title: 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.
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.
authors.affiliation: Institute of Hematology, Peking University People's Hospital, Peking University, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China, zhangxh100@sina.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Lanping
authors.initials: L
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Haixia
authors.initials: H
authors.lastname: Fu
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Zhou
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Zhao
authors.forename: Qianming
authors.initials: Q
authors.lastname: Wang
authors.forename: Feier
authors.initials: F
authors.lastname: Feng
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhu
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Liu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000502:physiology*; D011446:Prospective Studies; D014184:Transplantation, Homologous / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D007378:Interleukins; C532417:interleukin-35, human