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.