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The effect of danger-associated molecular patterns on survival in acute graft versus host disease

Bone Marrow Transplantation volume 59, pages 189–195 (2024)Cite this article

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Abstract

Danger-associated molecular patterns (DAMPs) are molecules that can initiate and maintain robust inflammatory responses and were investigated in the pathogenesis of graft versus host disease (GvHD). Uric acid (UA) and fibrinogen (Fib) are DAMPs released from damaged tissue during allogeneic hematopoietic stem cell transplantation (allo-HCT) and GvHD. We aimed to evaluate the effects of UA and Fib levels on survival in GvHD. One hundred seventy-four patients with grade 2-4 acute GvHD were included. UA and Fib levels were evaluated on allo-HCT day 0 and GvHD on days 0, 7, 14, and 28. Fib GvHD day 0 was the independent predictor for overall survival (OS), non-relapse mortality (NRM), and progression-free survival in multivariable models (HR 0.98, p < 0.001; HR 0.98, p = 0.001, HR 0.98, p = 0.006, respectively). Also UA GvHD day 28 was the independent predictor for OS and NRM (HR 0.77, p = 0.004; HR 0.76, p = 0.011, respectively). Our results indicated that hypouricemia and hypofibrinogenemia were associated with a significantly shorter OS and higher NRM. UA and Fib are remarkable molecules in GvHD because they are routinely utilized, readily available, can be therapeutic targets, and have DAMPs and antioxidant features.

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Fig. 1: Endpoints results by fibrinogen level.
Fig. 2: Endpoints results by uric acid level.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. The Figshare DOI is https://doi.org/10.6084/m9.figshare.22302763.

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Acknowledgements

The authors thank all the patients who participated in this study and all the doctors, nurses, staff and patient relatives in the clinic for their hard work for the patients.

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Authors and Affiliations

  1. Department of Hematology, Faculty of Medicine, Kırıkkale University, Kırıkkale, Türkiye

    Serhat Çelik

  2. Department of Hematology, Faculty of Medicine, Medipol Mega University, İstanbul, Türkiye

    Leylagül Kaynar

  3. Department of Hematology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye

    Zeynep Tuğba Güven, Muzaffer Keklik & Ali Ünal

  4. Department of Internal Medicine, Faculty of Medicine, Erciyes University, Kayseri, Türkiye

    Kübra Atasever Duran

  5. Department of Pathology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye

    Olgun Kontaş

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Contributions

LK and SÇ designed the study, SÇ and ZTG performed the statistical analysis, LK and SÇ wrote the manuscript, KAD, SÇ, MK, and AÜ did the data managements and OK provided the pathological information. All authors reviewed and approved the final version of the manuscript. Each Author has contributed substantially to the research, preparation and production of the paper and approves of its submission to the Bone Marrow Transplantation.

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Correspondence to Serhat Çelik.

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The authors declare no competing interests.

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All patients signed written informed consent. All ethical procedures and standards were carried out following the 1975 Helsinki Declaration. The study was approved by Erciyes University Clinical Research Ethics Committee.

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Çelik, S., Kaynar, L., Güven, Z.T. et al. The effect of danger-associated molecular patterns on survival in acute graft versus host disease. Bone Marrow Transplant 59, 189–195 (2024). https://doi.org/10.1038/s41409-023-02145-7

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