title: Decreased IDO activity and increased TTS expression break immune tolerance in patients with immune thrombocytopenia.
abstract: BACKGROUND
  Indoleamine 2,3-dioxygenase (IDO) can promote peripheral immune tolerance and control autoimmune responses through tryptophan catabolism. Tryptophanyl-tRNA synthetase (TTS) can protect T cells from IDO-mediated cell injury. Impaired IDO-mediated tryptophan catabolism has been observed in some autoimmune diseases.
  
  
  METHODS
  The concentrations of plasma kynurenine and tryptophan were detected by high-pressure liquid chromatography. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry.
  
  
  RESULTS
  Compared with healthy controls, the PBMCs of patients with immune thrombocytopenia (ITP) had significantly increased expressions of IDO and TTS, especially IDO. However, the plasma tryptophan concentration was significantly elevated, and kynurenine concentration was significantly reduced in ITP patients. In CD4(+) and CD8(+) T cells of the ITP patients, IDO expressions were significantly lower than those in healthy controls, but in CD19(+) and CD14(+) cells, IDO expression significantly increased. Conversely, TTS expressions in CD4(+) and CD8(+) T cells of the ITP patients were significantly higher than those in healthy controls, but there was no difference either in CD19(+) or CD14(+) cells.
  
  
  CONCLUSIONS
  These results suggest that the activity of IDO enzyme is insufficient in ITP patients. Increased TTS expressions from CD4(+) and CD8(+) T cells might link to a pathogenic mechanism involved in increasing survival of autoreactive T cells in ITP patients.
authors.affiliation: Haematology Oncology Centre, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, Shandong, 250012, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Min
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Zhu
authors.forename: Cheng-Shan
authors.initials: CS
authors.lastname: Guo
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Dong
authors.forename: Ping
authors.initials: P
authors.lastname: Qin
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Sun
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
mesh_terms: D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000096:biosynthesis; D001327:Autoimmune Diseases; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D013921:Thrombocytopenia / Q000276:immunology*; D014364:Tryptophan / Q000097:blood; D014369:Tryptophan-tRNA Ligase / Q000096:biosynthesis*
chemical_list: D018941:Antigens, CD19; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018950:Lipopolysaccharide Receptors; D007737:Kynurenine; D014364:Tryptophan; D014369:Tryptophan-tRNA Ligase