A novel insight into adaptive immunity in chronic obstructive pulmonary disease: B cell activating factor belonging to the tumor necrosis factor family

Rationale: Chronic obstructive pulmonary disease (COPD) is a disorder characterized by an abnormal inflammatory response that persists even after smoking cessation, yet the underlying mechanisms are not fully understood. Objectives: To investigate the expression of B-cell activating factor of tumor necrosis factor family (BAFF), a crucial mediator in the cross-talk between innate and adaptive immune responses, in patients with COPD and to explore its correlation with disease severity. Methods: Using immunohistochemistry, expression of BAFF was examined in lung specimens from 21 smokers with COPD (FEV₁ = 57 ± 5%predicted), 14 control smokers (FEV ₁= 99 ± 2% predicted) and 8 nonsmokers (FEV₁ = 104 ± 4% predicted). BAFF was quantified in alveolar macrophages and alveolar walls, in bronchiolar and parenchymal lymphoid follicles, and in peripheral airways and pulmonary arterioles. Measurements and Main Results: In alveolar macrophages and parenchymal lymphoid follicles, BAFF expression was increased in smokers with COPD compared with control smokers and nonsmokers (P < 0.05 for all comparisons). In both compartments, BAFF was also up-regulated in control smokers as compared with nonsmokers (P = 0.03 and P < 0.01). Moreover, BAFF was overexpressed in bronchiolar lymphoid follicles, alveolar walls, peripheral airways, and pulmonary arterioles from smokers with COPD compared with non-smokers (P < 0.05 for all). Among patients with COPD, BAFF⁺ macrophages were inversely related to FEV₁ (P = 0.03, Spearman's rho [r_S] = -0.48), FEV₁/FVC (P = 0.02, r_S = -0.50), and Pa_O2 values (P = 0.01, r_S = -0.55). Conclusions: This study demonstrated overexpression of BAFF in peripheral lung of patients with COPD, mainly in alveolar macrophages and lymphoid follicles. Moreover, BAFF expression was correlated to the degree of lung function impairment and hypoxia, suggesting that it may have a possible impact on disease severity.