Differentiation of Common Variable Immunodeficiency From IgG Deficiency

Abstract

Background: Common variable immunodeficiency (CVID) and IgG deficiency are 2 of the more prevalent primary humoral immune defects. The former is defined by consensus with criteria for quantitative and qualitative antibody defects, whereas the latter is used to describe patients with reduced IgG, who commonly have recurrent sinopulmonary infections but do not fulfill CVID criteria. However, these patients are often given this diagnosis.

Objective: To compare immunologic findings and clinical manifestations of 2 large cohorts of patients with CVID or IgG deficiency to better delineate differences between these syndromes.

Methods: We extracted clinical and laboratory data from electronic medical records of patients at our institution who had received International Classification of Disease codes for either CVID, or IgG deficiency. We gathered immunoglobulin levels, lymphocyte subpopulation counts, and serological vaccine responses. In some patients, we performed flow cytometry to determine percentages of memory and switched-memory B cells. We compiled and statistically compared clinical data related to infectious manifestations, bronchiectasis, autoimmune diseases, infiltrative inflammatory processes, and lymphoid malignancies.

Results: In contrast to IgG-deficient patients, we found that patients with CVID had lower IgG levels, greater unresponsiveness to most vaccines, lower percentages of memory and isotype switched-memory B cells, and lower CD4 T-cell counts. Clinically, patients with CVID presented similar rates of sinusitis and pneumonias, but a significantly higher prevalence of bronchiectasis and especially noninfectious complications.

Conclusions: CVID and IgG deficiency do not share the same disease spectrum, the former being associated with immunodysregulative manifestations and markers of a more severe immune defect. These data may allow clinicians to distinguish these conditions and the management differences that these patients pose.

Keywords: B-cell phenotyping; Cohort study; Common variable immunodeficiency; IgG deficiency; Primary immunodeficiency.

Figure 1.

Means of immunoglobulin levels in CVID and IgG deficient patients. IgG, IgA and IgM were all statistically lower in CVID patients.

Figure 2.

Protein/conjugate vaccine serologies for CVID and IgG deficient patients. (A) Percentages of protective titers in each group of patients. CVID patients were significantly less protected against Haemophilus influenzae type B, measles, mumps, tetanus, diphtheria and varicella. (B) Sum of protective and unprotective titers in each group. CVID patients had lower numbers of protective titers (among those tested) than IgG deficient patients.

Figure 3.

Pneumococcal titers post PPV23 vaccination. CVID patients had protective titers against fewer pneumococcal serotypes after PPV23 vaccination than IgG deficient patients.

Figure 4.

B cell populations in CVID and IgG deficient patients. (A) Memory B cells and switched memory B cells expressed as percentages of total B cells. CVID patients had significantly lower percentages of memory and switched memory B cells compared to IgG deficient patients and normal controls. IgG deficient patients had similar percentages of memory B cell but lower switched-memory B cells compared to normal controls. (B) B cells populations and subpopulations (absolute counts). Similar deficiencies were demonstrated when comparing absolute cell counts.

Figure 5.

T cell counts. CVID patients had significantly fewer helper T cells and more CD8 T cells than IgG deficient patients.

Figure 6.

Clinical characteristics. CVID patients had a significantly higher prevalence of bronchiectasis, autoimmunity (all types of manifestations), autoimmune cytopenias, interstitial lung disease, granulomas, splenomegaly, bronchiectasis, and non-infectious complications (of all causes).