title: Serum protein gamma-glutamyl hydrolase, Ig gamma-3 chain C region, and haptoglobin are associated with the syndromes of pulmonary tuberculosis in traditional Chinese medicine.
abstract: BACKGROUND
  Traditional Chinese Medicine (TCM) has been applied in treating tuberculosis (TB) based on the TCM syndromes with the effects of inhibiting Mycobacterium, strengthening the body immune system, and reducing the pulmonary toxicity. We used bioinformatic methods to study the clinical and pathological characteristics of pulmonary TB patients with TCM syndromes. Isobaric tags for relative and absolute quantification - coupled two dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS) methods were applied to screen differentially expressed serum proteins.
  
  
  METHODS
  Pulmonary TB cases were divided into four distinctive TCM syndromes: pulmonary Yin deficiency (PYD) syndrome, hyperactivity of fire due to Yin deficiency (HFYD) syndrome, deficiency of Qi and Yin (DQY) syndrome, and deficiency of Yin and Yang (DYY) syndrome. The serum samples from 214 pulmonary TB patients were collected, and the clinical and pathological data was analyzed by using iTRAQ-2DLC-MS/MS. Finally, the differentially expressed proteins were screened and tested by ELISA. Only 5 patients with DYY syndrome were recruited in 3 years, which were not enough for further research.
  
  
  RESULTS
  The DQY cases had higher erythrocyte sedimentation rate (ESR) compared to the PYD and HFYD cases (P=0.0178). 94.44% (12 PYD, 18 HFYD, and 4 DQY before anti-TB treatment) of 36 treated TB cases were transformed to PYD accompanied with the reduction of ESR and absorption of pulmonary lesions. A total of 39 differentially expressed proteins (ratios of >1.3 or <0.75) were found among the three TCM syndromes. Proteomic studies revealed that gamma-glutamyl hydrolase (GGH), Ig gamma-3 chain C region (IGHG3), and haptoglobin (HPT) were specifically over-expressed in PYD (P<0.01), HFYD (P<0.001), and DQY cases (P<0.01), respectively. Furthermore, GGH was significantly higher in PYD cases compared to the HFYD and DQY cases (P<0.01, P<0.001, respectively), whereas IGHG3 was significantly higher in HFYD cases than PYD and DQY cases (P<0.001, P<0.01, respectively).
  
  
  CONCLUSIONS
  The results suggest that TCM syndromes are significantly correlated with the pulmonary lesions and ESR. GGH was associated with folate metabolism in PYD cases, IGHG3 was linked to the control of Mycobacterium infection in HFYD patients, and HPT was involved in hypoxia in DQY patients. The present study provides new biological basis to understand the pathological changes and proteomic differences of TB syndromes.
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China. 11318038@zju.edu.cn.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Jiang
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China. knight_880102@163.com.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pneumology, The Sixth Hospital of Shaoxing, Shaoxing, Zhejiang, China. weililiang1981@163.com.
authors.forename: Li-Liang
authors.initials: LL
authors.lastname: Wei
authors.affiliation: Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang, China. yuxiaomei_1@hotmail.com.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Yu
authors.affiliation: Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang, China. shi-lee-ying@163.com.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Shi
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China. dandanxu1220@163.com.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Xu
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China. zlchen_m@163.com.
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Chen
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China. pingzepeng@126.com.
authors.forename: Ze-Peng
authors.initials: ZP
authors.lastname: Ping
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China. lijichen@zju.edu.cn.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001799:Blood Sedimentation; D015331:Cohort Studies; D005260:Female; D006242:Haptoglobins / Q000032:analysis*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008516:Medicine, Chinese Traditional; D008875:Middle Aged; D014397:Tuberculosis, Pulmonary / Q000097:blood*; D055815:Young Adult; D011623:gamma-Glutamyl Hydrolase / Q000097:blood*
chemical_list: D006242:Haptoglobins; D007074:Immunoglobulin G; D011623:gamma-Glutamyl Hydrolase