Pathology of Lung Rejection: Cellular and Humoral Mediated

Acute rejection is an important risk factor for bronchiolitis obliterans syndrome, the clinical manifestation of chronic airway rejection in lung allograft recipients. Patients with acute rejection might be asymptomatic or present with symptoms that are not specific and can be also seen in other conditions. Clinical tests such as pulmonary function tests and imaging studies among others usually are abnormal; however, their results are also not specific for acute rejection. Histopathologic features of acute rejection in adequate samples of transbronchial lung biopsy of the lung allograft are currently the gold standard to assess for acute rejection in lung transplant recipients. Acute alloreactive injury can affect both the vasculature and the airways. Currently, the guidelines of the 2007 International Society of Heart and Lung Transplantation consensus conference are recommended for the histopathologic assessment of rejection. There are no specific morphologic features recognized to diagnose antibody-mediated rejection (AMR) in lung allografts. Therefore, the diagnosis of AMR currently requires a “triple test” including clinical features, serologic evidence of donor-specific antibodies, and pathologic findings supportive of AMR. Complement 4d deposition is used to support a diagnosis of AMR in many solid organ transplants; however, its significance for the diagnosis of AMR in lung allografts is not entirely clear. This chapter discusses the currently recommended guidelines for the assessment of cellular rejection of lung allografts and summarizes our knowledge about morphologic features and immunophenotypic tests that might help in the diagnosis of AMR.