Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in Common Variable Immunodeficiency (CVID): A Multicenter Retrospective Study of Patients From Italian PID Referral Centers

• Published in: Frontiers in immunology 2021-03, Vol.12, p.627423-627423
• Main Authors: Cinetto, Francesco, Scarpa, Riccardo, Carrabba, Maria, Firinu, Davide, Lougaris, Vassilios, Buso, Helena, Garzi, Giulia, Gianese, Sabrina, Soccodato, Valentina, Punziano, Alessandra, Lagnese, Gianluca, Tessarin, Giulio, Costanzo, Giulia, Landini, Nicholas, Vio, Stefania, Bondioni, Maria Pia, Consonni, Dario, Marasco, Carolina, Del Giacco, Stefano, Rattazzi, Marcello, Vacca, Angelo, Plebani, Alessandro, Fabio, Giovanna, Spadaro, Giuseppe, Agostini, Carlo, Quinti, Isabella, Milito, Cinzia
• Format: Article
• Language: English
• Subjects: autoimmune cytopenia; CD21lo B cells; CVID-ILD; DLCO; GLILD; Immunology; splenomegaly
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.627423

Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) is a severe non-infectious complication of Common Variable Immunodeficiency (CVID), often associated with extrapulmonary involvement. Due to a poorly understood pathogenesis, GLILD diagnosis and management criteria still lack consensus. Accordingly, it is a relevant cause of long-term loss of respiratory function and is closely associated with a markedly reduced survival. The aim of this study was to describe clinical, immunological, laboratory and functional features of GLILD, whose combination in a predictive model might allow a timely diagnosis. In a multicenter retrospective cross-sectional study we enrolled 73 CVID patients with radiologic features of interstitial lung disease (ILD) associated to CVID (CVID-ILD) and 125 CVID patients without ILD (controls). Of the 73 CVID-ILD patients, 47 received a definite GLILD diagnosis while 26 received a clinical-radiologic diagnosis of CVID related ILD defined as uILD. In GLILD group we found a higher prevalence of splenomegaly (84.8 vs. 39.2%), autoimmune cytopenia (59.6 vs. 6.4%) and bronchiectasis (72.3 vs. 28%), and lower IgA and IgG serum levels at CVID diagnosis. GLILD patients presented lower percentage of switched-memory B cells and marginal zone B cells, and a marked increase in the percentage of circulating CD21lo B cells (14.2 vs. 2.9%). GLILD patients also showed lower total lung capacity (TLC 87.5 vs. 5.0%) and gas transfer (DLCO 61.5 vs. 5.0%) percent of predicted. By univariate logistic regression analysis, we found IgG and IgA levels at CVID diagnosis, presence of splenomegaly and autoimmune cytopenia, CD21lo B cells percentage, TLC and DCLO percent of predicted to be associated to GLILD. The joint analysis of four variables (CD21lo B cells percentage, autoimmune cytopenia, splenomegaly and DLCO percent of predicted), together in a multiple logistic regression model, yielded an area under the ROC curve (AUC) of 0.98 (95% CI: 0.95-1.0). The AUC was only slightly modified when pooling together GLILD and uILD patients (0.92, 95% CI: 0.87-0.97). we propose the combination of two clinical parameters (splenomegaly and autoimmune cytopenia), one lung function index (DLCO%) and one immunologic variable (CD21lo%) as a promising tool for early identification of CVID patients with interstitial lung disease, limiting the use of aggressive diagnostic procedures.