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


OBJECTIVE
To investigate the expression of B-cell activating factor of tumor necrosis factor family (BAFF), a crucial mediator in the crosstalk 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 (FEV(1) = 57 ± 5% predicted), 14 control smokers (FEV(1) = 99 ± 2% predicted) and 8 nonsmokers (FEV(1) = 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.


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 nonsmokers (P < 0.05 for all). Among patients with COPD, BAFF(+) macrophages were inversely related to FEV(1) (P = 0.03, Spearman's rho [r(S)] = -0.48), FEV(1)/FVC (P = 0.02, r(S) = -0.50), and Pa(O(2)) 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.
Polverino
Francesca
F
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, 35128 Padova, Italy.
Baraldo
Simonetta
S
Bazzan
Erica
E
Agostini
Simone
S
Turato
Graziella
G
Lunardi
Francesca
F
Balestro
Elisabetta
E
Damin
Marco
M
Papi
Alberto
A
Maestrelli
Piero
P
Calabrese
Fiorella
F
Saetta
Marina
M
D056704:Adaptive Immunity; D053264:B-Cell Activating Factor / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D012720:Severity of Illness Index; D016037:Single-Blind Method; D012907:Smoking / Q000009:adverse effects / Q000276:immunology*
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D015415:Biomarkers