title: Increased Tim-3 expression on peripheral T lymphocyte subsets and association with higher disease activity in systemic lupus erythematosus.
abstract: BACKGROUND
  Both the T cell immunoglobulin domain- and mucin domain-containing molecule-3 (Tim-3) and the death receptor Fas contribute to the pathogenesis of various autoimmune diseases, including systemic lupus erythematosus (SLE). The aim of the present study was to determine whether Tim-3 and Fas are co-expressed on certain peripheral T lymphocyte subsets, and whether this expression is associated with greater disease activity in SLE.
  
  
  METHODS
  Peripheral blood mononuclear cells were isolated from 46 patients newly diagnosed with SLE and 28 age- and sex-matched healthy controls (HCs). Expression of Tim-3 and Fas on T subsets was analyzed by flow cytometry, while mRNA levels of the Tim-3 ligand galectin-9 and Fas ligand FasL were assayed using real-time RT-PCR.
  
  
  RESULTS
  The proportions of CD3(+)CD4(+) and CD3(+)CD4(-) T cells expressing Tim-3(+) and Tim(+)Fas(+) were significantly higher in patients than in HCs (p < 0.05), while the proportions of these subtypes expressing Fas were similar for the two groups. Patients with active SLE, as defined by their score on the SLE Disease Activity Index, had lower proportions of CD3(+)CD4(+) T cells and higher proportions of CD3(+)CD4(+)Tim-3(+) and CD3(+)CD4(+)Tim-3(+)Fas(+) T cells than did patients with stable SLE. Serum levels of complement C3 and C4 proteins, considered as a marker of SLE activity, correlated negatively with proportions of CD3(+)CD4(+) and CD3(+)CD4(-) T cells expressing Tim-3.
  
  
  CONCLUSIONS
  Expression of Tim-3 and co-expression of Tim-3 and Fas on certain peripheral T subsets are associated with disease activity in SLE patients. Future research should examine whether the same is true of other T subsets implicated in SLE, and should explore the potential role(s) of Tim-3 in the disease pathway.
  http://www.diagnosticpathology.diagnomx.eu/vs/1855527845145188.
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, China. rheum_888@163.com.
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Song
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, China. wangxiao.sdu@live.cn.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Ji'nan, 250012, China. drxupingwang@126.com.
authors.forename: Xu-ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: Cryomedicine Laboratory, Qilu Hospital of Shandong University, Ji'nan, 250012, China. drdongli@126.con.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, China. drding@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, China. drhuaxiangliu@126.com.
authors.forename: Hua-xiang
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, China. yuxiaohello@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, China. drxfuli@126.com.
authors.forename: Xing-fu
authors.initials: XF
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, China. drshuqiang@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D053222:Fas Ligand Protein / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D037161:Galectins / Q000235:genetics; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015854:Up-Regulation; D055815:Young Adult; D019014:fas Receptor / Q000097:blood
chemical_list: D015415:Biomarkers; C038245:C3 protein, human; D003176:Complement C3; D003181:Complement C4; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D019014:fas Receptor