Lung disease, T-cells and inflammation in common variable immunodeficiency disorders

Abstract

INTRODUCTION: Besides hypogammaglobulinemia and recurrent infections, abnormalities of T-cells might contribute to lung damage in common variable immunodeficiency disorders (CVID). MATERIALS AND METHODS: In 16 adult patients, the majority of whom had pulmonary abnormalities, we studied T-cell subsets and markers of inflammation in bronchoalveolar lavage fluid (BALF) and blood and their relations with pulmonary function and high resolution computed tomography (HRCT). RESULTS: We demonstrated that some of the lymphocyte abnormalities previously demonstrated in peripheral blood from CVID patients, such as low CD4/CD8 T-cell ratio, were also present in BALF. Moreover, low BALF CD4/CD8 ratio (≤ 1), found in seven patients, was significantly associated with higher blood CD8⁺ cell count and to lower values of the lung function variables; forced expiratory volume (FVC), total lung capacity (TLC), vital capacity (VC) and residual volume (RV) in % of predicted. The expression of the inflammatory markers HLA-DR and CCR5 on T-cells was significantly higher, and the expression of CCR7 significantly lower, in BALF compared to blood, possibly reflecting an inflammatory/cytotoxic T-cell phenotype within pulmonary tissue in CVID. Furthermore, patients with bronchiectasis had higher concentrations of the pro-inflammatory cytokine TNFα in plasma, compared to those without. CONCLUSION: Our findings suggest that inflammation and T-cell activation may be involved in the immunopathogenesis of pulmonary complications in CVID.