title: Post-therapeutic recovery of serum interleukin-35 level might predict positive response to immunosuppressive therapy in pediatric aplastic anemia.
abstract: BACKGROUND
  The predictive value of interleukin-35 (IL-35) on efficacy of immunosuppressive therapy (IST) in aplastic anemia (AA) has not been well investigated. The aim of the study was to evaluate the association between serum IL-35 level and response to IST in pediatric AA.
  
  
  METHODS
  A total of 154 children with AA and 154 controls were included between January 2012 and December 2013. Blood and bone marrow fluid specimens were collected. Serum level of IL-35 was determined by enzyme-linked immunosorbent assay. Patients were treated with IST, and response to therapy was evaluated during 180-day follow-up period after starting therapy.
  
  
  RESULTS
  Serum levels of IL-35 at admission decreased significantly in patients compared with that in controls (10.9 ± 5.5 pg ml-1and 45.3 ± 8.8 pg ml-1, p < 0.001). After starting IST, serum levels of IL-35 in patients recovered 30.7 ± 9.7 pg ml-1in the first 28 days (p < 0.001). During the follow-up period, increased range of serum IL-35 level ≥30.7 pg ml-1in the first 28 days was associated with effective response to therapy (odds ratio 7.97, 95% confidence interval 3.82-16.79). In addition, Fas/FasL protein expression in bone marrow mononuclear cells dropped significantly in the same group of patients in the first 28 days (p < 0.05).
  
  
  CONCLUSIONS
  The study revealed that post-therapeutic recovery of circulating IL-35 concentration might be an independent predictor for effective response to IST in pediatric AA. Moreover, apoptosis might be involved in such a forecasting process.
authors.affiliation: a Department of Hematology, Yuying Children's Hospital , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: b Department of Hepatobiliary Surgery , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Tong
authors.affiliation: a Department of Hematology, Yuying Children's Hospital , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Department of Hematology, Yuying Children's Hospital , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhou
authors.affiliation: a Department of Hematology, Yuying Children's Hospital , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
authors.forename: Jiangchao
authors.initials: J
authors.lastname: Qian
authors.affiliation: a Department of Hematology, Yuying Children's Hospital , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
authors.forename: Juxiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Department of Hematology, Yuying Children's Hospital , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
authors.forename: Jichen
authors.initials: J
authors.lastname: Ruan
mesh_terms: D000741:Anemia, Aplastic / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007378:Interleukins / Q000097:blood*; D018655:Lymphocyte Count; D008297:Male; D011379:Prognosis; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D007378:Interleukins; C532417:interleukin-35, human
keywords: Aplastic anemia; apoptosis; immunosuppressive therapy; interleukin-35; response