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Autoimmune Responses to Grafted Lungs: Immune Responses to a Native Collagen—Type V Collagen

Indiana University School of Medicine

Lung transplantation is the only definitive treatment modality for many forms of end-stage lung disease. However, the lung is rejected more often than any other type of solid organ allograft due to chronic rejection known as bronchiolitis obliterans (BO). Indeed, BO is the primary reason why the 5- and 7-year survival rates are worse than any other transplanted organs. Alloimmunity to donor antigens is established as the primary mechanism that mediates rejection responses. However, newer immunosuppressive regimens designed to abrogate alloimmune activation have not improved survival. Therefore, these data suggest that other antigens, unrelated to donor transplantation antigens, are involved in rejection. Utilizing human and rodent studies of lung transplantation, our laboratory has documented that a native collagen, type V collagen (col(V)), is a target of the rejection response. Since col(V) is highly conserved, these data indicate that transplant rejection involves both alloimmune and autoimmune responses. The role of col(V) in lung transplant rejection is described in this review article.

Key Words: autoimmunity • type V collagen • allorecognition • lung transplantation

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