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Plasma levels of complement activation fragments C3b and sC5b-9 significantly increased in patients with thrombotic microangiopathy after allogeneic stem cell transplantation

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Abstract

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an uncommon but severe complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). However, the mechanism is unclear. From 2011 to 2014, 20 patients with TA-TMA, 20 patients without, and 54 patients with various other complications, including veno occlusive disease (VOD), graft-versus-host disease (GVHD), and infection, were recruited in the study. Plasma vWF antigen (vWFAg), vWF activity (vWFAc), and ADAMTS13 activity were determined in these patients by ELISAs and FRETS-vWF73 assay, respectively. Plasma C3b, sC5b-9, and CH50 were also determined by ELISAs. Plasma levels of C3b were significantly increased in patients with either TA-TMA (p < 0.0001) or GVHD (p < 0.01). Plasma sC5b-9 and CH50 levels in patients with TA-TMA were also significantly increased (p < 0.001). Plasma ADAMTS13 activity was lower in patients with VOD, but normal with other complications. Both plasma vWFAg and vWFAc levels were not elevated in patients with TA-TMA or VOD compared with those of other groups. Complement activation likely via an alternative pathway (increased C3b, sC5b-9, and CH50) may play a role in the pathogenesis of TA-TMA. ADAMTS13 activity is reduced in VOD, but the ADAMTS13/vWF axis appears to be unaffected in patients with TA-TMA.

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Acknowledgments

This work was supported by grants from the Jiangsu Province of China (BE2016665, ZDRCA2016047 and RC2011105), National Nature Science Foundation of China (81270591 and 81670132), Jiangsu Provincial Special Program of Social Development (SBE2016740635), Jiangsu Provincial Special Program of Medical Science (BL2012005), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and NIH R01HL115187-01A1 (to XLZ).

Author contributions

YH and DW conceived and designed the study. JQ, JC, and JW performed the experiments. YT, JS, XM, and FC collected the clinical data. JC and JQ wrote the paper. XLZ, XW, ZW, and CR reviewed and edited the manuscript. All authors read and approved the manuscript.

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  1. Jiaqian Qi, Jie Wang, and Jia Chen contributed equally

Authors and Affiliations

  1. The First Affiliated Hospital of Soochow University, Jiangsu Institute of Haematology, Suzhou, China

    Jiaqian Qi, Jie Wang, Jia Chen, Jian Su, Yaqiong Tang, Xiaojin Wu, Xiao Ma, Feng Chen, Changgeng Ruan, Depei Wu & Yue Han

  2. Soochow University, Collaborative Innovation Centre of Haematology, Suzhou, China

    Jiaqian Qi, Jie Wang, Jia Chen, Jian Su, Yaqiong Tang, Xiaojin Wu, Xiao Ma, Feng Chen, Changgeng Ruan, Depei Wu & Yue Han

  3. Key Laboratory of Thrombosis and Haemostasis of Ministry of Health, Suzhou, China

    Jiaqian Qi, Jie Wang, Jia Chen, Jian Su, Yaqiong Tang, Xiaojin Wu, Xiao Ma, Feng Chen, Changgeng Ruan, Depei Wu & Yue Han

  4. Divsion of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, 35243, USA

    X. Long Zheng

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  1. Jiaqian Qi
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Correspondence to Depei Wu or Yue Han.

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All the patients provided written informed consent for the protocol, which was approved by our hospital’s Ethics Committee.

Conflict of interest

XLZ is a member of the speakers’ bureau and has received research support from Alexion and served as a consultant for Ablynx. All other authors declare no conflict of interest.

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Qi, J., Wang, J., Chen, J. et al. Plasma levels of complement activation fragments C3b and sC5b-9 significantly increased in patients with thrombotic microangiopathy after allogeneic stem cell transplantation. Ann Hematol 96, 1849–1855 (2017). https://doi.org/10.1007/s00277-017-3092-9

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