title: Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis.
abstract: The potential mechanisms for altered matrix metalloproteinase (MMP) or tissue inhibitors of matrix metalloproteinase (TIMP) function in patients with syphilis and HIV-1 co-infection (HIV-S) was unclear. To determine the expression of MMP-2, 9 and TIMP-1, 2, 4 in the serum and cerebrospinal fluid (CSF) of HIV-S patients, a total of 20 HIV-S patients and 8 controls were enrolled in a HIV-1 clinical cohort for diagnosis of neurosyphilis in Taiwan. 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 270 cells/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.
authors.affiliation: Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Hung-Chin
authors.initials: HC
authors.lastname: Tsai
authors.forename: Shin-Yu
authors.initials: SY
authors.lastname: Ye
authors.forename: Calvin M
authors.initials: CM
authors.lastname: Kunin
authors.forename: Susan Shin-Jung
authors.initials: SS
authors.lastname: Lee
authors.forename: Shue-Ren
authors.initials: SR
authors.lastname: Wann
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
authors.forename: Min-Hong
authors.initials: MH
authors.lastname: Shi
authors.forename: Yung-Ching
authors.initials: YC
authors.lastname: Liu
authors.forename: Yao-Shen
authors.initials: YS
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008875:Middle Aged; D009494:Neurosyphilis / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D013587:Syphilis / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D013624:Taiwan; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases