Serum Thioredoxin at Allogeneic Hematopoietic Cell Transplantation Predicts Acute Gvhd

Thioredoxin (TXN) is a component of major reductive system in various eukaryotes. The TXN system maintains cellular homeostasis through anti-oxidative defense with its disulfide reductase activity against reactive oxygen species . Although oxidative stress is also considered to contribute to development of acute graft-versus-host disease (GVHD), clinical significance of TXN remains to be elucidated. The current study investigated the impact of TXN on the incidence of acute GVHD. The study included 89 patients who had undergone their first allogeneic hematopoietic transplantation (allo-HCT) between March 2022 and May 2024, and their serum samples at day 0 were sequentially collected (training cohort). The study also assessed 47 patients who had undergone their first allo-HCT between December 2012 and July 2015 and whose serum at around day 0 had previously been cryopreserved and available (validation cohort). Serum TXN was measured with enzyme-linked immunosorbent assay. According to the cut-off of TXN defined with the receiver operating characteristics (ROC) curve for grade II-IV acute GVHD, the high-TXN group demonstrated a significantly lower incidence of grade II-IV acute GVHD (100-day incidence: 41.5% vs 57.5%, P = 0.03, Figure). The impact of TXN was also confirmed in the validation cohort. Furthermore, the addition of TXN improved the predictive potential of clinical factor-based model for grade II-IV acute GVHD in the whole cohort (area under the curve of ROC: 0.666 vs 0 596, P = 0.07). TXN at day 0 of allo-HCT was significantly associated with a decreased risk of grade II-IV acute GVHD. Moreover, TXN had a weakly positive correlation with inflammatory cytokines such as tumor necrosis factor alfa and soluble CD40L , which suggested that TXN might elevate as a reaction to suppress the inflammatory state. TXN might play a role to ameliorate early phase of acute GVHD, and could be a useful biomarker for acute GVHD before the onset and contribute to establishing a prediction model.