Description
Measurement of immunoglobulins (IgG, IgA and IgM) s a commonly requested investigation in both clinical biochemistry and immunology laboratories. Whilst abnormal concentrations of these proteins are found in many conditions, only in the investigation of immune deficiency and B cell malignancy is there clear clinical justification for their measurement. Methods used for immunoglobulin measurements should be accurate, sensitive and precise. It is recommended that a protein electrophoretic separation shouldalso be done as part of the investigation of immunoglobulins as this is the only reliable way of assessing the clonality of the immunoglobulins and so detecting paraproteins. Paraproteins are the earliest described tumour markers and remain an essential part of the investigation, diagnosis and monitoring of patients with B cell dyscrasias. Electrophoresis methods should be optimised so the protein is not too heavily applied to the support medium and to enable good separation of the various zones (particularly within the beta-gamma region). Automated gel electrophoresis methods and automated capillary zone electrophoresis are now becoming available.
Samples showing paraproteins or samples with raised IgA and IgM concentrations that cannot be confirmed as polyclonal by the electrophoresis pattern, should be investigated by immunofixation to confirm or exclude the presence of a paraprotein. Immunofixation remains the method of choice for paraprotein typing because it is fast, specific, flexible and easy to interpret. Immunofixation is more sensitive than electrophoresis and may detect paraprotein bands that are not visible on routine electrophoresis.
In the laboratory investigation of B cell malignancy, both serum and urine investigations are essential. Monoclonal free light chain, Bence Jones protein, in urine is suggestive of B cell malignancy and may be the only tumour marker present. A trace of albumin should be visible in the electrophoretic separation of the urine sample to indicate adequate sensitivity.
Immunochemical quantification of paraproteins (in both serum and urine) is unreliable. The recommended method of is densitometric estimation from the protein separation and calculation of the paraprotein concentration relative to the serum or urine total protein or (in certain situations) to the globulin concentration i.e. total protein minus albumin concentration.
The measurement of serum immunoglobulin concentrations is readily available but with budgets that seem to increase more slowly than the workload, we must assess whether we are doing the tests to the best of our abilities and whether all the requests are justified.

