2019Laboratory MedicineOpen access

Serum Free Light Chain Assay in Monoclonal Gammopathic Manifestations

Won S. Lee, Gurmukh Singh

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Abstract

BACKGROUND: Serum free light chain assay is used in the diagnosis and monitoring of monoclonal gammopathic manifestations. For the kappa (κ)/lambda (λ) ratio, there is a 36% false-positive rate in patients without monoclonal gammopathic manifestations and a 30% false-negative rate in patients with monoclonal gammopathic manifestations. This study was undertaken to address the higher false-negative rate in λ chain-associated monoclonal lesions. METHODS: Results of serum protein electrophoresis, serum immunofixation electrophoresis, and serum free light chain assays were reviewed retrospectively. The results for serum free light chains in cases of intact immunoglobulin monoclonal gammopathic manifestations only were analyzed. RESULTS: Concentrations of involved serum free light chains were significantly higher in κ chain-associated lesions than in λ chain-associated lesions. The concentration of uninvolved light chains was significantly higher in λ chain-associated lesions. CONCLUSIONS: κ light chains are present in significantly greater abundance than are λ chains in their respective monoclonal lesions. Moreover, κ and λ light-chain levels are not comparable for similar quantitative levels of monoclonal immunoglobulins. The findings warrant a reconsideration of the role of serum free light chain concentrations and involved to uninvolved serum free light chain ratio in designation of myeloma-defining conditions and other diagnostic criteria based on serum free light chain assay.

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BACKGROUND: Serum free light chain assay is used in the diagnosis and monitoring of monoclonal gammopathic manifestations. For the kappa (κ)/lambda (λ) ratio, there is a 36% false-positive rate in patients without monoclonal gammopathic manifestations and a 30% false-negative rate in patients with monoclonal gammopathic manifestations. This study was undertaken to address the higher false-negative rate in λ chain-associated monoclonal lesions. METHODS: Results of serum protein electrophoresis, serum immunofixation electrophoresis, and serum free light chain assays were reviewed retrospectively. The results for serum free light chains in cases of intact immunoglobulin monoclonal gammopathic manifestations only were analyzed. RESULTS: Concentrations of involved serum free light chains were significantly higher in κ chain-associated lesions than in λ chain-associated lesions. The concentration of uninvolved light chains was significantly higher in λ chain-associated lesions. CONCLUSIONS: κ light chains are present in significantly greater abundance than are λ chains in their respective monoclonal lesions. Moreover, κ and λ light-chain levels are not comparable for similar quantitative levels of monoclonal immunoglobulins. The findings warrant a reconsideration of the role of serum free light chain concentrations and involved to uninvolved serum free light chain ratio in designation of myeloma-defining conditions and other diagnostic criteria based on serum free light chain assay.

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Available abstract

BACKGROUND: Serum free light chain assay is used in the diagnosis and monitoring of monoclonal gammopathic manifestations. For the kappa (κ)/lambda (λ) ratio, there is a 36% false-positive rate in patients without monoclonal gammopathic manifestations and a 30% false-negative rate in patients with monoclonal gammopathic manifestations. This study was undertaken to address the higher false-negative rate in λ chain-associated monoclonal lesions. METHODS: Results of serum protein electrophoresis, serum immunofixation electrophoresis, and serum free light chain assays were reviewed retrospectively. The results for serum free light chains in cases of intact immunoglobulin monoclonal gammopathic manifestations only were analyzed. RESULTS: Concentrations of involved serum free light chains were significantly higher in κ chain-associated lesions than in λ chain-associated lesions. The concentration of uninvolved light chains was significantly higher in λ chain-associated lesions. CONCLUSIONS: κ light chains are present in significantly greater abundance than are λ chains in their respective monoclonal lesions. Moreover, κ and λ light-chain levels are not comparable for similar quantitative levels of monoclonal immunoglobulins. The findings warrant a reconsideration of the role of serum free light chain concentrations and involved to uninvolved serum free light chain ratio in designation of myeloma-defining conditions and other diagnostic criteria based on serum free light chain assay.

Key concepts: Immunoglobulin light chain, Monoclonal, Immunofixation, Monoclonal antibody, Serum protein electrophoresis, Multiple myeloma, Molecular biology, Chemistry

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