How is Common Variable Immunodeficiency diagnosed?

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by low levels of antibodies and an increased susceptibility to infections. Diagnosing CVID involves a comprehensive evaluation of a patient's medical history, physical examination, laboratory tests, and immunological assessments.

Medical history: The first step in diagnosing CVID is a detailed medical history. The healthcare provider will inquire about recurrent or severe infections, particularly those involving the respiratory tract, sinuses, ears, and gastrointestinal system. They will also ask about any family history of immunodeficiency or autoimmune diseases.

Physical examination: A thorough physical examination is conducted to identify any signs or symptoms that may indicate CVID. This may include examining the lymph nodes, tonsils, spleen, and liver for abnormalities.

Laboratory tests: Several laboratory tests are performed to assess the immune system's function and identify any abnormalities. These tests may include:

• Complete blood count (CBC): This test measures the number of red and white blood cells, as well as platelets. Abnormalities in these counts may indicate an underlying immune disorder.


• Immunoglobulin levels: CVID is characterized by low levels of immunoglobulins, particularly IgG, IgA, and IgM. Blood tests are conducted to measure the levels of these antibodies.


• Vaccine response: Vaccination history and response to vaccines can provide valuable information about the immune system's ability to produce antibodies. Patients with CVID often have poor responses to vaccines.


• Autoimmune markers: Autoimmune diseases are commonly associated with CVID. Testing for autoimmune markers, such as antinuclear antibodies (ANA), can help identify any underlying autoimmune conditions.


• Complement levels: Complement proteins play a crucial role in the immune response. Testing the levels of complement proteins can help evaluate the immune system's functionality.

Immunological assessments: Additional immunological assessments may be performed to further evaluate the immune system's function. These tests may include:

• Lymphocyte subset analysis: Flow cytometry is used to measure the different types of lymphocytes, such as T cells, B cells, and natural killer (NK) cells. CVID is characterized by abnormalities in these subsets.


• Immunoglobulin subclass analysis: This test measures the levels of different subclasses of immunoglobulins (IgG1, IgG2, IgG3, IgG4). CVID patients often have imbalances in these subclasses.


• B cell phenotyping: Flow cytometry can also be used to analyze the expression of specific markers on B cells. CVID patients may exhibit abnormalities in B cell subsets.


• Genetic testing: In some cases, genetic testing may be recommended to identify specific gene mutations associated with CVID. However, genetic testing is not always necessary for diagnosis.

It is important to note that the diagnosis of CVID requires the exclusion of other potential causes of immunodeficiency. Other primary immunodeficiency disorders, secondary immunodeficiencies, and certain medications or medical conditions can mimic the symptoms of CVID. Therefore, a comprehensive evaluation is crucial to ensure an accurate diagnosis.

In conclusion, diagnosing Common Variable Immunodeficiency involves a combination of medical history assessment, physical examination, laboratory tests, and immunological assessments. These evaluations help identify the characteristic features of CVID, such as low immunoglobulin levels, poor vaccine responses, and abnormalities in lymphocyte subsets. A thorough diagnosis is essential to differentiate CVID from other immunodeficiency disorders and provide appropriate management and treatment for affected individuals.