Immunosuppressive therapy after human lung transplantation

Abstract

numbers of lung transplantation (LTx) were performed with or without induction therapy with antilymphocyte antibodies, monoclonal anti-CD3 antibody or anti-interleukin-2-receptor monoclonal antibodies. It remains to be established if induction therapy after LTx is beneficial or deleterious for long-term graft and patient survival.The vast majority of lung transplant recipients receive a triple-drug maintenance regimen including a calcineurin inhibitor, a cell-cycle inhibitor and steroids. Equal proportions receive cyclosporin A (CsA) and tacrolimus (Tac). There is also a trend to prescribe mycophenolate mofetil (MMF) instead of azathioprine (Aza). Steroid withdrawal is uncommon even 5 yrs after transplantation.The superiority of Tac over CsA as a maintenance agent has not been established to date, and the administration of MMF instead of Aza in combination with CsA and steroids did not improve graft or patient survival in a recent international, prospective, randomised, controlled trial.Shift from cyclosporin A to tacrolimus has emerged as the first treatment step of refractory acute rejection followed by high-dose steroids or antilymphocyte agents, total lymphoid irradiation or photopheresis. The treatment of chronic rejection remains deceptive and includes varied strategies such as modification of the maintenance regimen, addition of inhaled immunosuppressants and/or total lymphoid irradiation and photopheresis. Eur Respir J 2004; 23: 159-171.

Alemtuzumab in the Treatment of Refractory Acute Rejection and Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

“…Consequently, treatments have primarily focused on augmented T-cell-based immunosuppression, such as changes in calcineurin inhibitor or the addition of antithymocyte globulin (ATG) (7,8). Despite these therapies, rates of rejection and BOS remain high, and alternative treatments are desperately needed to improve overall posttransplant outcomes.…”

Lung function early after lung transplantation is correlated with the frequency of regulatory T cells

“…In the present study, we found that the frequency of Treg cells in peripheral blood was positively correlated with improved early lung function, 3 weeks and 3 months after lung transplantation. Since it is known that the frequency and severity of acute rejection episodes and CMV/non-CMV infection episodes following pulmonary transplantation are correlated with the later development of BOS [2][3][4], an early regulatory phenotype, enabling better lung function parameters and rendering acute rejection less likely, could potentially predict a favorable long-term outcome. The severity of ischemia-reperfusion injury, which may not be dependent on an adaptive immune response, can interfere with lung function parameters [13], and could act as a confounding variable in this study.…”

“…Unfortunately, acute and chronic rejection episodes limit the midand long-term survival. The frequency and severity of acute rejection episodes and cytomegalovirus (CMV)/non-CMV infection episodes are associated with an increased risk of chronic rejection, which is synonymous with bronchiolitis obliterans syndrome (BOS) [2,3,4]. BOS is defined as an irreversible obstruction of the small airways and is routinely diagnosed and monitored with pulmonary function testing [4].…”

Chemokine-mediated angiogenesis: an essential link in the evolution of airway fibrosis?

“…Presently, prevention of graft rejection requires intensive, prolonged immunosuppression with corticosteroids, calcineurin antagonists, antimetabolites, and immune modulators (21). This approach, which is focused on the inflammatory component, has clear limitations, with significantly increased risks of opportunistic infection and a limited effect on angiogenesis.…”