Lung Disease in Primary Antibody Deficiencies

Abstract

Primary antibody deficiencies (PADs) are the most common form of primary immunodeficiency and predispose to severe and recurrent pulmonary infections which can result in chronic lung disease including bronchiectasis. Chronic lung disease is among the most common complications of PAD and a significant source of morbidity and mortality for these patients. However, the development of lung disease in PAD may not be solely the result of recurrent bacterial infection or a consequence of bronchiectasis. Recent characterization of monogenic immune dysregulation disorders and more extensive study of common variable immunodeficiency has demonstrated that interstitial lung disease (ILD) in PAD can result from generalized immune dysregulation and frequently occurs in the absence of pneumonia history or bronchiectasis. This distinction between bronchiectasis and ILD has important consequences in the evaluation and management of lung disease in PAD. For example, treatment of ILD in PAD typically utilizes immunomodulatory approaches in addition to immunoglobulin replacement and antibiotic prophylaxis which are the stalwarts of bronchiectasis management in these patients. Additionally, while all antibody deficient patients are at risk of developing bronchiectasis, ILD occurs in some forms of PAD much more commonly than others, suggesting that distinct but poorly understood immunological factors underlie development of this complication. Importantly, ILD can have earlier onset and may worsen survival more than bronchiectasis. Further efforts to understand the pathogenesis of lung disease in PAD will provide vital information for the most effective methods of diagnosis, surveillance, and treatment of these patients.

Interstitial lung disease in patients with common variable immunodeficiency disorders: several different pathologies?

“…In our study histological findings were variable, and there was no consistent pattern. Previous studies have suggested that these features are part of a spectrum, culminating in lymphoid malignancy [9,21], and this may be true for B cell ILD, but we provide some evidence for different pathologies, associated with varying outcomes and not always with malignancy, as a possible alternative. For example, the outcomes of those patients with organizing pneumonia were strikingly different from those with interstitial fibrosis or interstitial inflammation.…”

“…This absence of granulomata was despite 10 patients having well‐formed, biopsy‐proven, non‐caseating granulomata in other anatomical sites, including skin, brain, tongue, epiglottis, liver, bone marrow, gut, spleen or lymph nodes. This suggests that, in our patients, the aetiology of systemic granulomata, regardless of anatomical site, is separate from that of ILD and that we should avoid the term ‘granulomatous lymphocytic interstitial lung disease’ (GLILD), as it can be confusing if granulomata are not necessarily present in the lung .…”

Humoral immunodeficiencies: conferred risk of infections and benefits of immunoglobulin replacement therapy

“…9 When pulmonary infections are severe and recurrent, patients may develop irreversible lung damage such as bronchiectasis, which occurs in one-third or more of patients. 7,10,11 Mycoplasma and Ureaplasma are under recognized causes of infections in these patients and may involve atypical locations such as the joints. Notably, Ig replacement therapy has been shown to reduce the incidence of pneumonia, the onset of bronchiectasis, and other severe respiratory tract infections in CVID, although its role in limiting sinusitis is less clear.…”

The Lung in Dysregulated States of Humoral Immunity

“…Lung granulomatosis may be part of a systemic granulomatosis with extrathoracic involvement simulating sarcoidosis [37,38,39]. However, extrathoracic granulomas do not predict the granulomatous nature of the associated ILD [40]. Patients with GLILD usually present with dyspnea, cough, and crackles [34,37].…”