Immunology and AllergyTier 2Topic

Laboratory investigations - protein electrophoresis

Role

Serum protein electrophoresis (SPEP) separates serum proteins by size/charge into characteristic bands (albumin, alpha-1, alpha-2, beta, gamma) - the primary screening test for paraproteinaemia and can also suggest other systemic conditions
Used whenever a plasma cell disorder (myeloma, MGUS, amyloidosis) or unexplained raised total protein/immunoglobulins is being investigated

Patterns

A monoclonal band (M-spike) in the gamma (or sometimes beta) region reflects a single clonal population of plasma cells producing identical immunoglobulin - the hallmark of a plasma cell disorder
Polyclonal gammopathy (a broad-based increase across the gamma region, not a discrete spike) instead reflects a diffuse immune response - chronic infection, inflammation, or liver disease

Interpretation

A monoclonal band on SPEP is followed by immunofixation electrophoresis (identifies the specific heavy and light chain type) and serum free light chain assay (more sensitive, detects light-chain-only or oligosecretory disease that SPEP alone can miss)
Reduced albumin with a diffuse polyclonal gamma rise is the classic pattern in chronic liver disease ("beta-gamma bridging" specifically suggests cirrhosis)

Acting on the result

A monoclonal band identified on screening 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: hyperCalcaemia, Renal impairment, Anaemia, Bone lesions)

Associations

Multiple myeloma, MGUS, AL amyloidosis (light chain-derived), Waldenstrom macroglobulinaemia, chronic liver disease (polyclonal pattern)

Key point

A newly identified monoclonal band, even if small and asymptomatic, warrants at minimum a baseline workup and long-term follow-up given the lifelong risk of progression inherent to MGUS

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