Summary

Background:

Common variable immunodeficiency (CVID) is the most common clinically significant primary immunodeficiency disorder, typically presenting with hypogammaglobulinemia and recurrent infections. Mechanistically, CVID is caused by abnormal B-cell maturation or function. These abnormalities lead to an impaired ability to generate a normal quantity or diversity of antibodies and an impaired response to neo-antigens. In addition to the resulted immunodeficiency, CVID can also involve immune dysregulation affecting different organ systems, with the lungs being one of the more commonly involved organs. Granulomatous lymphocytic interstitial lung disease (GLILD) is a challenging and well known CVID-related complication. It is associated with high morbidity and increased risk of mortality.

Objectives:

To describe the clinical and immunological features of five CVID patients with radiologic and/or pathologic features consistent with granulomatous lymphocytic interstitial lung disease.

Methods:

We conducted a review of clinical, laboratory, imaging, and pathology data, as well as B-cell and T-cell immunophenotyping of patient PBMCs, focusing on unique characteristics of CVID GLILD patients.

Results:

CVID GLILD patients showed several clinical characteristics, including multiorgan involvement with cytopenias and lymphoproliferation but without significant gastrointestinal involvement. B-cell phenotyping showed abnormal B-cell maturation and development with severely impaired class switching. In addition, unique T-cell phenotype with low to near-absent naive CD4⁺ T cells was observed.

Conclusions:

Lung involvement in the form of GLILD is associated with significant co-morbidity and typical B-cell and T-cell immunophenotyping. Patients should be actively screened for the possibility of GLILD, especially when regularly performed lymphocyte immunophenotyping suggests similar patterns.