M-protein, immunofixation and serum free light chains
Myeloma cells are clones of one antibody-making cell, so they pour a single identical antibody, the M-protein, into the blood; measuring it (and the free light chains that go with it) is how myeloma is diagnosed, how deep a response is judged, and how relapse is caught before symptoms.
Overview
What is measured: the monoclonal immunoglobulin made by a plasma cell clone, and its unpaired light chains. How: serum protein electrophoresis quantifies the monoclonal peak in g/L; immunofixation identifies the heavy chain (IgG, IgA, IgM, rarely IgD or IgE) and light chain (kappa or lambda); the serum free light chain assay reports kappa, lambda and their ratio (normal 0.26 to 1.65); 24-hour urine electrophoresis and immunofixation find Bence Jones protein. Diagnostic thresholds: MGUS under 30 g/L, smouldering myeloma 30 g/L or more or urine protein of 500 mg a day without myeloma-defining events, and an involved to uninvolved free light chain ratio of 100 or more is itself a myeloma-defining event; light-chain-only myeloma is about 15 percent and non-secretory disease about 3 percent, needing marrow and imaging; Waldenström's has an IgM paraprotein and viscosity testing, AL amyloidosis is followed by free light chains, and daratumumab (an IgG kappa antibody) can mimic a small M-protein unless a shift assay is used. What a result changes: the IMWG response categories run from partial (a fall of half or more), very good partial (90 percent or more, or immunofixation-positive only), complete (negative immunofixation with under 5 percent plasma cells) to stringent complete (normal ratio, no clonal cells) and then measurable residual disease; progression is a 25 percent rise with an absolute increase of 5 g/L; values are checked every one to three months on therapy and every three to six months in remission, and a rising paraprotein triggers imaging and marrow before symptoms return. Where it matters: smouldering myeloma, transplant-eligible and ineligible myeloma, relapsed myeloma, plasma cell leukaemia, Waldenström's and marginal zone lymphoma.
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