Decreased humoral immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease

慢性阻塞性肺病快速衰退患者支气管体液免疫反应降低

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作者:Antonino Di Stefano, Francesca Dossena, Isabella Gnemmi, Silvestro Ennio D'Anna, Paola Brun, Bruno Balbi, Alessio Piraino, Antonio Spanevello, Francesco Nucera, Vitina Carriero, Francesca Bertolini, Mauro Maniscalco, Ian M Adcock, Gaetano Caramori #, Fabio L M Ricciardolo #

Background

Identification of COPD patients with a rapid decline in FEV1 is of particular interest for prognostic and therapeutic reasons.

Conclusion

These data show an impaired humoral immune response in rapid decliners with COPD, marked by reduced epithelial secretory IgA and plasma cell numbers in the bronchial lamina propria. These findings may help in the prognostic stratification and treatment of COPD.

Methods

In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the expression and localization of inflammatory markers was measured in bronchial biopsies of patients with no lung functional decline (FEV1% + 30 ± 43 ml/year, n = 21), slow (FEV1% ml/year, - 40 ± 19, n = 14) and rapid decline (FEV1% ml/year, - 112 ± 53, n = 15) using immunohistochemistry. ELISA test was used for polymeric immunoglobulin receptor (pIgR) quantitation "in vitro".

Objective

To determine the expression of markers of inflammation in COPD patients with rapid functional decline in comparison to slow or no decliners.

Results

The expression of secretory IgA was significantly reduced in bronchial epithelium (p = 0.011) and plasma cell numbers was significantly reduced in the bronchial lamina propria (p = 0.017) of rapid decliners compared to no decliners. Bronchial inflammatory cell infiltration, CD4, CD8, CD68, CD20, NK, neutrophils, eosinophils, mast cells, pIgR, was not changed in epithelium and lamina propria of rapid decliners compared to other groups. Plasma cells/mm2 correlated positively with scored total IgA in lamina propria of all patients. "In vitro" stimulation of 16HBE cells with LPS (10 μg/ml) and IL-8 (10 ng/ml) induced a significant increase while H2O2 (100 μM) significantly decreased pIgR epithelial expression.

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