Objective: To test whether the tryptophan metabolism was abnormal in newly diagnosed ITP patients as well as in these patients after treatment with dexamethasone. Methods: Newly diagnosed patients with ITP between Jan 2014 and May 2015 were enrolled, including 14 females and 11 males, with a median age of 57 years and a median PLT count of 16 (0-32) ×10(9)/L. All patients were treated with oral dexamethasone. The expression levels of IDO mRNA and TTS mRNA in peripheral blood mononuclear cells (PBMC) were analyzed by real-time quantitative polymerase chain reaction. ELISA was used to test the concentrations of IDO and TTS in serum. The concentrations of plasma kynurenine and tryptophan were detected by high-pressure liquid chromatography. Samples from healthy individuals were tested as controls. Results: ①After dexamethasone treatment, 17 patients resulted in persistent remission, 2 cases were ineffective, and relapse occurred in 6 cases at a median follow-up of 11 (6-18) months. ②Before and after dexamethasone treatment, the relative expression of indoleamine2,3-dioxygenase (IDO) mRNA and tryptophanyl t-RNA synthetase (TTS) mRNA showed that there were significant decline in persistent remission group (2.54±0.86 vs 19.85±5.36, t=3.188, P=0.003; 0.68±0.19 vs 45.39±15.83, t=2.842, P=0.008) , compared with the normal control group, the difference was not statistically significant (t=2.313, P=0.027; t=1.127, P=0.268) . After treatment, the IDO concentration decreased [ (19.34±0.42) U/ml] and the TTS concentration was markedly increased [ (13.37±0.54) μg/L] in sustained remission group compared with that before treatment [ (21.91±0.37) U/ml] as well as that in normal controls. In particularly, abnormal tryptophan catabolism could be recovered in these 17 patients with persistent remission [Try: (19.85±5.36) μmol/L vs (19.65±4.55) μmol/L, t=1.027, P=0.311; Kyn: (0.56±0.26) μmol/L vs (0.58±0.23) μmol/L, t=2.075, P=0.448]. ③There was no obviously difference in the relative expression of IDO mRNA and TTS mRNA, the concentration of IDO and TTS and the abnormal tryptophan catabolism between before and after treatment of dexamethasone in patients without response and relapsed patients (all P>0.01) . Conclusion: The tryptophan catabolism was abnormal in ITP patients, and it could be recovered in patients with persistent remission.
目的：研究原发免疫性血小板减少症（ITP）患者大剂量地塞米松治疗前后色氨酸代谢状态。方法： 2014年1月1日至2015年5月31日期间25例新诊断ITP患者纳入研究，男11例、女14例，中位年龄57（27~87）岁，初诊时中位PLT为16（0~32）×10(9)/L。治疗方案：地塞米松40 mg/d×4 d，口服。治疗前后，采用实时定量PCR检测外周血单个核细胞（PBMC）内吲哚胺-2,3-双加氧酶（IDO）、色氨酰t-RNA合成酶（TTS）基因mRNA表达，ELISA法检测血清IDO、TTS浓度，高效液相色谱分析法（HPLC）检测血清色氨酸、犬尿氨酸浓度。以25名健康志愿者为正常对照组。结果： ①在中位随访时间11（6~18）个月内，17例患者获得持续缓解（完全反应16例、有效1例），2例无效，6例复发。将患者按疗效分为持续缓解组（17例）和无效/复发组（8例）。②持续缓解组（17例）患者治疗后PBMC中IDO、TTS基因mRNA相对表达量均低于治疗前（2.54±0.86对19.85±5.36，t=3.188，P=0.003；0.68±0.19对45.39±15.83，t=2.842，P=0.008），与正常对照组比较差异无统计学意义（t=2.313，P=0.027；t=1.127，P=0.268）。治疗前血清IDO[（21.91±0.37）U/ml]高于正常对照组（t=4.468，P<0.001），治疗后[（19.34±0.42）U/ml]与正常对照组比较差异无统计学意义（t=2.170，P=0.370）；治疗前血清TTS浓度[（9.14±0.22）μg/L]与正常对照组比较差异无统计学意义（t=1.220，P=0.229），治疗后[（13.37±0.54）μg/L]高于治疗前（t=7.302，P<0.001）。血清色氨酸浓度治疗后低于治疗前[（19.85±5.36）μmol/L对（54.72±6.50）μmol/L，t=19.551，P<0.001]，与正常对照组比较差异无统计学意义（t=1.027，P=0.311）；治疗后犬尿氨酸浓度高于治疗前[（0.56±0.26）μmol/L对（0.22±0.13）μmol/L，t=17.013，P<0.001]，与正常对照组比较差异无统计学意义（t=2.075，P=0.448）。③无效/复发组患者治疗前后IDO、TTS基因mRNA表达水平及血清IDO、TTS色氨酸、犬尿氨酸浓度差异均无统计学意义（P>0.01）。结论： ITP患者体内存在色氨酸代谢异常；大剂量地塞米松治疗后获得持续缓解患者体内色氨酸代谢异常得到纠正。.
Keywords: Immune thrombocytopenia; Indoleamine 2, 3 dioxygenase; Tryptophan; Tryptophanyl-tRNA synthetase.