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Factors Beyond Lack of Antibody Govern Pulmonary Complications in Primary Antibody Deficiency

Journal of Clinical Immunology volume 39, pages 440–447 (2019)Cite this article

Abstract

Purpose

Pulmonary complications occur frequently in primary antibody deficiency (PAD). While the impact of antibody deficiency may appear implicit for certain respiratory infections, immunoglobulin replacement therapy does not completely ameliorate pulmonary complications in PAD. Thus, there may be antibody-independent factors influencing susceptibility to respiratory disease in PAD, but these remain incompletely defined.

Methods

We harnessed the multicenter US Immunodeficiency Network primary immunodeficiency registry to compare prevalence of asthma, bronchiectasis, interstitial lung disease (ILD), and respiratory infections between two forms of PAD: common variable immunodeficiency (CVID) and x-linked agammaglobulinemia (XLA). We also defined the clinical and immunological characteristics associated with ILD and asthma in CVID.

Results

Asthma, bronchiectasis, ILD, pneumonia, and upper respiratory infections were more prevalent in CVID than XLA. ILD was associated with autoimmunity, bronchiectasis, and pneumonia as well as fewer B and T cells in CVID. Asthma was the most common chronic pulmonary complication and associated with lower IgA and IgM in CVID. Age of symptom onset or CVID diagnosis was unrelated with ILD or asthma.

Conclusion

Despite having less severe immunoglobulin deficiency than XLA, respiratory infections, ILD, and asthma were more common in CVID. Among CVID patients, ILD was associated with autoimmunity and reduced lymphocytes and asthma with lower immunoglobulins. Though our results are tempered by registry limitations, they provide evidence that factors beyond lack of antibody promote pulmonary complications in PAD. Efforts to understand how genetic etiology, nature of concurrent T cell deficiency, and propensity for autoimmunity shape pulmonary disease may improve treatment of PAD.

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Fig. 1

Abbreviations

FB:

Follicular bronchiolitis

Ig:

Immunoglobulin

CVID:

Common variable immunodeficiency

ILD:

Interstitial lung disease

LIP:

Lymphocytic interstitial pneumonia

PAD:

Primary antibody deficiency

USIDNET:

US Immunodeficiency Network

XLA:

X-linked agammaglobulinemia

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Acknowledgements

The authors thank Tara Caulder, the USIDNET program director, and Marla Goldsmith, the registry manager, for assistance with this project as well as all physicians who enrolled patients for their contributions to USIDNET.

Funding

This work was supported by National Institutes of Health grant AI137183 (to P.J.M.).

Author information

Affiliations

  1. Department of Medicine, Center for Allergy, Asthma, and Immune Disorders, Hackensack University Medical Center, Hackensack, NJ, USA

    Tamar Weinberger

  2. Department of Pediatrics, Division of Allergy and Immunology, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Ramsay Fuleihan

  3. Department of Medicine, Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Charlotte Cunningham-Rundles & Paul J. Maglione

  4. Department of Medicine, Section of Pulmonary, Allergy, Sleep & Critical Care Medicine, School of Medicine, Boston University, Boston, MA, USA

    Paul J. Maglione

  5. Pulmonary Center, School of Medicine, Boston University, 72 East Concord Street, R304, Boston, MA, 02118, USA

    Paul J. Maglione

Authors
  1. Tamar Weinberger
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  2. Ramsay Fuleihan
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  3. Charlotte Cunningham-Rundles
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  4. Paul J. Maglione
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Contributions

T.W. performed research, analyzed and discussed data, prepared the figures, and wrote the manuscript. P.J.M. conceived the project, analyzed and discussed data, and wrote the manuscript. R.F. and C.C-R provided 10% or more of patients to the registry and reviewed the results. All authors contributed towards critical revision of the manuscript and approved the final draft.

Corresponding author

Correspondence to Paul J. Maglione.

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The authors declare that they have no conflict of interests.

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Weinberger, T., Fuleihan, R., Cunningham-Rundles, C. et al. Factors Beyond Lack of Antibody Govern Pulmonary Complications in Primary Antibody Deficiency. J Clin Immunol 39, 440–447 (2019). https://doi.org/10.1007/s10875-019-00640-5

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  • DOI: https://doi.org/10.1007/s10875-019-00640-5

Keywords

  • Primary antibody deficiency
  • interstitial lung disease
  • asthma
  • common variable immunodeficiency
  • x-linked agammaglobulinemia