Exosomes and the donor-specific molecules they carry can be used as diagnostic markers for the detection of allograft immune rejection that affects the survival rate of recipients after organ transplantation, overcoming the problem of poor sensitivity of traditional detection methods. As a leading researcher in the field of exosomes, Creative Biolabs is committed to providing clients with research services related to the application of exosomes for the diagnosis of allograft rejection, so as to advance the research progress of personalized and precise diagnosis of organ transplantation.

Advances in the Detection of Allograft Rejection

Organ transplantation is a viable treatment for a variety of advanced organ failure diseases. Recognition of allografts by the immune system and causing rejection often increases the risk of graft failure and hinders the therapeutic effect of transplantation. To precisely suggest the exact etiology of rejection, traditional assays are of use, including memory B cells, DSA (donor-specific antibodies), regulatory immune cells, and follicular helper T cells that mediate B cell proliferation and differentiation. Detection of immune status after organ transplantation by using CD4⁺ T cells, CD8⁺ T cells, and CD4/CD8 T cell ratio can be used to assess the occurrence of rejection. However, the poor specificity and sensitivity of the indicators lead to abnormal indicator responses lagging behind the irreversible damage that has already occurred in the organ, such as a negative serum DSA indicator in a patient whose pathological biopsy shows the occurrence of rejection of the transplanted organ. This impedes the control and performance of the desired therapeutic effect of organ transplantation. Exosomes are present in various body fluids and assist in the completion of a variety of important physiological and pathological processes such as protein secretion, antigen presentation, pathogen transfer, and tumor evolution by transporting active functional molecules between cells. Allograft rejection involves exosomes of donor graft origin carrying donor antigens from antigen-presenting cells to recipient lymphoid tissue and functioning as mediators of T-cell activation. Therefore, exosomes can be applied for early diagnosis and longitudinal detection of immune rejection and are important biomarkers for responding to the physiological status of the recipient after organ transplantation, with the benefits of accuracy, convenience, and non-invasive.

Fig.1 Exosome signaling is a phenomenon that plays a key role in intercellular communication. (Konstantinov & Yong, 2018)

Allograft Rejection Detection-Applied Exosomes in Creative Biolabs

Donor-derived specific exosomes maintain some of the biological properties of the donor and may serve as a novel biomarker resource for allograft rejection. For example, the detection of immature dendritic cell-derived exosomes may respond to their induction of immune tolerance in cardiac grafts, while regulatory T cell (Treg)-derived exosomes are used to assess the survival time of transplanted kidneys and the damage to kidney tissue by reduced immune cells. In addition, the cargo carried by exosomes causes changes associated with the onset of immune rejection and is another important basis for detecting allograft rejection. For example, studies have detected exosomes expressing autoantigens such as myosin and wave proteins in sera from the rejection group of heart transplant animal experiments. Exosomes of peripheral blood origin from patients with occlusive fine bronchiectasis syndrome express donor human leukocyte antigens, lung autoantigens, and cell adhesion molecules on their surface after lung transplantation. An elevated proportion of IL-21-producing Tfh-derived exosomes can be detected in peripheral blood after renal transplant rejection, accompanied by significant changes in cytotoxic T lymphocyte-associated antigen-4 on the surface of exosomes. Serum cfDNA is derived from exosomes, and 93% of plasma DNA accumulates in exosomes. Analysis of cfDNA levels in exosomes can be used to assess the stability of graft function. Although a small percentage of Treg, follicular regulatory T cells, and regulatory plasma cells are present in peripheral blood changes that occur after the onset of rejection are difficult to detect significantly. It is promising that their derived exosomes and specific markers can be used as a diagnostic basis with high sensitivity and in contrast, have a better application in response to allograft rejection.

Fig.2 Donor-derived exosomes via the semidirect pathway stimulate donor antigen-presenting cells and induce production of antibodies to self-antigens. (Ravichandran, 2019)

The in-depth understanding of the exosome field and its application to the assessment of allograft rejection has advanced detection from the traditional cellular level to the nano and molecular level, significantly improving diagnostic specificity and accuracy. With the aim of discovering more exosome-related biomarkers that meet the need to advance diagnostic and risk prediction studies of rejection, Creative Biolabs offers comprehensive exosome isolation and analysis solutions to help clients investigate the use of exosomes in the diagnosis of allogeneic transplant rejection. Please feel free to contact us.

References

1. Konstantinov, I.E.; Yong, M.S. Exosome signaling: A ubiquitous process in rejection and regeneration? J Thorac Cardiovasc Surg. 2018, 155(6): 2490-2491.
2. Ravichandran, R.; et al. The role of donor-derived exosomes in lung allograft rejection. Hum Immunol. 2019, 80(8): 588-594.

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