BACKGROUND: Hematopoietic stem cell transplantation (HSCT) can cause serious transplant-related complications such as graft-versus-host disease (GVHD). Acute GVHD (aGVHD) has been diagnosed by clinical manifestations, laboratory data and pathological effects until now, but recently the discovery of specific biomarkers such as suppression of tumorigenicity 2 (ST2), elafin and regenerating islet-derived 3α (REG3α) is challenging this approach. METHODS: We investigated the expression of aGVHD-related markers (regulated on activation normal T-cell expressed and secretes: RANTES, elafin, REG3α and ST2) and endothelial cell activation markers (soluble vascular cell adhesion molecule: sVCAM-1 and plasminogen activator inhibitor: PAI-1) in patients undergoing allogeneic HSCT. Additionally, we studied the effects of recombinant soluble thrombomodulin (rTM) on the expression of these markers. Our study cohort included 225 patients who underwent allogeneic HSCT at several institutions in Japan. RESULTS: RANTES, sVCAM-1, PAI-1, elafin, REG3α and ST2 exhibited significant increases in patients not receiving rTM after HSCT. When we examined patients with confirmed complications, the frequencies of aGVHD and VOD were significantly lower in the rTM-treated group. In addition, aGVHD-related biomarkers such as elafin, REG3α, and ST2 were elevated significantly in patients with aGVHD. CONCLUSION: Our findings suggest that endothelial cell activation might be linked to aGVHD, and that rTM might act to prevent aGVHD, at least in part, through its effect on endothelial cells.
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) can cause serious transplant-related complications such as graft-versus-host disease (GVHD). Acute GVHD (aGVHD) has been diagnosed by clinical manifestations, laboratory data and pathological effects until now, but recently the discovery of specific biomarkers such as suppression of tumorigenicity 2 (ST2), elafin and regenerating islet-derived 3α (REG3α) is challenging this approach. METHODS: We investigated the expression of aGVHD-related markers (regulated on activation normal T-cell expressed and secretes: RANTES, elafin, REG3α and ST2) and endothelial cell activation markers (soluble vascular cell adhesion molecule: sVCAM-1 and plasminogen activator inhibitor: PAI-1) in patients undergoing allogeneic HSCT. Additionally, we studied the effects of recombinant soluble thrombomodulin (rTM) on the expression of these markers. Our study cohort included 225 patients who underwent allogeneic HSCT at several institutions in Japan. RESULTS:RANTES, sVCAM-1, PAI-1, elafin, REG3α and ST2 exhibited significant increases in patients not receiving rTM after HSCT. When we examined patients with confirmed complications, the frequencies of aGVHD and VOD were significantly lower in the rTM-treated group. In addition, aGVHD-related biomarkers such as elafin, REG3α, and ST2 were elevated significantly in patients with aGVHD. CONCLUSION: Our findings suggest that endothelial cell activation might be linked to aGVHD, and that rTM might act to prevent aGVHD, at least in part, through its effect on endothelial cells.
Authors: Sarah A Wall; Qiuhong Zhao; Martha Yearsley; Luke Blower; Akwasi Agyeman; Parvathi Ranganathan; Shangbin Yang; Haiwa Wu; Matthew Bostic; Samantha Jaglowski; Jonathan E Brammer; Basem William; Hannah Choe; Alice S Mims; Sam Penza; Yvonne Efebera; Steven Devine; Spero Cataland; Stella M Davies; Sumithira Vasu Journal: Blood Adv Date: 2018-10-23
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Authors: Laura Solán; Mi Kwon; Diego Carbonell; Nieves Dorado; Pascual Balsalobre; David Serrano; María Chicano-Lavilla; Javier Anguita; Jorge Gayoso; José Luis Díez-Martín; Carolina Martínez-Laperche; Ismael Buño Journal: Front Immunol Date: 2019-10-09 Impact factor: 7.561
Authors: Adrienne M Dorrance; Moutuaata M Moutuou; Chinmayee Goda; Natalie E Sell; Sonu Kalyan; Malith Karunasiri; Rohan Kulkarni; Marie Goulard; Sofia Kolovich; Alexander Rudich; Eric Naumann; Antoine Ackaoui; Charles-Etienne Bigras; Francis Daudelin; Ramiro Garzon; Parvathi Ranganathan; Martin Guimond Journal: Blood Adv Date: 2022-04-12