Paraprotein (Monoclonal Gammopathy)

What is a Paraprotein?

Paraproteins (or monoclonal proteins) are abnormal immunoglobulins produced by a single clone of plasma or lymphoid cells. They are detected by serum protein electrophoresis (SPE).

They may be benign (e.g. MGUS), premalignant, or malignant (e.g. myeloma, lymphoma).

Common Types and Associations

  • IgG: Most common. Seen in MGUS and myeloma. Often indolent.
  • IgA: More likely to cause renal/bone complications. Can present with more aggressive disease.
  • IgM: Suggestive of Waldenström’s macroglobulinaemia or other lymphoproliferative disorder. May cause hyperviscosity.
  • Light chains only (kappa or lambda): Seen in light-chain myeloma or AL amyloidosis. Cannot be detected on SPE need SFLC and urine Bence-Jones testing.

Initial Tests to Request (if available)

  • FBC, U&E, calcium, albumin, LFTs
  • Serum protein electrophoresis (SPE) and immunofixation
  • Serum free light chains (SFLC) + kappa/lambda ratio
  • Urine Bence-Jones protein (early morning sample)

Stepwise Clinical Interpretation

Step 1: Quantify the paraprotein

  • <10 g/L: Usually MGUS if asymptomatic
  • 10-30 g/L: May be MGUS, smouldering myeloma, or early myeloma
  • >30 g/L: Suspicious for myeloma – refer urgently

Step 2: Likely MGUS (Monoclonal Gammopathy of Undetermined Significance)

  • Paraprotein <30 g/L
  • Normal renal function, calcium, and FBC
  • No symptoms (no bone pain, fatigue, weight loss)
  • Normal SFLC ratio

Action: Refer to haematology for baseline. Monitor annually in primary care if confirmed as MGUS.

Step 3: Suspect Myeloma (Red Flags)

  • Bone pain or pathological fractures
  • Fatigue, anaemia
  • Hypercalcaemia, renal impairment
  • Paraprotein ≥30 g/L or abnormal SFLC ratio

Action: Urgent 2WW referral to haematology with full myeloma screen (FBC, U&E, calcium, SFLC, SPE, UPE).

Step 4: IgM paraprotein or atypical findings

If IgM detected or if hyperviscosity symptoms (e.g. headaches, blurred vision, bleeding) or neuropathy:

  • Consider Waldenström’s macroglobulinaemia
  • Refer urgently to haematology

Step 5: Light Chain Only Paraprotein

  • SPE may be negative, check SFLC and urine Bence-Jones protein
  • Consider AL amyloidosis if: unexplained nephrotic-range proteinuria, hepatomegaly, restrictive cardiomyopathy

Refer to haematology urgently if suspected

Do Not Miss

  • Small paraproteins can still indicate serious disease
  • MGUS can progress (1% risk per year) → needs ongoing monitoring
  • Always check for CRAB features: Calcium ↑, Renal failure, Anaemia, Bone lesions
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