance is defined as any B cell or plasma cell clonal lymphoproliferation which neither causes tumor complications nor meets any current hematological criteria for specific therapy, with one or more kidney lesions related to the produced monoclonal immunoglobulin, such as amyloidosis. A 50-year-old male presented with heavy proteinuria and blood tests showing IgA and Lambda paraproteinemia. Light microscopy showed mesangial eosinophilic ground substance extending into the capillary loops, and positive staining within the glomeruli and vessel walls for amyloid P immunohistochemistry was also noted. Immunofluorescence showed positive staining for IgA and Lambda in the mesangia and capillary loops. Electron microscopy exhibited organized fibrils measuring 4-5 nm in diameter in the mesangia, glomerular basement membranes and vessel walls. We interpreted the overall findings as atypical renal amyloidosis with IgA and Lambda deposition on immunofluorescence. Further amyloid typing using laser microdissection-liquid chromatography and mass spectrometry will be useful.

AB-Amy: machine learning aided amyloidogenic risk prediction of therapeutic antibody light chains

“…The majority of antibody-related amyloidosis is light-chain (AL) amyloidosis. In addition, heavy-chain (AH) amyloidosis and immunoglobulin heavy- and light-chain (AHL) amyloidosis are reported [ 10 , 11 ]. AL, also known as primary amyloidosis, is a type of complex and incurable disease caused by abnormal clone plasma cells overproducing immunoglobulin light chains (LCs) that misfold and aggregate as amyloidogenic fibrils in certain organs [ 12 , 13 ].…”

“…AL, also known as primary amyloidosis, is a type of complex and incurable disease caused by abnormal clone plasma cells overproducing immunoglobulin light chains (LCs) that misfold and aggregate as amyloidogenic fibrils in certain organs [ 12 , 13 ]. AL is often related to multiple myeloma [ 14 ] and often leads to cardiac amyloidosis or systemic amyloidosis that affects the kidney, peripheral and autonomic nervous system, liver and other organs [ 11 ]. As a result, the therapeutic antibody should not contain LCs with an amyloidogenic risk for the safety of patients.…”