La spettrometria di massa nella diagnosi e nel monitoraggio delle gammopatie monoclonali

AUTORI

ABSTRACT

Mass spectrometry in diagnosis and monitoring of monoclonal gammopathies

The identification ofmonoclonal components requires the use of protein electrophoresis, immunofixation electrophoresis of serum andurine and serum free light chain measurement. The combination of these three tests grants the highest diagnosticperformance in different clinical settings. In clinical practice, the monoclonal protein (M-protein) is detected in apatients’ serum or urine by the appearance of a distinct protein band migrating within regions typically occupied byimmunoglobulins. Immunofixation or immunotyping then provides evidence that the identified protein band is anintact immunoglobulin or an immunoglobulin light chain. Taking into consideration that each M-protein is composedby a sequence of amino acids pre-defined by somatic recombination unique to each clonal plasma cell, the molecularmass of the M-protein can act as a surrogate marker of the protein composition. The Mayo Clinic researchersestablished mass spectrometry-based methods to assign molecular mass to the monoclonal immunoglobulin lightchain and used this to detect the presence of M-proteins. The first method proposed is based on the enrichment ofserum for immunoglobulins, followed by reduction to separate light chains from heavy chains, followed by microflowLC-ESI-Q-TOF mass spectrometry. The second method is based on the enrichment of nanobodies and thesubsequent analysis on a matrix-assisted laser desorption mass spectrometer (MALDI). Both methods demonstrateda comparable diagnostic sensitivity to the standard procedures and could be considered as a possible futuresubstitution of immunofixation.

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