Identification and clinical association of anti-cytokeratin 18 autoantibody in COPD

The etiology of chronic obstructive pulmonary disease (COPD) remains unclear. A mechanism involving the autoimmune reaction in the pathogenesis of COPD has been proposed but not confirmed. The aim of this study was to investigate whether serum autoantibodies against pulmonary cellular proteins are present in COPD patients and to identify their autoantigens if possible. Samples from 50 COPD patients and 42 control subjects were studied. Circulating autoantibodies were detected by Western blot. Immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were used to identify the autoantigens. Autoantibodies against pulmonary cellular antigens were found in the sera of COPD patients. Specifically, an autoantibody against the 45-kDa human cytokeratin 18 protein was found in 76.0% of COPD patients and 23.8% of control subjects (p<0.001). Furthermore, the cytokeratin 18 autoantibody level was positively correlated with the FEV₁ (L) (p=0.013) and FEV₁ (%pred.) (p=0.043) values observed in COPD patients. This study identified the pulmonary epithelial cytokeratin 18 protein as a COPD-associated autoantigen and found that anti-cytokeratin 18 autoantibodies were prevalent in COPD patients. Our results support the hypothesis that humoral autoimmunity may be involved in the pathogenesis of COPD.