Polyclonal and oligoclonal hypergammaglobulinemia

Last updated Nov. 1, 2025, 10:23 p.m. by ivo

Tags: Hypergammaglobulinemia

Hypergammaglobulinemia results from an overproduction of immunoglobulins. This process may be polyclonal or oligoclonal (i.e. increased synthesis from multiple plasma cell lines as seen in infection); or monoclonal (increased synthesis from a single plasma cell clone).

A monoclonal gammopathy may be related to a plasma cell dyscrasia such as multiple myeloma, Waldenstrom’s macroglobulinaemia or a monoclonal gammopathy of undetermined significance (MGUS). A polyclonal increase in gamma globulins is a non-neoplastic phenomenon that is indicative of diffuse activation of B cells and is a sign of inflammation.

Causes of polyclonal hypergammaglobulinemia

• Liver disease
• Autoimmune and connective tissue disease, e.g. RA, SLE, Sjogren’s
• Infections
• Malignancy

Myeloma or Waldenstrom’s macroglobulinaemia usually present with a monoclonal paraprotein detectable on serum electrophoretic and immunofixation studies. Myeloma sometimes only has monoclonal light chains detectable on serum free light chain or urine Bence-Jones protein analysis.

A finding of increased polyclonal gammaglobulins is not indicative of a plasma cell dyscrasia and does not require a review by a haematologist

Further evaluation

• Due to the broad differential diagnosis, a thorough clinical assessment is required to exclude the above conditions.
• Follow up FBC, full ELFTs (including corrected calcium), serum protein electrophoresis and serum free light chain testing in 6 months is recommended to confirm stability or resolution of the raised gamma globulins.

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