Soluble T Cell Immunoglobulin and Mucin Domain-3 (sTIM-3) Predicts Graft-Versus-Host Disease (GVHD) in Iranian Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Background: T cell immunoglobulin and mucin domain-3 (TIM-3) is an immune-checkpoint molecule that is upregulated following allogeneic immune responses and could play an important role in the development and pathogenesis of graft-versus-host disease (GVHD). The soluble form of TIM-3 (sTIM-3) is increased following the upregulation of membranous TIM-3. Objectives: The aim of this study was to evaluate the association between plasma level of sTIM-3 and acute GVHD (aGVHD) incidence in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Blood samples were collected from 42 allo-HSCT patients and 20 healthy individuals 2 weeks after allo-HSCT. The plasma level of sTIM-3 was measured using enzyme-linked immunosorbent assay (ELISA). The clinical and demographic data of patients were collected from the clinical documents. Data analysis was evaluated using student t-test and one-way ANOVA tests. P-values less than 0.05 were assumed statistically significant. Results: Among 18 (42.8%) patients with aGVHD symptoms, 10 (23.8%) had severe GVHD and 8 (19%) experienced mild GVHD. Plasma sTIM-3 levels at day +14 were significantly higher in patients who developed aGVHD compared to allo-HSCT patients without GVHD and also the healthy control individuals (P-value = 0.015 and < 0.001). Among the aGVHD patients, the sTIM-3 levels in those with severe GVHD were approximately 2.5 times higher than those with mild GVHD (P-value < 0.001). Conclusions: We have identified a high plasma level of sTIM-3 as a valuable biomarker in predicting the development of acute GVHD, especially severe aGVHD in allo-HSCT patients.