after liver transplantationGraft versus host disease (GVHD)Detection
Graft versus-host disease (GVHD) is a rare complication after liver transplantation, with an incidence rate of <1% and a very high mortality rate of approximately 85%. GVHD is a destructive cellular immune response produced by immunocompetent donor WBCs within the graft against recipient tissue. It usually occurs 2 to 8 weeks after surgery and can involve the skin, gastrointestinal tract, and bone marrow. Typical clinical manifestations include rash, fever, diarrhea, and pancytopenia[1]。
The incidence of GVHD after liver transplantation can be divided into three stages[2]. The first stage is when the recipient is in a relatively low immune state due to pre-transplant liver disease, the physiological stress of surgery, and the use of post-transplant immunosuppressants (IS). The second stage is when donor lymphocytes are activated upon interaction with recipient antigen-presenting cells, triggering IL-2-dependent proliferation, primarily Th1 differentiation. The third stage is when cytotoxic donor T lymphocytes target antigens expressed by the recipient tissue, resulting in cell death and tissue dysfunction. Further activation of donor lymphocytes is mediated by cytokines released by targeted host cells. The "cytokine-injury-cytokine" cycle will lead to the occurrence of inflammatory storm and ultimately lead to the occurrence of GVHD[3,4]. In addition, the destruction of the recipient's skin, bone marrow, and mucosal epithelium further aggravates the recipient's immunocompromised state.[2]。
Diagnosis of acute GVHD There is currently no widely accepted clinical or laboratory diagnostic test for GVHD, and diagnosis and treatment are often delayed. Usually when GVHD is diagnosed clinically, the patient's condition is very poor. Therefore, early screening and diagnosis of GVHD is particularly critical. Studies have shown that the level of donor-derived cell-free DNA in the peripheral blood of recipients increases significantly during the onset of GVHD. Therefore, this indicator can be used for rapid diagnosis of GVHD and monitoring of treatment response.[5]。
This test uses second-generation gene sequencing technology to capture and detect cells derived from donor tissues in the patient's peripheral blood, and uses the company's independently developed bioinformatics algorithm model GVHD-NIT to assess the risk of graft-versus-host disease (GVHD).
References:
[1] Chinese expert consensus on diagnosis and treatment of acute graft-versus-host disease after liver transplantation (2024 edition)
[2] Taylor AL, Gibbs P, Bradley JA. Acute graft versus host disease following liver transplantation: the enemy within [J]. Am J Transplant, 2004, 4(4): 466-74.DOI:10.1111/j.1600-6143.2004.00406.x.
[3] Hill GR, Koyama M. Cytokines and costimulation in acute graft-versus-host disease [J]. Blood, 2020, 136(4): 418-28.DOI:10.1182/blood.2019000952.
[4] Martinez-Cibrian N, Zeiser R, Perez-Simon JA. Graft-versus-host disease prophylaxis: Pathophysiology-based review on current approaches and future directions [J]. Blood Rev, 2021, 48: 100792.DOI:10.1016/j.blre.2020.100792.
[5] Lewis D, Glehn-Ponsirenas R, Gulbahce N, et al. High levels of donor-derived cell-free DNA in a case of graft-versus-host-disease following liver transplantation [J]. Am J Transplant, 2022, 22(3): 973-6.DOI:10.1111/ajt.16894.