Abstract
IntroductionNeoplastic monoclonal gammopathies are frequently associated with production of excess free monoclonal light chains. A sensitive method for detecting free monoclonal light chains in serum could provide a marker for residual/minimal residual disease and as an adjunct to serum protein electrophoresis to serve as a screening method for monoclonal gammopathies. MethodsConventional serum immunofixation electrophoresis was modified by applying undiluted serum samples, and staining for serum free light chains with antisera specific to free light chains. Washing/blotting of gels was enhanced to remove residual proteins that did not bind to the antibodies including intact monoclonal immunoglobulins. Results from this modified immunofixation electrophoresis were compared with results from commercially available MASS-FIX/MALDI assay. ResultsMonoclonal free kappa light chains could be detected to a concentration of about 1.78 mg/L and monoclonal free lambda light chains to a concentration of about 1.15 mg/L without the need for special equipment. Comparison of these thresholds with parallel results from a commercially available MASS-FIX/MALDI assay revealed the modified electrophoretic method to be more sensitive in the context of free monoclonal light chains. ConclusionsModified serum immunofixation electrophoresis has been shown to detect low levels of monoclonal free light chains at a sensitivity suitable for the method to be used in detecting minimal residual disease, and potentially in a screening assay for monoclonal gammopathies. The disparity in the results with commercially available MASS-FIX/MALDI assay is postulated to be due to limited repertoire of reactivity of nanobodies of camelid origin.
Highlights
Neoplastic monoclonal gammopathies are frequently associated with production of excess free monoclonal light chains
MASS-FIX/MALDI did not detect monoclonal light chains at serum free monoclonal light chains (SFLC) concentration of 9.56 mg/L, the highest concentration tested in this patient
Mass Spectrometric analysis following nanobody mediated concentration of immunoglob ulins (MASS-FIX/MALDI) has been described as a method for improved sensitivity and detection of minimal residual disease (MRD), though the results of MASS-FIX/MALDI were not compared with a reference methods or gas chromatography mass-spectrometry, or even urine examina tion
Summary
Neoplastic monoclonal gammopathies are frequently associated with production of excess free monoclonal light chains. A sensitive method for detecting free monoclonal light chains in serum could provide a marker for residual/minimal residual disease and as an adjunct to serum protein electrophoresis to serve as a screening method for monoclonal gammopathies. Washing/blotting of gels was enhanced to remove residual proteins that did not bind to the antibodies including intact monoclonal immunoglobulins Results from this modified immunofixation electrophoresis were compared with results from commercially available MASSFIX/MALDI assay. Conclusions: Modified serum immunofixation electrophoresis has been shown to detect low levels of monoclonal free light chains at a sensitivity suitable for the method to be used in detecting minimal residual disease, and potentially in a screening assay for monoclonal gammopathies. The diagnostic criteria for these entities are well described and generally accepted [4] Of these only the malignant entity, MM, is treated in routine clinical care with antineoplastic drugs. The plasma cell labelling index (PCLI) may predict time to disease progression and death though currently PCLI is rarely used because of the avail ability of more practical prognostic methods [12]
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