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]: 8.77 ng/ml [4.76–19.13]) and serum (52.58 ng/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 6.63 ng/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.