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Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency

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Abstract

Purpose

Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older).

Methods

Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups.

Results

After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients.

Conclusions

These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for continued longitudinal study of pediatric and early-onset CVID patients to further characterize accrual of features over time.

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Abbreviations

CLABSI:

Central line associated bloodstream infection

CVID:

Common variable immunodeficiency

ESID:

European Society for Immunodeficiencies

USIDNET:

United States immune deficiency network

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Acknowledgments

The authors gratefully acknowledge the patients, physicians, nurses, and study coordinators who made this possible. USIDNET Consortium members contributing to this study include Javeed Akhter, Andrea Apter, Zuhair Ballas, Mark Ballow, Jeffrey Bennion, Francisco Bonilla, Rebecca Buckley, Leonard Calabrese, Jose Calderon, Jason Caldwell, Karin Chen, Laurence Cheng, Jim Fernandez, Ramsay Fuleihan, Ivan Fuss, Christopher George, Gabriel Gonzalez, Richard Guillot, Katherine Gundling, Elie Haddad, Vivian Hernandez-Trujillo, Robert Hostoffer, Avni Joshi, Charles Kirkpatrick, Gary Kleiner, Adina Knight, Roger Kobayashi, Heather Lehman, David Lowe, Mica Muskat, Luigi Notarangelo, Hans Ochs, Terry Overby, Niraj Patel, Jennifer Puck, Robert Rabinowitz, John Routes, Elizabeth Secord, Ralph Shapiro, Mark Stein, Warren Strober, Daniel Suez, Bobo Tanner, Martha White, Dowain Wright, Grace Yu. The authors gratefully acknowledge the assistance of the USIDNET staff Tara Caulder and Marla Goldsmith.

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Authors and Affiliations

  1. Division of Allergy and Immunology, Children’s Hospital of Philadelphia, ARC 1216, 3615 Civic Center Blvd., Philadelphia, PA, 19104, USA

    Lauren A. Sanchez, Solrun Melkorka Maggadottir & Kathleen E. Sullivan

  2. Department of Pediatrics, University of California, San Francisco, San Francisco, CA, 94143, USA

    Matthew S. Pantell

  3. Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, NC, 27708, USA

    Patricia Lugar

  4. Division of Allergy and Immunology, Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Charlotte Cunningham Rundles

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  1. Lauren A. Sanchez
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  2. Solrun Melkorka Maggadottir
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  3. Matthew S. Pantell
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  4. Patricia Lugar
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  5. Charlotte Cunningham Rundles
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  6. Kathleen E. Sullivan
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the USIDNET Consortium

Corresponding author

Correspondence to Kathleen E. Sullivan.

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Funding Sources

Supported in part by NIH U24AI086037 and the Wallace Chair of Pediatrics (KES). The authors gratefully acknowledge the support of USIDNET by Baxalta and the Immune Deficiency Foundation.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Sanchez, L.A., Maggadottir, S.M., Pantell, M.S. et al. Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency. J Clin Immunol 37, 592–602 (2017). https://doi.org/10.1007/s10875-017-0415-5

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  • DOI: https://doi.org/10.1007/s10875-017-0415-5

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