B-cell immunophenotyping in patients with GL-ILD (granulomatous interstitial lung disease) associated with CVID (common variable immune deficiency)

Introduction: Granulomatous interstitial lung disease (GL-ILD) develops in a subset of patients with common variable immunodeficiency (CVID) and is commonly confused with sarcoidosis. Little is known about the immunophenotyping of T and B lymphocyte subsets in GL-ILD. We reviewed the charts of four patients with CVID and GL-ILD. Methods: The presentation, laboratory and imaging studies, and treatment recommendations were reviewed. Each patient presented with thrombocytopenia and splenomegaly, and was subsequently found to have CVID and GL-ILD. Two patients, an 18 yr/M (#1), and a 12 yr/M (#2), presented with Evan's Syndrome. Results: All patients demonstrated significant hypogammaglobulinemia. Chest CTs were obtained in all patients and demonstrated diffuse nodular opacities. All patients underwent BAL and bronchoscopy to rule out an acute or chronic infection in addition to immunostaining and pathology studies on a lung biopsy sample. Tissue samples were obtained to confirm the diagnosis of GL-ILD in three out of four patients. Finally, B-Cell Immunophenotyping was obtained for all patients and showed decrease in total memory B-Cells (CD27+),especially low class switched memory B Cells (CD27+M-D-). Conclusions: These four cases illustrate the association between low class switched memory B Cells with GL-ILD in CVID patients. Specifically, it was found that all patients had decreased percent (3/4) or decreased absolute number (4/4) of class switched memory B Cells. B cell immunophenotyping may therefore be a useful tool for identifying patients with CVID and granulomatous disease. Implications for early identification include early initiation of specific treatment regimens, since this subset of patients may have a poorer prognosis and decreased survival when compared to their granuloma-free CVID counterparts. In this specific population of CVID patients, the combination of Rituximab and Azathioprine has been shown in preliminary studies to result in improvement in pulmonary function tests and lung disease. The combination of low serum IgA levels, splenomegaly and low class switched memory B cells can be used to create a prediction model for the diagnosis of GL-ILD in CVID patients in future. (Table presented).