PerspectiveAntibody-mediated rejection in lung transplantation: Myth or reality?
Section snippets
Hyperacute rejection
Evidence for the concept of AMR presenting with hyperacute rejection, albeit a rare phenomenon, is more compelling. In 1996 Frost et al8 described the first convincing case of clinical hyperacute rejection, which was corroborated by a positive, donor–antigen-specific immunoglobulin (Ig) G-mediated lymphocytotoxic crossmatch, and compatible histopathologic, immunofluorescent, and electron microscopic features. Features of diffuse alveolar damage, neutrophilic infiltrates, and endothelial and
Acute rejection
Evidence for the role of AMR as a potential modality of acute rejection is conflicted and relies on the histopathologic definition of changes that can be ascribed to AMR vs those that are deemed compatible with ACR. Capillaritis, or more correctly, capillary injury, appears to be one of the most definitive findings suggestive of AMR in the literature, the concerns of the current LRSG notwithstanding. Of course, the level of concordance between pathologists in grading AMR is untested. In 1996
Chronic rejection
In concert with other solid organ transplants, it remains probable that AMR is indeed a lead candidate for an etiologic role in the insidious onset and progression of graft dysfunction categorized as chronic rejection, which in the lung is manifest as bronchiolitis obliterans syndrome (BOS). A number of authors have postulated that BOS is the result of humoral and cellular immune responses developed against major histocompatibility complex molecules expressed by airway epithelial cells of the
Non-HLA antibodies
If HLA mismatch and anti-HLA antibodies demonstrate a small effect, it is possible that non-HLA antibodies may have a significant effect. An early, exciting report in 1995 by Smith et al25 from Harefield showed that anti-epithelial cell antibodies (AECAs) detectable in a microcytotoxicity assay (but not by Western blotting) before single-lung transplantation were associated with a decrease in 1-year graft survival of 56% for AECA-positive recipients vs 78% for AECA-negative recipients (p =
The role of complement
AMR is a better-defined cause for cardiac and renal graft dysfunction, where C4d deposition, a stable component of complement activation, inversely correlates with graft survival. Magro et al30 examined biopsy specimens from 23 lung transplant recipients in an attempt to correlate clinical status and morphologic findings with the pattern of C4d deposition. In patients with symptomatic acute rejection, all specimens showed light microscopic and immunofluorescent evidence compatible with AMR. The
Conclusion
Although some questions are unanswered regarding the true incidence, severity, and significance of AMR after lung transplantation, biologically plausible clinical phenotypes have been described for hyperacute and acute AMR. Other causes of acute lung injury such as aspiration pneumonitis and hemorrhagic viral infection must be excluded in the acute circumstance, but prompt action to manage potentially life-threatening graft dysfunction is critical for the practitioner, who must be guided by the
Disclosure statement
Allan R. Glanville is the global principal investigator for the CeMyLungs Investigator Driven study, for which his institution will receive grant support to conduct the study from Novartis Pharmaceuticals (not to exceed €2.4 million).
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