Abstract
Background: Common variable immunodeficiency disorder (CVID) is the most frequent symptomatic primary immunodeficiency. Previous studies indicates that a subgroup of CVID patients develop autoimmune diseases and granulomatous lesions in the lung. Circulatory Tregs (CD4+Foxp3+CD25high) are reduced in these patients.
Objective: to characterise brochoalveolar lavage (BAL) cell pattern and Treg counts in CVID with ILD versus healthy donors (HD).
Methods: the study included 32 CVID-patients and 31 HD. BAL differential cell counts and spontaneous TNF-alpha production by BAL cells were tested. Various Treg subpopulations were quantified by flow cytometry.
Results: BAL differential cell counts revealed a significant increase in total cell count (p<0.001), percent of lymphocytes (LF) (p<0.001), neutrophils (p<0.001), eosinophils (p<0.001), and CD20+B cells (p<0.001) in CVID versus HD. The percentage of Tregs in CVID with ILD was significant lower in BAL and PBMCs compared to the HD. There was a positive correlations between Treg percentage in BAL and PBMCs (p=0.02, r=0.8). Patients with low circulatory Treg counts had also low BAL Treg counts. In BAL there was a invers correlation (p<0.001, r=-0.6) between the % of LF in differential cytology and % of Treg in flowcytometry. The level of TNF-alpha in BAL supernatants was significantly higher (p=0.02) in CVID compared to HD.
Conclusion: CVID-ILD is associated with a significant lower number of BAL Tregs and an increase in spontaneous TNF-alpha production. Despite a CD19+B cell deficiency in peripheral blood, there is an increase in CXCR3+CD20+B cells in BAL.