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. 2023 Sep 4:2:1248987.
doi: 10.3389/frtra.2023.1248987. eCollection 2023.

Extracellular vesicles: a potential new player in antibody-mediated rejection in lung allograft recipients

Sandhya Bansal  1 , Ashwini Arjuna  1 , Brian Franz  2 , Alexa Guerrero-Alba  1 , Jesse Canez  1 , Timothy Fleming  1 , Mohammad Rahman  1 , Ramsey Hachem  3 , T Mohanakumar  1
Affiliations

Extracellular vesicles: a potential new player in antibody-mediated rejection in lung allograft recipients

Sandhya Bansal et al. Front Transplant. .

Abstract

Identification of recipients with pre-existing antibodies and cross-matching of recipient sera with donor lymphocytes have reduced the incidence of antibody-mediated rejection (AMR) after human lung transplantation. However, AMR is still common and requires not only immediate intervention but also has long-term consequences including an increased risk of chronic lung allograft dysfunction (CLAD). The mechanisms resulting in AMR remain largely unknown due to the variation in clinical and histopathological features among lung transplant recipients; however, several reports have demonstrated a strong association between the development of antibodies against mismatched donor human leucocyte antigens [donor-specific antibodies (DSAs)] and AMR. In addition, the development of antibodies against lung self-antigens (K alpha1 tubulin and collagen V) also plays a vital role in AMR pathogenesis, either alone or in combination with DSAs. In the current article, we will review the existing literature regarding the association of DSAs with AMR, along with clinical diagnostic features and current treatment options for AMR. We will also discuss the role of extracellular vesicles (EVs) in the immune-related pathogenesis of AMR, which can lead to CLAD.

Keywords: antibody mediated rejection (AMR); chronic lung allograft dysfunction (CLAD); donor specific antibodies; extracellular vesicle (EV); lung transplanation.

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Conflict of interest statement

The author RH declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Diagrammatic reprentation of extracellular vesicle carrying CD9, CD63, CD81, TSG101, ALIX, tissue-specific markers (collagen V and K alpha1 tubulin in lung transplant; cardiac myosin and vimentin in cardiac transplant; fibronectin, collagen IV and perlecan in kidney transplant) (73). Images created using BioRENDER.
Figure 2
Figure 2
Diagrammatic representation of the mechanism of allograft rejection in lung transplant recipients (LTxRs) with antibody-mediated rejection (AMR). Extracellular vesicles from LTxRs with CLAD carry lower amounts of liver kinase B (LKB1) and AMPKα than those from stable LTxRs. Decreased levels of LKB1 downregulate AMPKα, which can potentially increase epithelial-to-mesenchymal transition followed by chronic lung allograft dysfunction and graft loss. Similarly EVs in AMR can also play a potential role involving LKB1 and AMPKα which can be further associated with development of CLAD followed by graft rejection, this hypothesis needs further investigation. Images created using BioRENDER.
See this image and copyright information in PMC

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