Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis

Serum and CSF concentrations of MMP-2, 9, and TIMP-1, 2, 4 were determined by ELISA. Gelatin zymography was used to detect the expression of MMP-2 and MMP-9 in the CSF. Neurosyphilis was defined as a CSF white blood cell count ⩾20 cells/μL or a reactive CSF Venereal Disease Research Laboratory (VDRL). All the patients with HIV-S were males. Most (85%) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ⩾1:32. The median age was 35 years (IQR 30-43). The median CD4 T cell counts at the time of the diagnosis of syphilis were 270cells/μL (IQR 96-484). Ten patients (50%) had neurosyphilis based on a reactive CSF VDRL test (n = 8) or increased CSF white cell counts ⩾20/μL (n = 2). The concentrations of CSF MMP-9, TIMP-1, and TIMP-2 were significantly higher in patients with HIV-S than the controls (P < 0.05). The CSF TIMP-4 concentrations were significantly lower in those with HIV-S (452 pg/ml) than controls (3101 pg/ml), P < 0001. There were no significant differences in serum concentrations between the groups. The only finding that distinguished HIV-1 patients with from those without neurosyphilis is a significant higher expression of CSF MMP-9. In conclusion, the MMP/TIMP system was found to be dysregulated in patients with HIV-S regardless of whether they met the laboratory definition of neurosyphilis. The CSF level of MMP-9 was the only measure that distinguished those with or without neurosyphilis.