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)