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.

Key Words::

• Hypogammaglobulinemia
• bronchoalveolar lavage
• chemokines
• bronchiectasis
• interstitial lung disease

Declaration of interest: Stina Gregersen has received funds for research from GlaxoSmithKline, AstraZeneca and Norsk Forening for Immunsvikt and received a fee for speaking at meetings sponsored by Octapharma. Bjørn Johansen has received a fee for speaking at meetings sponsored by GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim and Merck Sharp & Dome. The funding source had no role in interpretation of data, writing the report or decision to submit. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.