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Common variable immunodeficiency and IgG deficiency comparison – addressing a diagnostic conundrum

Published online: December 14, 2018

Common variable immunodeficiency (CVID) is a collection of hypogammaglobulinemia syndromes which form the most prevalent symptomatic primary immunodeficiency disease (PID). This defect is defined by markedly reduced serum IgG in combination with reduced IgA and/or IgM levels, deficient to absent antibody responses to infections or immunization, and absence of other defined primary or secondary immune defects. Symptomatic hypogammaglobulinemic subjects do not always fulfill all CVID criteria, having normal IgA and IgM and/or normal vaccine responses, and fall more logically in the category of IgG deficiency. However, both CVID and IgG deficient subjects commonly come to medical attention due to recurrent sinopulmonary infections and as a general consensus, subjects with demonstrable antibody deficiency are treated with IgG replacement. In many cases however, IgG deficient patients are still given a CVID diagnosis, leading to both concern and added surveillance by other caregivers for the development of non-infectious complications and the potential morbidity associated with this diagnosis.

In a recently published article in The Journal of Allergy and Clinical Immunology: In Practice, Filion and colleagues studied large cohorts of subjects with CVID or IgG deficiency to compare the immunological markers and clinical manifestations of both groups of subjects and consequently delineate key differences. This was done by retrospective chart review of patients who had been referred to their center within a four-year period and had received diagnostic codes for either CVID or IgG deficiency. Immunological markers such as baseline immunoglobulin levels, protein and polysaccharide serological titers, and lymphocyte subpopulations; as well as clinical data including infectious and non-infectious manifestations were compiled from each group of patients and compared through statistical analysis.

In contrast to IgG deficient patients (N=124), the authors found that CVID patients (N=128) had significantly lower IgG levels, greater unresponsiveness to most vaccines, lower percentages of memory and isotype switched-memory B cells, and, surprisingly, lower CD4 T cell counts. Clinically, CVID and IgG deficient patients presented similar rates of sinusitis and pneumonias, but the former group presented a significantly higher prevalence of bronchiectasis and non-infectious complications such as autoimmune cytopenias, interstitial lung disease, granulomatous lesions, splenomegaly, and lymphoid malignancies.

Comparing clinical and immunological features of CVID and IgG deficient patients in a large cohort better differentiates these two clinical entities and allows the authors to conclude that these patient groups 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 help guide management challenges that these patients pose regarding antibioprophylaxis and IgG substitution therapy.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.