Chronic obstructive pulmonary disease and emphysema are common destructive inflammatory diseases that are leading causes of death worldwide. Here we show that emphysema is an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 (T(H)1) responses, which correlate with emphysema severity. These findings link emphysema to adaptive immunity against a specific lung antigen and suggest the potential for autoimmune pathology of other elastin-rich tissues such as the arteries and skin of smokers.

Chronic obstructive pulmonary disease (COPD) and emphysema are chronic inflammatory diseases of the lung. Chronic exposure to cigarette smoke is the most common cause of COPD/emphysema however the pathogenesis is not fully understood. Innate immune cells like macrophages and neutrophils are thought to be the most critical factor in the disease pathogenesis. However, we have found that lung and peripheral blood T cells in patients with severe emphysema secrete Th1 cytokines and chemokines when stimulated with elastin peptides in vitro and they have increased anti-elastin antibody as compared to controls. Based on these human studies, we tested the hypothesis that elastin peptides can act as self-antigen and induce an autoimmune lung inflammation in mice. Mice were immunized intra-peritonealy with mouse elastin peptides and adjuvants. Like human COPD, we found increased numbers of activated macrophages and neutrophils as well as increased MMP9 and MMP12 in the airway fluid of elastin immunized mice. Hilar lymph node cells of elastin immunized mice produced more IFN-g upon restimulation with elastin peptides. Additionally, elastin immunized mice had increased anti-elastin antibody titer in the serum and increased IFN-g in the lungs. The establishment of the mouse model of elastin-mediated autoimmune lung inflammation will be critical in elucidating the role of adaptive immune system in pathogenesis of COPD/emphysema.