The investigation of immunodeficiency can be complicated and expensive. It should only be undertaken where there is clear evidence of recurrent infection or relevant family history. Primary immunodeficiencies are very rare and are usually detected in childhood. However, they do not all result in repeated life threatening infection and can remain undetected until adult life. Investigation of immunodeficiency should only be carried out after discussion with a member of the consultant Immunology staff.

The pattern of infections provides key information for diagnosing the type of immunodeficiency:

Repeated bacterial infections, particularly with encapsulated organisms, suggest antibody or complement deficiency. Useful initial investigations are IgG, IgA and IgM levels, C3 and C4. IgG subclasses should also be measured.

Repeated viral and/or fungal infections suggest a T cell abnormality. A useful initial investigation in addition to those above is a lymphocyte count. Lymphocyte phenotyping and function tests are required to fully assess T cell immunity. These tests are available only by prior arrangement with the Immunology laboratory.

Staphylococcal skin sepsis, deep-seated fungal infections, poor wound healing and severe periodontal problems suggest a neutrophil abnormality. Neutrophil function tests and surface marker analysis are required to fully assess neutrophil activity. These tests are available only by prior arrangement with the Immunology laboratory.

Prior to any detailed analysis of leucocyte function and phenotype it is obviously important that a full blood count is obtained.

Specific protocols are used for the monitoring of acquired immunodeficiencies resulting from viral infection. These should only be applied following confirmation of HIV status. Lymphocyte phenotyping cannot be used as a surrogate marker for HIV infection.

Amongst the tests which can be carried out are:

Lymphocyte Subsets and Function Tests

Lymphocyte function tests (PHA stimulation) may be performed after consultation with the laboratory and Consultant Immunologist.

Granulocyte / Neutrophil Function

Granulocyte/neutrophil function analysis can be performed if the total granulocyte count is normal after consultation with the laboratory. Primary deficiencies are extremely rare. Always associated with recurrent deep-seated bacterial or fungal infections. Deficiencies in opsonic activity, ie failure to trigger granulocyte function due to low complement or IgG levels are more common. Primary deficiencies can be studied by phagocytosis, phenotypic or respiratory burst measurements. 

Immunoglobulin measurements

Serum immunoglobulin levels are essential in the investigation of immune deficiency. If there is strong suspicion of primary immunodeficiency further tests can be considered. Individual IgG subclasses can be deficient even if the total IgG level is within the normal range. Even if all levels are apparently normal it is possible that the patient is not producing functional antibody. Measurement of antibodies to Tetanus Toxoid; Haemophilus Influenzae and to Pneumococcal Polysaccharide will give a further indication of the immune status. These assays will only undertaken following prior discussion with the laboratory. 

Complement measurements

Complement deficiency is investigated by use of Haemolytic assays for the Classical Pathway and Alternative Pathway. If deficiency in either pathway is detected the laboratory will carry out further tests to determine which component is lacking. These tests are only available after prior consultation with the laboratory. It is essential that serum samples reach the laboratory within one hour of collection.

C1 inhibitor deficiency (antigenic or functional) is transmitted as an autosomal dominant disorder resulting in Hereditary Angioneurotic oedema. Acquired C1 inhibitor deficiency may occur with B-cell lymphomas. Samples collected during an acute attack of angioedema due to C1 inhibitor deficiency are characterised by a low C4.


Lymphocyte subset estimations are performed using monoclonal antibodies to: CD3, CD4 and CD8 on whole blood (sodium EDTA sample).

The percentages and absolute numbers of the lymphocyte subsets are evaluated using a Flow Cytometer.

The results are reported as percentages and absolute counts (cells/uL).

A cumulative result report is produced to show the trend in absolute CD4 counts, the ratio of CD4:CD8 and the total lymphocyte count.

Normal adult CD4 count should be >0.5 cells/uL.

NB A low CD4 count is not diagnostic of HIV infection and should always be repeated when immunodeficiency is suspected as acute infections can decrease the numbers of circulating CD4 lymphocytes.

Page updated: 22/09/14 | Updated by: Anna McHugh

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