Serum or urine electrophoresis, immunofixation, and free light chain assays

Role

Serum/urine protein electrophoresis and immunofixation identify and characterise monoclonal proteins (paraproteins) - central to diagnosing and monitoring plasma cell disorders (MGUS, multiple myeloma, AL amyloidosis, Waldenstrom macroglobulinaemia)
Performed whenever a plasma cell disorder is suspected (unexplained anaemia, renal impairment, bone pain/lytic lesions, hypercalcaemia) or as part of AL amyloidosis workup

Serum protein electrophoresis (SPEP) separates proteins by charge/size, identifying a monoclonal band (M-spike) if present; immunofixation electrophoresis then identifies the specific heavy and light chain type (e.g. IgG kappa) of the monoclonal protein, providing more specific characterisation than SPEP alone

Serum free light chain assay is more sensitive than electrophoresis and can detect light-chain-only or oligosecretory disease that SPEP/immunofixation might miss - particularly important in AL amyloidosis, where light chain-only secretion is common
Urine electrophoresis/immunofixation specifically detects Bence Jones protein (free light chains in urine) - not reliably detected by standard urine dipstick (which primarily detects albumin), a frequently tested distinction
The combination of serum electrophoresis/immunofixation + serum free light chains is now considered adequate for excluding most plasma cell disorders, with 24-hour urine electrophoresis reserved for specific circumstances given serum free light chains' high sensitivity

A confirmed monoclonal band triggers workup to distinguish MGUS (small band, no end-organ damage, low progression risk, monitored) from multiple myeloma (larger band with end-organ damage - the CRAB criteria) or other plasma cell disorders
Serial monitoring of paraprotein level and free light chain ratio tracks disease activity and treatment response in confirmed myeloma/related disorders

Multiple myeloma, MGUS, AL amyloidosis, Waldenstrom macroglobulinaemia (IgM paraprotein), Bence Jones proteinuria and myeloma cast nephropathy

Standard urine dipstick does not reliably detect Bence Jones protein (free light chains) - a key trap in suspected myeloma workup, where specific urine electrophoresis/immunofixation (or, more practically now, serum free light chain assay) is required rather than relying on a negative dipstick to exclude significant proteinuria

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