TY - JOUR
T1 - Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis
AU - Tsai, Hung Chin
AU - Ye, Shin Yu
AU - Kunin, Calvin M.
AU - Lee, Susan Shin Jung
AU - Wann, Shue Ren
AU - Tai, Ming Hong
AU - Shi, Min Hong
AU - Liu, Yung Ching
AU - Chen, Yao Shen
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - Acquire immunodeficiency syndrome
KW - Matrix metalloproteinase
KW - Meningitis
KW - Syphilis
KW - Tissue inhibitors of matrix metalloproteinase
UR - http://www.scopus.com/inward/record.url?scp=79953050566&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953050566&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2011.02.007
DO - 10.1016/j.cyto.2011.02.007
M3 - Article
C2 - 21354815
AN - SCOPUS:79953050566
SN - 1043-4666
VL - 54
SP - 109
EP - 116
JO - Cytokine
JF - Cytokine
IS - 2
ER -
