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Reduced IL-35 levels are associated with increased platelet aggregation and activation in patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

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Abstract

Acute graft-versus-host disease (aGVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that suppresses the immune response. This prospective study explored IL-35 plasma levels in 65 patients after HSCT. The results revealed that the peripheral blood of patients with grades III–IV aGVHD (23.46 ng/ml) had reduced IL-35 compared to transplanted patients with grades I–II aGVHD (40.26 ng/ml, p < 0.01) or patients without aGVHD (41.40 ng/ml, p < 0.05). Allografts, including granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cell (PBPC) and G-CSF-primed bone marrow (GBM), from 38 patients were analyzed for IL-35 levels with respect to aGVHD. The patients who received lower levels of IL-35 cells in the GBM (28.0 ng/ml, p = 0.551) or lower levels of IL-35 in PBPC (53.46 ng/ml, p = 0.03) exhibited a higher incidence of aGVHD. Patients with aGVHD have increased platelet aggregation. IL-35 was added to patient blood in vitro, and platelet aggregation was inhibited by IL-35 in a dose-dependent manner. The markers of platelet activation (CD62P/PAC-1) can also be inhibited by IL-35. The results indicate that IL-35 may affect the development of aGVHD by inhibiting platelet activation and aggregation. Our data suggests that IL-35 represents a potentially effective therapeutic agent against aGVHD after allo-HSCT.

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Acknowledgments

The authors thank the staff of the Peking University Institute of Hematology for compassionate and competent care of the patients. This work was supported by the National Science Foundation of China (grant no. 81070449), the National Science Foundation of China (grant no. 81270643), the Beijing Natural Science Foundation (grant no. 7132194), and the Beijing Natural Science Foundation (grant no. 7112139).

Ethical standards

All human studies have been approved by the Ethics Committee of Peking University People’s Hospital and have therefore been performed in accordance with the ethical standards laid down in the 1975 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Hematology, Peking University People’s Hospital, Peking University, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China

    Xiaohui Zhang, Yi Zhou, Lanping Xu, Wei Han, Huan Chen, Yuhong Chen, Haixia Fu, Shiyuan Zhou, Qianming Wang, Feier Feng, Xiaolu Zhu, Kaiyan Liu & Xiaojun Huang

  2. Department of Laboratory Medicine, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China

    Jingzhong Zhao

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  1. Xiaohui Zhang
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  2. Yi Zhou
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  3. Lanping Xu
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  4. Wei Han
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  5. Huan Chen
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Correspondence to Xiaohui Zhang or Xiaojun Huang.

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Xiaohui Zhang and Yi Zhou share the first authorship.

Xiaohui Zhang and Xiaojun Huang share the co-corresponding author.

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Zhang, X., Zhou, Y., Xu, L. et al. Reduced IL-35 levels are associated with increased platelet aggregation and activation in patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Ann Hematol 94, 837–845 (2015). https://doi.org/10.1007/s00277-014-2278-7

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