Biomarkers of graft-vs-host disease: Understanding and applications for the future

Abstract

Hematopoietic stem cell transplantation (HSCT) is widely performed as a treatment for malignant blood disorders, such as leukemia. To achieve good clinical outcomes in HSCT, it is necessary to minimize the unfavorable effects of acute graft- vs -host disease (GVHD) and induce the more tolerable, chronic form of the disease. For better management of GVHD, sensitive and specific biomarkers that predict the severity and prognosis of the disease have been intensively investigated using proteomics, transcriptomics, genomics, cytomics, and tandem mass spectrometry methods. Here, I will briefly review the current understanding of GVHD biomarkers and future prospects.

Prognostic Biomarkers for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study

“…Additionally, the endothelial dysfunction that results in VOD/SOS can also contribute to other conditions that may make identifying biomarkers specific to the diagnosis of VOD/SOS challenging [ 5 ]. Indeed, markers of endothelial injury identified as prognostic markers of VOD/SOS risk in this report, such as ICAM-1, VCAM-1, ANG-2, ST2, TIMP-1, and TM, have also been identified as potential biomarkers for other conditions associated with endothelial dysfunction [ 32 ].…”

“…Interestingly, HA is a highly conserved glycosaminoglycan component of the extracellular matrix that is degraded in the liver by the sinusoidal ECs and associated with inflammatory wound healing conditions, including hepatic clotting and fibrosis [ 4 , 32 ]. The significant association of HA with VOD/SOS by day 7 in this study suggests that it is a strong predictor of liver injury and endothelial dysfunction following HCT conditioning, which is consistent with previous findings [ 17 ].…”

Minor histocompatibility antigens HA‐8 and PANE1 in the TUNISIAN population

“…Nevertheless, this mismatch could induce beneficial effects such as graft‐versus‐tumor (GvT) or leukemic (GvL) cells. Furthermore, in the case of HLA‐identical solid organ transplantation, this mismatch could induce graft rejection (Akatsuka et al, 2007; Falkenburg et al, 2003; Nagasawa, 2021).…”

“…Host (GvH) reactions and, in cases where the GvH reaction produces adverse clinical symptoms, which usually include symptomatic organ damage, it is considered to be Graft vs. Host Disease (GvHD) reaction (Ghimire et al, 2017; Nagasawa, 2021). The development of these immune reactions is generally due to the disparity between the donor and the recipient of the hematopoietic stem cell (HSCs) in the human leukocyte antigens (HLA) (Petersdorf, 2017a, 2017b).…”

Machine learning applications and challenges in graft-versus-host disease: a scoping review

“…However, further optimization and validation of these models are still needed. We argue that simultaneously taking clinical parameters, recently discovered genetic determinants [70][71][72], and proteomic biomarkers [73][74][75] into account have the most potential to enhance the performance of ML-based prediction models, especially if these variables are widely accessible in a clinical setting, which may be feasible given recent advances in proteogenomic technologies. Several articles have looked into the development of these multimodal AI solutions that capture the complexity of human health and disease both in oncology and outside it [76][77][78][79][80].…”