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Review
. 2017 Dec;9(12):5440-5457.
doi: 10.21037/jtd.2017.11.83.

Acute rejection

Mark Benzimra  1 , Greg L Calligaro  2 , Allan R Glanville  1
Affiliations
Review

Acute rejection

Mark Benzimra et al. J Thorac Dis. 2017 Dec.

Erratum in

  • Erratum to acute rejection.
    [No authors listed] [No authors listed] J Thorac Dis. 2018 Feb;10(2):E165. doi: 10.21037/jtd.2018.01.136. J Thorac Dis. 2018. PMID: 29608201 Free PMC article.

Abstract

Despite induction immunosuppression and the use of aggressive maintenance immunosuppressive regimens, acute allograft rejection following lung transplantation is still a problem with important diagnostic and therapeutic challenges. As well as causing early graft loss and mortality, acute rejection also initiates the chronic alloimmune responses and airway-centred inflammation that predispose to bronchiolitis obliterans syndrome (BOS), also known as chronic lung allograft dysfunction (CLAD), which is a major source of morbidity and mortality after lung transplantation. Cellular responses to human leukocyte antigens (HLAs) on the allograft have traditionally been considered the main mechanism of acute rejection, but the influence of humoral immunity is increasingly recognised. As with other several other solid organ transplants, antibody-mediated rejection (AMR) is now a well-accepted and distinct clinical entity in lung transplantation. While acute cellular rejection (ACR) has defined histopathological criteria, transbronchial biopsy is less useful in AMR and its diagnosis is complicated by challenges in the measurement of antibodies directed against donor HLA, and a determination of their significance. Increasing awareness of the importance of non-HLA antigens further clouds this issue. Here, we review the pathophysiology, diagnosis, clinical presentation and treatment of ACR and AMR in lung transplantation, and discuss future potential biomarkers of both processes that may forward our understanding of these conditions.

Keywords: Lung transplant; acute antibody rejection; cellular rejection; humoral rejection.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The direct and indirect pathways of allo-sensitisation. In the direct pathway, donor-derived MHC complexes, presented by donor-derived ‘passenger’ dendritic cells (antigen-presenting cells or APCs), are recognised directly by recipient T cells. In the indirect pathway, host APCs take up immunogenic proteins from apoptotic graft cells and present donor-derived processed peptides on host MHC to host T cells. MHC, major histocompatibility complex; APC, antigen presenting cell.
Figure 2
Figure 2
Trans-bronchial biopsies at high-power field demonstrating the different grades of rejection.
Figure 3
Figure 3
Trans-bronchial biopsy at high power magnification showing C4d capillary staining.
Figure 4
Figure 4
Classification of AMR according to the presence or absence of diagnostic certainty and presence (Clinical) or absence (Sub-clinical) of allograft dysfunction*. *Adapted from the 2016 pulmonary AMR consensus document of the ISHLT. AMR, antibody-mediated rejection.
See this image and copyright information in PMC

References

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