Abstract
Background: COPD shares some features with autoimmune diseases, such as a blunted regulatory T-cell (Tregs) activity allowing autoimmune reactions. B cell Activating Factor (BAFF) is a key factor modulating B cell homeostasis, and is overexpressed in B-cells lymphoid follicles of lungs from COPD patients. We hypothesize that BAFF upregulation in B cells is due to a reduced activity of TRegs translated as a lower production of BAFF in these cells.
Methods: BAFF expression in B-lymphocytes and Tregs from bronchoalveolar lavage (BAL) and blood was quantified by Flow Cytometry in 38 patients with COPD (mean±SD,FEV1=68±14%pred); 17 smokers with normal lung function (SC) (FEV1=104±15%pred) and 20 non-smokers (NSC) (FEV1=101±20%pred).
Results: In BAL, Tregs from COPD patients showed lower BAFF expression (Median, Range: 7, 0-32 Mean Fluorescence, MF) as compared to SC (17, 10-27; p=2×10-4) and NSC (14, 10-22; p=0,005).
Conversely, BAFF was overexpressed in B lymphocytes from COPD patients (50, 23-121) when compared to SC (12, 0-28; p=6×10-5) and NSC (20, 6-95; p=0,001).
In blood, COPD had less Baff+ TRegs (10, 0-22,5) and more Baff+ B lymphocytes (23, 5,6-102) compared to NSC(12, 10-5; 13, 10-53; p=0,01; p=0,006, respectively). To test whether cigarette smoke (CS) influences BAFF expression, we cultivated blood mononuclear cells from 4 NSC with 3% and 7%CS. At 24 hours, BAFF was increased in B lymphocytes stimulated with CS 3% and even more with CS 7% with respect to the control (p=0,03; p=0,02, respectively).
Conclusion: In COPD there is a blunted expression of BAFF in TRegs that leads, partly due to cigarette smoke, to its excessive production by B lymphocytes, showing an imbalance of its functioning that is a common feature of several autoimmune diseases.
- © 2011 ERS
