Immunoglobulin levels are essential only in investigations for immunodeficiency states and in suspected myeloma or related lymphoid malignancies where they should be carried out in conjunction with serum electrophoresis. Elevated levels of immunoglobulins may be of limited use in the differential diagnosis of some diseases e.g chronic liver disease where primary biliary cirrhosis is characterised by raised IgM: IgG and IgA are raised in viral hepatitis, IgA in portal cirrhosis. Immunoglobulin measurements are a poor indicator of general inflammation. In fact, immunoglobulin determinations are in general overrequested, misused and misunderstood.

Immunodeficiency
Patients with infections, particularly bacterial infections, that are Severe, Prolonged, Unusual or Recurrent (SPUR) without known cause should be investigated for immunoglobulin deficiency. Hereditary immunoglobulin deficiencies are generally rather rare. IgG deficiencies are usually associated with infections of this type. IgM deficiency is very uncommon. IgA deficiency is the commonest of the immunoglobulin deficiencies. The incidence is 1 in 500 of the general population, most of whom have no symptoms of increased infectious disease. The most common associations of IgA deficiency are with autoimmune disease particularly coeliac disease. Acquired immunoglobulin deficiencies are more common usually resulting from protein losing disorders or haematological malignancy but also as consequences of malnutrition, some viral infections and some drug regimes.

Hereditary IgG deficiency is usually symptomatic though the symptoms (often bronchiectasis) may not be identified until later in life. It is unfortunately the case that despite onbviuos symptoms, IgG deficiencies often go undetected for up tom 10m or more years. Most deficiencies affect all of the four IgG subclasses. However, isolated deficiencies of each of the four subclasses have been recognised. These may or may not be symptomatic. Functional immunoglobulin deficiencies can also be found.

The commonest presentations of IgG deficiency are (in order) recurrent chest, sinus or gut infections.

Lymphoid malignancy
Samples sent for immunoglobulin (IgG,IgA,IgM) measurements are also investigated by electrophoresis even if this is not requested. Electrophoresis is essential in the investigation of suspected paraproteinaemia. A paraprotein will give a characteristic band (M protein monoclonal band) depending on the immunoglobulin type and its concentration.

In any serum where a paraprotein is detected for the first time or if the paraprotein pattern changes, the nature of the paraprotein will be determined by immunofixation. This may identify not only IgG, IgA or IgM paraproteins but also the very rare IgD or IgE paraproteins. Free light chain paraproteins may also be detected. Bence Jones proteins are immunoglobulin light chains found in urine or some patients with myeloma or other lymphoid malignancies All patients with these diseases should be investigated for Bence Jones proteins since there are situations where myeloma including light chain myelomas could be missed on serum electrophoresis.

The presence of significant amounts of Bence Jones Proteinuria are indicative of malignant B cell proliferation. Small amounts (< 0.05 g/L) may occur with benign B cell proliferation. It is important to look at both blood and urine in the investigation of myeloma. The marked variability in the excretion of BJP makes this test unreliable for monitoring myeloma. Newer assays for the detection of serum free light chains may be of value in such situations

Characteristic electrophoretic patterns are also seen in the presence of an acute phase response, immunodeficiency, nephrotic syndrome, α1 antitrypsin deficiency, inflammatory and infective disorders. Although the laboratory will report such findings, electrophoresis is seldom of value as a diagnostic or prognostic indicator in these diseases.