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

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.

Development of pulmonary abnormalities in patients with common variable immunodeficiency: associations with clinical and immunologic factors.

BACKGROUND: Patients with common variable immunodeficiency (CVID) have low serum IgG, IgA, and/or IgM levels and recurrent airway infections. Radiologic pulmonary abnormalities and impaired function are common complications. It is unclear to what extent IgG replacement treatment prevents further pulmonary damage and how factors beside infections may contribute to progression of disease. OBJECTIVES: To study the development of pulmonary damage and determine how clinical and immunologic factors, such as serum IgG, may contribute to possible changes. METHODS: In a retrospective, longitudinal study of 54 patients with CVID already treated with immunoglobulins, we examined changes of lung function and findings on high-resolution computed tomography (HRCT), obtained at 2 time points (the date of the last pulmonary function measurement before April 2005 [T1] and the date of the measurement performed closest to 5 years earlier [T0]) 2 to 7 years apart and explored possible relations to clinical and immunologic factors such as levels of IgG, tumor necrosis alpha (TNF-alpha), and mannose-binding lectin (MBL) in serum. RESULTS: Despite a mean (SD) serum IgG level of 7.6 (2.3) g/L for all the patients during the entire study period, lung function decreased from T0 to T1. The combination of a low serum IgA level and serum MBL was associated with the presence of bronchiectasis and lower lung function and with worsening of several HRCT abnormalities from T0 to T1. Increased serum levels of TNF-alpha were related to deterioration of gas diffusion. A mean serum IgG level less than 5 g/L between T0 and T1 was associated with worsening of linear and/or irregular opacities seen on HRCT. CONCLUSION: For a period of 4 years, lung function and HRCT deteriorated in CVID patients treated with immunoglobulins.

High resolution computed tomography and pulmonary function in common variable immunodeficiency.

Patients with common variable immunodeficiency (CVID) have impaired production of immunoglobulins and hence recurrent airway infections, which in turn may lead to radiological changes and impaired lung function. Uncertainty exists about the nature and frequency of the radiological and the physiological abnormalities, and how they relate to each other. We reassessed high resolution computed tomography (HRCT) images in 65 patients, reported results from previously measured lung function tests, and studied relations between radiology, function and clinical variables. Airway obstruction, ventilatory restriction and impaired gas diffusion was found in 40, 34 and 21% of the patients, respectively. HRCT abnormalities were present in 94% of the subjects, mild changes being the most common. Bronchial wall thickening, found in two thirds of the patients, was related to airway obstruction and impaired gas diffusion. Linear and/or irregular opacities, the most frequent interstitial abnormality, was related to impaired gas diffusion. Bronchiectasis was found in more than half, but only severe bronchiectasis was related to airway obstruction. Since bronchial wall thickening and linear and/or irregular opacities are both frequent and important determinants of impaired pulmonary function, more attention should be given to these features in the follow up of CVID patients.