At a Glance

Common variable immunodeficiency (CVID) should be considered in patients with recurrent bacterial otitis, pneumonia, bronchitis, sinusitis, or gastrointestinal infection with giardia. Sinopulmonary infections are usually caused by routine bacteria, such as Hemophilus, Streptococci, pneumococcus, and mycoplasma. Recurrent bronchitis and pneumonia leading to bronchiectasis also raise the suspicion that an immunodeficiency, such as CVID, may be present.

Autoimmune disease together with immunodeficiency also suggests the diagnosis. Autoimmune diseases seen with CVID include autoimmune hemolytic anemia, rheumatoid arthritis, celiac disease, inflammatory bowel disease, and others. Granulomatous infiltration of the lungs and liver can also be present.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Serum immunoglobulins (IgG, IgA, IgM, IgE) should be measured. CVID is characterized by depressed levels of at least two classes of antibodies. An elevation in IgM might suggest that the patient has one of the hyperIgM syndromes, which are another class of diseases causing low serum IgG. Isolated depression in IgA suggests the possibility of selective IgA deficiency. Elevation of IgE in a patient with recurrent infections and skin rashes might suggest hyperIgE syndrome or some other immunodeficiencies associated with elevated IgE, including ataxia telangiectasia, Wiskott-Aldrich syndrome, and DiGeorge syndrome. (Table 1)

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Table 1.
200 mg/dL 10 mg/dL 10 mg/dL

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Severe protein losing conditions, such as nephrotic syndrome, protein-losing enteropathy, or severe burns, may cause secondary decreases in gamma globulins. Also, severe protein-calorie malnutrition may be associated with low gamma globulins. The low values of immunoglobulins should be confirmed by repeat lab tests.

The age of the patient influences the expected, normal reference range. Appropriate age-adjusted reference ranges should be used to compare with the measured serum concentrations of immunoglobulins.

What Lab Results Are Absolutely Confirmatory?

In most cases, confirmatory testing is not necessary.

Mutations responsible for CVID can be identified in about 15% of patients currently. The genes involved include TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor), ICOS (inducible co-stimulator of activated T cells), and CD19 (a B-cell surface molecule). Those genes can be sequenced to establish the genetic diagnosis, but the tests are not sufficiently sensitive to rule out the diagnosis.

What Confirmatory Tests Should I Request for My Clinical Dx? In addition, what follow-up tests might be useful?

Follow-up testing should be informed to determine the IgG response to immunization with usual childhood immunization, but live-virus immunization should not be performed. Patients with CVID usually fail to respond normally to protein and carbohydrate immunization.

Flow cytometry should be performed to enumerate the B-cells and T-cells. Most patients with CVID have a normal number of circulating lymphocytes. Severe decreases in lymphocyte numbers should suggest another diagnosis, including HIV infection or a different B-cell, T-cell, or combined immunodeficiency.

What Factors, If Any, Might Affect the Confirmatory Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Use of chronic high-dose glucocorticoids can cause mildly low immunoglobulin concentrations. Use of rituximab or other immunosuppressive drugs can lead to decreased immunoglobulin levels.