title: Sphingolipids as new biomarkers for assessment of delayed-type hypersensitivity and response to triptolide.
abstract: BACKGROUND
  Hypersensitivity diseases are associated with many severe human illnesses, including leprosy and tuberculosis. Emerging evidence suggests that the pathogenesis and pathological mechanisms of treating these diseases may be attributable to sphingolipid metabolism.
  
  
  METHODS
  High performance liquid chromatography-tandem mass spectrometry was employed to target and measure 43 core sphingolipids in the plasma, kidneys, livers and spleens of BALB/c mice from four experimental groups: control, delayed-type hypersensitivity (DTH) model, DTH+triptolide, and control+triptolide. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify potential biomarkers associated with variance between groups. Relationships between the identified biomarkers and disease markers were evaluated by Spearman correlation.
  
  
  RESULTS
  As a treatment to hypersensitivity disease, triptolide significantly inhibit the ear swelling and recover the reduction of splenic index caused by DTH. The sphingolipidomic result revealed marked alterations in sphingolipid levels between groups that were associated with the effects of the disease and triptolide treatment. Based on this data, 23 potential biomarkers were identified by OPLS-DA, and seven of these biomarkers correlated markedly with the disease markers (p<0.05) by Spearman correlation.
  
  
  CONCLUSIONS
  These data indicate that differences in sphingolipid levels in plasma and tissues are related to DTH and treatment with triptolide. Restoration of proper sphingolipid levels may attribute to the therapeutic effect of triptolide treatment. Furthermore, these findings demonstrate that targeted sphingolipidomic analysis followed by multivariate analysis presents a novel strategy for the identification of biomarkers in biological samples.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qu
authors.forename: Cai-Sheng
authors.initials: CS
authors.lastname: Wu
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Hou
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004139:Dinitrofluorobenzene / Q000009:adverse effects; D018450:Disease Progression; D004224:Diterpenes / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004423:Ear / Q000473:pathology; D004852:Epoxy Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006968:Hypersensitivity, Delayed / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010616:Phenanthrenes / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D013107:Sphingolipids / Q000097:blood / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D013107:Sphingolipids; C001899:triptolide; D004139:Dinitrofluorobenzene