Immunodeficiencies and CFTR dysfunction: results from a systematic screening in a cohort of adults with cystic fibrosis and CFTR-related disorders

Abstract

Background: Immunodeficiencies (IDs) are conditions caused by immune system dysfunctions which predispose to chronic infections. Cystic fibrosis (CF) patients are characterized by the presence of bronchiectasis filled with hyper-viscous secretions that constitute the ideal environment for infections. Although CF and IDs might share similarities in the pathophysiological mechanism of bronchiectasis development, they each offer different treatment options. We hypothesize that the introduction of a bundle of tests would increase the number of ID diagnoses among adults with Cystic Fibrosis Transmembrane conductance Regulator (CFTR) dysfunction. Objectives: The primary objectives of this study were (1) assessing the prevalence of IDs in CF and (2) defining clinical characteristics of adults with both CF and IDs. The secondary objectives were: (1) assessing the prevalence of IDs in CFTR-Related Disorder (CFTR-RD) patients; (2) comparing the prevalence of IDs in CF and CFTR-RD; (3) comparing the prevalence of treatable IDs in CF and CFTR-RD. Design: We conducted an observational, prospective, consecutive study on a cohort of 190 adult patients affected by CF or CFTR-RD. Methods: Blood samples underwent a standardized immunological screening, including complete white blood count, IgG, IgA, IgM, IgG subclasses, total IgE, lymphocyte subsets, and HIV test. Comprehensive clinical history was assessed to identify risk factors for secondary IDs. Results: We identify a high prevalence of immunodeficiencies among the entire cohort: 34 (20.1%) CF patients and 10 (47.6%) CFTR-RD patients are diagnosed with IDs via a blood screening. No statistically significant difference in terms of clinical characteristics was found between immunocompromised and immunocompetent CF patients. Conclusion: We identify a high prevalence of immunodeficiencies in both CF and CFTR-RD.