Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Cytokine. 2011 May;54(2):109-16. doi: 10.1016/j.cyto.2011.02.007. Epub 2011 Feb 26.
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.
梅毒和 HIV-1 合并感染（HIV-S）患者基质金属蛋白酶（MMP）或基质金属蛋白酶抑制剂（TIMP）功能改变的潜在机制尚不清楚。为了确定 MMP-2、9 和 TIMP-1、2、4 在 HIV-S 患者血清和脑脊液（CSF）中的表达，我们共招募了 20 名 HIV-S 患者和 8 名对照者，他们来自于台湾的一个 HIV-1 临床队列，用于诊断神经梅毒。通过 ELISA 法测定 MMP-2、9 和 TIMP-1、2、4 的血清和 CSF 浓度。使用明胶酶谱法检测 CSF 中 MMP-2 和 MMP-9 的表达。神经梅毒的定义为 CSF 白细胞计数≥20 个/μL 或反应性 CSF 性病研究实验室（VDRL）。所有 HIV-S 患者均为男性。大多数（85%）有男男性行为（MSM），血清快速血浆反应素（RPR）滴度≥1:32。诊断梅毒时的中位年龄为 35 岁（IQR 30-43）。梅毒诊断时的中位 CD4 T 细胞计数为 270 个/μL（IQR 96-484）。10 名患者（50%）根据反应性 CSF VDRL 试验（n=8）或 CSF 白细胞计数增加≥20/μL（n=2）诊断为神经梅毒。与对照组相比，HIV-S 患者的 CSF MMP-9、TIMP-1 和 TIMP-2 浓度显著升高（P<0.05）。HIV-S 患者的 CSF TIMP-4 浓度明显低于对照组（452 pg/ml 比 3101 pg/ml），P<0.0001。两组血清浓度无显著差异。唯一能区分 HIV-1 患者有无神经梅毒的发现是 CSF MMP-9 表达显著升高。总之，无论是否符合神经梅毒的实验室定义，HIV-S 患者的 MMP/TIMP 系统均存在失调。CSF 中 MMP-9 水平是区分有或无神经梅毒的唯一指标。
