title: The effects of rhBMP-2 and Treg/Th17 functional disequilibrium in uremic patients with cardiovascular complication after maintenance hemodialysis.
abstract: OBJECTIVE
  We compared the correlation of regulatory T cell (Treg) and Th17 cell function disequilibrium with calcification in uremic patients on maintenance hemodialysis (MHD) with healthy controls, and investigated if their influence possibly increased the development and outcome of cardiovascular complications in uremic patients after MHD.
  
  
  METHODS
  The extent of coronary artery calcification was assessed by coronary artery calcification scoring (CACS) in uremic patients with and without adverse cardiovascular events after MHD (MHD group 1 vs. MHD group 2, respectively). Peripheral blood mononuclear cells were incubated with rhBMP-2 as positive control. The Treg/Th17 cell frequencies, Foxp3 ROR-gt mRNA expressions, and MIP 3α/CCL20 concentrations were measured.
  
  
  RESULTS
  The CACS score was significantly higher in MHD group 1 as compared group 2. In comparison with controls, rhBMP-2 upregulates Treg/Th17 functional disequilibrium in uremic patients, displayed higher Treg and Th17 frequencies, Foxp3 and ROR-gt expressions, and MIP3α/CCL20 concentrations. However, the up-regulations of Treg frequencies and Foxp3 expressions were significant in controls but not in MHD patients. It was also observed that Treg/Th17 functional disequilibrium was not only correlated with rhBMP-2 state but also consistent with the cardiovascular complications. Moreover, the CACS was negatively correlated with Treg cell frequencies but positively correlated with Th17 cell frequencies and MIP3a/CCL20 concentrations.
  
  
  CONCLUSIONS
  Function disequilibrium of Treg/Th17 was related to the degree of the rhBMP-2 state. Function disequilibrium of the Treg/Th17 might act synergistically with rhBMP-2 in the high incidence of immune-mediated cardiovascular complications after MHD.
authors.affiliation: Department of Endocrinology & Nephrology, the Chongqing Zhongshan Hospital, Chongqing, China. clioyoyo@163.com
authors.forename: Chen
authors.initials: C
authors.lastname: Danyan
authors.forename: Huang
authors.initials: H
authors.lastname: Xiaolong
authors.forename: Lu
authors.initials: L
authors.lastname: Song
authors.forename: Gan
authors.initials: G
authors.lastname: Hua
authors.forename: Tang
authors.initials: T
authors.lastname: Weixue
authors.forename: Liu
authors.initials: L
authors.lastname: Ke
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000378:metabolism; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D061330:Multidetector Computed Tomography; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D006435:Renal Dialysis / Q000009:adverse effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome; D014511:Uremia / Q000097:blood / Q000276:immunology / Q000628:therapy*; D061205:Vascular Calcification / Q000276:immunology*
chemical_list: C525718:BMP2 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; C108355:CCL20 protein, human; D054418:Chemokine CCL20; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D011994:Recombinant Proteins