ArticleFrontiers in immunology2026
Infection-associated sTNFR1 elevation predicts post-transplant thrombotic microangiopathy in severe aplastic anemia.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe and potentially fatal complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early identification of patients at risk is essential for timely intervention and improved outcomes. This study aimed to identify biomarkers capable of predicting the early risk of TA-TMA in patients with severe aplastic anemia (SAA) undergoing allo-HSCT. Methods: In a prospective nested case-control study of patients with SAA undergoing allo-HSCT, blood samples were collected before pretreatment, before infusion, and on days +7, +14, and +28. TA-TMA cases were matched 1:2 to controls. Biomarkers were compared, and predictive performance was assessed using Receiver operating characteristic analysis and Cox models. Results: TA-TMA was associated with markedly higher mortality (59% vs. 1.3%). Soluble tumor necrosis factor receptor 1 (sTNFR1) consistently showed the strongest predictive ability, including before pretreatment (area under the curve 0.76; 95% CI, 0.60-0.91). A cutoff of 1.93 ng/mL yielded 0.88 specificity and 0.69 sensitivity. Elevated pretreatment sTNFR1 (≥1.93 ng/mL) predicted TA-TMA (hazard ratio, 6.78; 95% CI, 2.26-20.3; p < 0.001) and death (21.44; 95% CI, 2.57-179; p = 0.005). 19 had pre-transplant infections, of whom 11 (58%) developed TA-TMA versus 6 of 32 (19%) without infection. Infected patients also showed higher pretreatment sTNFR1 levels (1.93 vs. 1.64 ng/ml, p = 0.0034). Conclusions: Pretreatment sTNFR1 is a strong early predictor of TA-TMA and mortality in patients with SAA undergoing allo-HSCT, suggesting Tumor Necrosis Factor-alpha-driven inflammation precedes clinical onset. sTNFR1 may be a useful early-warning biomarker, and infection control before transplantation may reduce risk.
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