Diagnosis
The diagnosis is based on a combination of clinical features together with laboratory findings, potentially a positive family history and increasingly, genetic testing. The clinical presentation for antibody deficiency is often characterised by recurrent sinopulmonary infections which often take longer to resolve requiring prolonged or intravenous antibiotic courses. In addition to the infections presentations complications may include autoimmune cytopenias, lymphoproliferation, non-infectious inflammation and allergy linked to underlying immune dysregulation. Primary antibody deficiency disorders are also linked to an increase in malignancy in particular lymphoma and gastric cancers (4,6).
Initial laboratory assessment is to determine the levels of immunoglobulins (IgG, IgA and IgM) alongside functional information on vaccine responses and lymphocyte enumeration in particular B cells (Figure 1). The commonest clinically relevant primary antibody deficiency of adults is Common variable immunodeficiency (CVID) and if diagnostic criteria (7) are fulfilled the decision to commence immunoglobulin replacement therapy (IgRT) is usually straightforward. However careful assessment and monitoring is required for both IgRT and the non-infectious complications. Genetic testing is now of key importance, to where possible define a molecular diagnosis allowing optimization and personalisation of therapy where pathway-specific approaches are indicated. An example of this is the use of abatacept in CTLA4 deficiency. There have also been major advances in the screening of newborns using TREC and KREC assays and in adults using calculated globulin (8,9)