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

Tamar Weinberger, Ramsay L Fuleihan, Charlotte Cunningham-Rundles, Paul J. Maglione*

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)440-447
Number of pages8
JournalJournal of Clinical Immunology
Volume39
Issue number4
DOIs
StatePublished - May 15 2019

Fingerprint

Common Variable Immunodeficiency
Interstitial Lung Diseases
Lung
Asthma
Antibodies
Respiratory Tract Infections
Agammaglobulinemia
Bronchiectasis
Autoimmunity
Registries
Immunoglobulins
Pneumonia
T-Lymphocytes
Passive Immunization
Age of Onset
Immunoglobulin A
Lung Diseases
Immunoglobulin M
B-Lymphocytes
Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Weinberger, Tamar ; Fuleihan, Ramsay L ; Cunningham-Rundles, Charlotte ; Maglione, Paul J. / Factors Beyond Lack of Antibody Govern Pulmonary Complications in Primary Antibody Deficiency. In: Journal of Clinical Immunology. 2019 ; Vol. 39, No. 4. pp. 440-447.
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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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Factors Beyond Lack of Antibody Govern Pulmonary Complications in Primary Antibody Deficiency. / Weinberger, Tamar; Fuleihan, Ramsay L; Cunningham-Rundles, Charlotte; Maglione, Paul J.

In: Journal of Clinical Immunology, Vol. 39, No. 4, 15.05.2019, p. 440-447.

Research output: Contribution to journalArticle

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T1 - Factors Beyond Lack of Antibody Govern Pulmonary Complications in Primary Antibody Deficiency

AU - Weinberger, Tamar

AU - Fuleihan, Ramsay L

AU - Cunningham-Rundles, Charlotte

AU - Maglione, Paul J.

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