title: Macrophage migration inhibitory factor as a novel cerebrospinal fluid marker for neurosyphilis among HIV-negative patients.
abstract: BACKGROUND
  Neurosyphilis (NS) is difficult to diagnose, especially in syphilis patients with negative cerebrospinal fluid (CSF) rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) tests.
  
  
  METHODS
  We conducted a cross-sectional study and an analysis of macrophage migration inhibitory factor (MIF) in syphilitic patients to identify a novel marker for the diagnosis of NS, with a focus on probable NS (NS with negative VDRL/RPR tests). For this purpose, CSF and serum MIF concentrations were determined in 43 NS and 43 syphilis/non-NS (N-NS) patients at the Zhongshan Hospital of the Medical College of Xiamen University from July 2014 to June 2015. Sixty-three blood donors were used as healthy controls.
  
  
  RESULTS
  NS patients had higher CSF (median [IQR]: 8.77ng/ml [4.76-19.13]) and serum (52.58ng/ml [28.31-95.94]) MIF concentrations than N-NS patients did (4.08 [2.21-9.68] and 34.30 [19.77-59.75], respectively). Using a cut-off point of 6.63ng/ml, CSF MIF had a sensitivity of 74.42% and a specificity of 67.74% for the diagnosis of NS. The sensitivity was higher than that of CSF RPR (39.53%) and increased protein (48.84%) tests and similar to that of CSF pleocytosis (67.44%). Additionally, the sensitivity of CSF MIF, which was 92.31% for the diagnosis of probable NS, was higher than that of CSF pleocytosis (65.38%) and increased protein (53.85%) tests. By integrating all CSF parameters (pleocytosis, increased protein and MIF), the sensitivity would be improved to 100% by parallel testing, which would avoid missed diagnoses. Moreover, the specificity would be improved to 100% by the serial testing algorithm, which would again avoid misdiagnosis.
  
  
  CONCLUSIONS
  CSF MIF concentrations can be used as a novel CSF marker to establish or exclude a diagnosis of NS.
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China; Xiamen Zhongshan Hospital, Fujian Medical University, Xiamen, China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Lin
authors.affiliation: Medical Technology Department of Fujian Health College, Fuzhou, China.
authors.forename: Dan-Hong
authors.initials: DH
authors.lastname: Lin
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Tong
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Liu
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Fan
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Xiao-Zhen
authors.initials: XZ
authors.lastname: Zhu
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Gao
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Chen
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Zheng
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: Xiamen Huli District Maternity and Child Care Hospital, Xiamen, China.
authors.forename: Shu-Lian
authors.initials: SL
authors.lastname: Li
authors.affiliation: Xiamen Huli District Maternity and Child Care Hospital, Xiamen, China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Lin
authors.affiliation: Xiamen Huli District Maternity and Child Care Hospital, Xiamen, China.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Lin
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China; Xiamen Zhongshan Hospital, Fujian Medical University, Xiamen, China. Electronic address: niujianjun211@xmu.edu.cn.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Niu
authors.affiliation: Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China; Xiamen Zhongshan Hospital, Fujian Medical University, Xiamen, China. Electronic address: yangtianci@xmu.edu.cn.
authors.forename: Tian-Ci
authors.initials: TC
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003430:Cross-Sectional Studies; D005260:Female; D018023:HIV Seronegativity; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009494:Neurosyphilis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008263:Macrophage Migration-Inhibitory Factors
keywords: Diagnosis; Macrophage migration inhibitory factor; Marker; Neurosyphilis; Treponema pallidum