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

Hung Chin Tsai, Shin Yu Ye, Calvin M. Kunin, Susan Shin Jung Lee, Shue Ren Wann, Ming Hong Tai, Min Hong Shi, Yung Ching Liu, Yao Shen Chen

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish
Pages (from-to)109-116
Number of pages8
JournalCytokine
Volume54
Issue number2
DOIs
Publication statusPublished - May 2011

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Neurosyphilis
Cerebrospinal fluid
Syphilis
Matrix Metalloproteinases
HIV Infections
Cerebrospinal Fluid
HIV-1
Tissue
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Serum
HIV
Matrix Metalloproteinase 1
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Tissue Inhibitor of Metalloproteinases
Research laboratories
Sexually Transmitted Diseases
Reagins
Tissue Inhibitor of Metalloproteinase-2

Keywords

  • Acquire immunodeficiency syndrome
  • Matrix metalloproteinase
  • Meningitis
  • Syphilis
  • Tissue inhibitors of matrix metalloproteinase

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

Cite this

Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis. / Tsai, Hung Chin; Ye, Shin Yu; Kunin, Calvin M.; Lee, Susan Shin Jung; Wann, Shue Ren; Tai, Ming Hong; Shi, Min Hong; Liu, Yung Ching; Chen, Yao Shen.

In: Cytokine, Vol. 54, No. 2, 05.2011, p. 109-116.

Research output: Contribution to journalArticle

Tsai, Hung Chin ; Ye, Shin Yu ; Kunin, Calvin M. ; Lee, Susan Shin Jung ; Wann, Shue Ren ; Tai, Ming Hong ; Shi, Min Hong ; Liu, Yung Ching ; Chen, Yao Shen. / Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis. In: Cytokine. 2011 ; Vol. 54, No. 2. pp. 109-116.
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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 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.",
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