Towards understanding the role of autoreactivity in COPD

The role for autoimmunity in the pathogenesis of COPD is controversial, and the identity of putative autoantigens is subject to debate. In order to examine the role for autoantibodies in COPD, we cloned the complete variable light and heavy chains from single-cell sorted IgG or IgA-positive activated memory B cells isolated from COPD and control lung tissue, and expressed these as complete human Ig monoclonal antibodies (HumAbs). These HumAbs were tested for autoreactivity by histology using lung tissue sections of COPD patients and healthy controls and lung cell lines. In addition, serum of COPD patients and healthy controls was used to determine binding of antibodies to epithelial, fibroblast, and endothelial cell lines. The HumAbs stained multiple cells and structures in lung tissue sections such as smooth muscles cells, epithelial cells, and the adventitia. The cell lines examined thus far, two epithelial cell lines, were also stained by the HumAbs. Serum IgA and IgG antibody titers against epithelial, fibroblast, and endothelial lung cell lines overlapped considerably between patients and controls. As a consequence, the differences between titers of patients and controls were marginally significant. Interestingly, however, some COPD patients had a high serum antibody titer against one cell line, but a low titer against another cell line. Our results illustrate the complexity of autoreactivity in COPD in that concomitant with the preferential binding of different types of lung cells by antibodies in serum of COPD patients, individual antibodies may also target multiple cells and structures in the lung.