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J Clin Invest ; 134(2)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-37971879

RESUMEN

BACKGROUND: Accurate detection of graft-versus-host disease (GVHD) is a major challenge in the management of patients undergoing hematopoietic stem cell transplantation (HCT). Here, we demonstrated the use of circulating cell-free DNA (cfDNA) for detection of tissue turnover and chronic GVHD (cGVHD) in specific organs. METHODS: We established a cocktail of tissue-specific DNA methylation markers and used it to determine the concentration of cfDNA molecules derived from the liver, skin, lungs, colon, and specific immune cells in 101 patients undergoing HCT. RESULTS: Patients with active cGVHD showed elevated concentrations of cfDNA, as well as tissue-specific methylation markers that agreed with clinical scores. Strikingly, transplanted patients with no clinical symptoms had abnormally high levels of tissue-specific markers, suggesting hidden tissue turnover even in the absence of evident clinical pathology. An integrative model taking into account total cfDNA concentration, monocyte/macrophage cfDNA levels and alanine transaminase was able to correctly identify GVHD with a specificity of 86% and precision of 89% (AUC of 0.8). CONCLUSION: cfDNA markers can be used for the detection of cGVHD, opening a window into underlying tissue dynamics in patients that receive allogeneic stem cell transplants. FUNDING: This work was supported by grants from the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, The Israel Science Foundation, the Waldholtz/Pakula family, the Robert M. and Marilyn Sternberg Family Charitable Foundation and the Helmsley Charitable Trust (to YD).


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Ácidos Nucleicos Libres de Células , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Metilación de ADN , Ácidos Nucleicos Libres de Células/genética , Enfermedad Injerto contra Huésped/diagnóstico , Biomarcadores , Marcadores Genéticos , Enfermedad Crónica
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