What causes acute rejection of a lung transplant and how is it managed?

Updated: Aug 19, 2019
  • Author: Bryan A Whitson, MD, PhD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Answer

Acute rejection is the host's response as the host recognizes the graft as foreign. The elements of the major histocompatability complex (MHC) are the factors responsible for recognizing the grafted organ and initiating cell-mediated inflammation. Two major classes of HLA antigens exist, and these are divided into class I and class II. Class I are HLA-A, HLA-B, and HLA-C; these are expressed on nearly all cells. They interact with CD8+ and T cells. Class II antigens (HLA-DP, HLA-DQ, HLA-DR) are expressed on specific cells, such as B lymphocytes, mononuclear phagocytes, and dendritic cells.

Acute rejection is diagnosed by clinical and histological criteria. The clinical criteria commonly are adopted for diagnosis in the early postoperative period. The features of acute rejection are dyspnea, fatigue, dry cough, low-grade fever, a decrease in oxygenation of greater than 10 mm Hg, the development of new or changing radiographic opacities, and a decrease in FEV1 of more than 10% below baseline value. Infections are the other most common differential diagnoses and cause significant morbidity in the early postoperative period; therefore, they must be excluded. Because the clinical criteria present later, when the acute rejection is more severe, they may be nonspecific in the early stages and many centers confirm the presence of rejection histologically.

Acute rejection is classified into five grades based on the severity and extent of the perivascular lymphocytic infiltration. The range is from no significant abnormality (grade A0) to severe abnormality (grade A4), in which extensive involvement of the interstitium and air space is present over and above, pneumocyte damage is present, and vasculitis (and even parenchymal infarction) are present. [53]

The clinical course of acute rejection can be variable. Most individuals develop at least one episode of acute rejection within the first 3 months. A significant number of patients are asymptomatic and are diagnosed by surveillance transbronchial biopsy. Chest radiographs may be helpful because ill-defined perihilar and lower lobe opacities, along with septal lines and pleural effusions, may suggest acute rejection.

Episodes of acute rejection are prevented by induction and maintenance of satisfactory immunosuppression. Most centers routinely use a triple immunosuppressive regimen, consisting of corticosteroids, mycophenolate mofetil (MMF) and tacrolimus.

The mainstay of therapy for acute rejection is pulse intravenous methylprednisolone, followed by higher oral prednisone doses. Tacrolimus and MMF are maximized. Methylprednisolone is used in a dose of 500-1000 mg/d intravenously, and oral prednisone is increased to 0.5-1 mg/kg/d with subsequent tapering. Steroid-resistant acute rejections may be treated with antilymphocyte therapy, which usually results in successful resolution of most cases of acute rejection.

Severe acute rejection within 10 days of lung tran Severe acute rejection within 10 days of lung transplantation (lower magnification). The typical histological findings are perivascular lymphocytic infiltrates. Courtesy of Zhaolin Xu, MD.
Severe acute rejection within 10 days of lung tran Severe acute rejection within 10 days of lung transplantation (high power). Courtesy of Zhaolin Xu, MD.
The transbronchial biopsy shows perivascular aggre The transbronchial biopsy shows perivascular aggregates of lymphocytes in the low-power field, which is indicating acute rejection in this patient 60 days after the lung transplant. This is grade II rejection. Courtesy of Zhaolin Xu, MD.
The transbronchial biopsy shows perivascular aggre The transbronchial biopsy shows perivascular aggregates of lymphocytes in the high-power field, which indicates acute rejection in this patient 60 days after the lung transplant. This is grade II rejection. Courtesy of Zhaolin Xu, MD.

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