Diagnostic Criteria and Treatment for Common Variable Immunodeficiency (CVID)

Diagnostic Criteria for CVID

The diagnosis of CVID should be considered in male or female subjects older than 4 years who have low IgG and IgA levels and impaired antibody response but do not have genetic lesions or other causes of primary or secondary antibody deficiency 1, 2
Serum IgG level less than 450-500 mg/dL is a diagnostic criterion for CVID 1
Serum IgA or IgM level less than the fifth percentile is a diagnostic criterion for CVID 1
Decreased ability to make specific antibodies to both protein and polysaccharide antigens is a diagnostic criterion for CVID 1, 3
Normal or reduced B-cell numbers in peripheral blood, with approximately 13% of patients having less than 3% B cells among peripheral blood lymphocytes, is a diagnostic criterion for CVID 3, 4

Exclude other primary causes of agammaglobulinemia, such as X-linked agammaglobulinemia and X-linked lymphoproliferative disease, to diagnose CVID 1
Document impaired production of specific antibodies in response to protein or polysaccharide antigens, which is essential for CVID diagnosis 3
Assess B-cell subsets in peripheral blood, which can correlate with clinical phenotypes and may be useful for CVID classification 4

The EUROclass classification incorporates features of the Freiburg and Paris classifications, based on total numbers of B cells and B-cell subsets, such as switched memory B cells, marginal zone B cells, transitional B cells, and CD21low cells 4
Decreased numbers of marginal zone and class-switched B cells correlate with granulomatous disease and splenomegaly in CVID patients 4
Expansion of CD21low B cells correlates with splenomegaly in CVID patients 4
Expansion of transitional B cells is associated with lymphadenopathy in CVID patients 4

Recurrent and chronic bacterial respiratory tract infections, including otitis media, sinusitis, bronchitis, and pneumonias, are common in CVID patients 1
Encapsulated bacteria, such as nontypeable H. influenzae and S. pneumoniae, and atypical bacteria, such as Mycoplasma and Ureaplasma species, are common pathogens in CVID patients 1
Recurrent and/or persistent viral respiratory tract infections, particularly rhinovirus, can occur in CVID patients 1

T-cell abnormalities are frequently found in CVID patients despite being classified as predominantly humoral immunodeficiency 4
Granulomatous disease can occur in CVID patients 4

Regular intravenous or subcutaneous immunoglobulin replacement therapy is the cornerstone of CVID treatment, with standard dosing of approximately 0.5g/kg administered every 3-4 weeks and target IgG trough levels of 8-11 g/L 5
Immunoglobulin replacement therapy significantly reduces the frequency and severity of infections in CVID patients 5

Regular monitoring of IgG trough levels is essential to ensure adequate replacement therapy in CVID patients 5
Regular monitoring of blood counts and serum chemistry can detect potential adverse effects of immunoglobulin replacement therapy in CVID patients 5

T-cell abnormalities should be evaluated when significant impairment of humoral immunity is observed in CVID patients, as they could be a component of combined immunodeficiency 3, 4