Chronic Allograft Rejection: Epidemiology, Diagnosis, Pathogenesis, and Treatment

Abstract

Lung transplantation is a therapeutic option for patients with end-stage pulmonary disorders. Unfortunately, chronic lung allograft rejection, in the form of obliterative bronchiolitis and its clinical correlate bronchiolitis obliterans syndrome (BOS), continues to be highly prevalent and is the major limitation to long-term survival. The pathogenesis of BOS is complex and involves alloimmune and nonalloimmune pathways. The airway obstruction involved is classically progressive and unresponsive to treatment; however, the course is highly variable, and distinguishable phenotypes may exist. A better understanding of the risk factors and their relationship to the pathological mechanisms of chronic lung allograft rejection should lead to better pharmacological targets to prevent or treat this syndrome.

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

“…Additionally, many nonimmune mechanisms have also been implicated or suggested to play a role in BOS pathogenesis. These include airway injury due to primary graft dysfunction (PGD), gastro-oesophageal reflux (GOR), various infections, and airway ischaemia due to disruption of the bronchial circulation [14][15][16]. These ''non-immune'' factors may promote tissue damage and inflammation that in turn initiates and intensifies an alloimmune recipient response.…”

“…These ''non-immune'' factors may promote tissue damage and inflammation that in turn initiates and intensifies an alloimmune recipient response. Established OB displays variable evidence of inflammation, alloimmune reactions, autoimmunity, and fibroproliferation with airway obliteration that leads to allograft airway remodelling and loss of function [14][15][16]. OB may represent a final common end-point for a variety of forms of allograft injury.…”

International practical guidelines on diagnosis, prevention and treatment of bronchiolitis obliterans syndrome

“…сятся поражение дыхательных путей за счет ПДТ, ГЭР, различных инфекций, а также ишемия дыха тельных путей, вызванная механическим поврежде нием бронхиальных сосудов во время операции [14][15][16]. Эти неиммунные факторы могут вызывать по вреждение тканей и воспаление, при воздействии ко торых, в свою очередь, провоцируется и усиливается аллоиммунный ответ организма реципиента.…”

“…Эти неиммунные факторы могут вызывать по вреждение тканей и воспаление, при воздействии ко торых, в свою очередь, провоцируется и усиливается аллоиммунный ответ организма реципиента. В слу чае подтвержденного СОБ наблюдаются различные признаки воспаления, алло и аутоиммунные реак ции, пролиферация фиброзной ткани с облитерацией дыхательных путей, при этом ремоделируются дыха тельные пути трансплантата и снижаются его функ ции [14][15][16]. ОБ может быть финальным событием при различных формах поражения трансплантата.…”

Use of Flow Cytometry in the In Vitro and In Vivo Analysis of Tolerance/Anergy Induction by Immunocamouflage

“…[Li et al, 2011, Dallman, 2001, Suthanthiran & Strom, 1995 Three major patterns of rejection can be identified based on the rapidity of graft injury: hyperacute (minutes to hours), acute (days to weeks) and chronic (weeks to years). [Goldstein, 2011, Battaglia, 2010, Weigt et al, 2010 In hyperacute rejection not all parts of the graft are actively attacked. The primary site of injury is typically the vascular endothelium which can exhibit the ABO blood group antigens as well as MHC class I antigens.…”