Diagnostic accuracy of monoclonal antibody based serum immunoglobulin free light chain immunoassays in myeloma cast nephropathy

Colin A Hutchison,Mark Cook,Paul Cockwell

doi:10.1186/1472-6890-12-12

Abstract

BackgroundThe development of serum immunoassays for the measurement of immunoglobulin free light chains has led to a paradigm shift in the diagnosis, assessment and monitoring of patients with plasma cell dyscrasias. The impact of these immunoassays which employ polyclonal antibodies was most notable for those patients who were previously classified as non-secretory multiple myeloma. Recently new monoclonal antibody based assays have become available. The purpose of this study was to compare the diagnostic sensitivity of these new assays with those already in clinical practice.MethodsSera from 30 patients who present with severe acute kidney injury and multiple myeloma were identified for analysis. A head to head comparison of the two commercially available free light chains assays was then undertaken to determine if their diagnostic sensitivity and specificity were comparable.ResultsIn this first assessment of the utility of these new assays, we found that one of 17 patients with a lambda monoclonal free light chain resulting in acute kidney injury were not identified and a further 12% of patients were wrongly classified as having levels below those associated with disease specific acute kidney injury.ConclusionThese results suggest that caution should be applied to the use of new free light chain assays in the assessment of patients with a monoclonal gammopathy.

Highlights

The development of serum immunoassays for the measurement of immunoglobulin free light chains has led to a paradigm shift in the diagnosis, assessment and monitoring of patients with plasma cell dyscrasias
The development of polyclonal nephelometric immunoassays for the measurement of free immunoglobulin light chains (FLC) in the serum has changed screening algorithms, classifications and the monitoring of a number of plasma cell dyscrasias [1,2,3]. These assays, which utilise latex-conjugated polyclonal antisera, when combined with serum protein electrophoresis provide a sensitive screening tool for plasma cell dyscrasias. Together they identify all cases of multiple myeloma, 96% of ALamyloidosis and 85% of monoclonal gammopathy of undetermined significance (MGUS) [4]
Sera from 30 patients with severe acute kidney injury (AKI) and multiple myeloma were available for analysis

Summary

Introduction

The development of serum immunoassays for the measurement of immunoglobulin free light chains has led to a paradigm shift in the diagnosis, assessment and monitoring of patients with plasma cell dyscrasias. The development of polyclonal nephelometric immunoassays for the measurement of free immunoglobulin light chains (FLC) in the serum has changed screening algorithms, classifications and the monitoring of a number of plasma cell dyscrasias [1,2,3] These assays, which utilise latex-conjugated polyclonal antisera, when combined with serum protein electrophoresis provide a sensitive screening tool for plasma cell dyscrasias. Together they identify all cases of multiple myeloma, 96% of ALamyloidosis and 85% of monoclonal gammopathy of undetermined significance (MGUS) [4]. Recent work has demonstrated that when treatments are targeted to provide a rapid reduction in circulating concentrations of monoclonal FLC renal recovery occurs in the majority of patients [12,13,14,15]

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