Association of Interleukin-10 promoter polymorphisms with neurosyphilis.

Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. Increased production of IL-10 has been found in late syphilis, presumably creating favorable conditions for bacteria persistence. Single-nucleotide polymorphisms (SNPs) within the promoter of IL-10 gene have been found to influence IL-10 production. We investigated whether SNPs in the IL-10 gene promoter are associated with cerebrospinal fluid (CSF) levels of IL-10 and neurosyphilis. Polymorphisms in the gene for IL-10 (G→A mutation at the position -1084 and C→A mutation at the position -592) were sought in 35 patients with syphilis and 24 healthy volunteers. CSF examination (i.e. routine laboratory tests and IL-10 levels) was performed in all syphilis patients. Neurosyphilis was defined as reactive CSF VDRL test or CSF white blood cells⩾5/µL and CSF protein concentration⩾45mg/dL. Overall, 31% of patients with syphilis had neurosyphilis. CSF IL-10 levels were significantly higher in patients with neurosyphilis when compared to those with syphilis but not neurosyphilis. -1082 GG and -592 CC genotypes were significantly associated with higher CSF IL-10 levels. Moreover, these genotypes were found to be more frequent in individuals with neurosyphilis in comparison to those without neurosyphilis. Anti-inflammatory immune response seems to be important in pathogenesis of neurosyphilis. Our data suggest that host-related factors, such as SNPs of immune regulatory genes may influence the susceptibility to neurosyphilis.

Toll-like receptor polymorphisms are associated with increased neurosyphilis risk.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in toll-like receptors (TLR) 1, 2, and 6 impair cell signaling in response to spirochetal lipoproteins. We investigated whether common SNPs in TLR1, TLR2, or TLR6 were associated with laboratory- or clinically-defined neurosyphilis. METHODS: Polymorphisms in the genes for TLR1 (a T→G mutation at position 1805), TLR2 (a G→A mutation at position 2258), and TLR6 (a C→T mutation at position 745) were sought in 456 white patients with syphilis. Laboratory-defined neurosyphilis included a reactive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) test. Clinically-defined neurosyphilis included new vision or hearing loss. Controls had CSF white blood cells of 5/µL or less, nonreactive CSF-Venereal Disease Research Laboratory, and no vision or hearing loss. RESULTS: Overall, 26.2% of patients had laboratory-defined and 36.2% had clinically-defined neurosyphilis. Compared with controls, patients with any of the 3 SNPs were more likely to have laboratory-defined neurosyphilis. Those with TLR2 or TLR6 SNPs were more likely to have clinically-defined neurosyphilis. These associations were independent of serum rapid plasma reagin titer. CONCLUSIONS: A common TLR1 polymorphism is associated with an increased risk of laboratory-defined neurosyphilis, and common TLR2 and TLR6 polymorphisms are associated with an increased risk of both laboratory- and clinically-defined neurosyphilis. These data suggest that host factors impact the natural history of syphilis.

[Actual clinical and immunological problems of neurosyphilis and neurotuberculosis]. / Aktualne zagadnienia kliniczne i immunologiczne kily i gruzlicy ukladu nerwowego.

In the past neurosyphilis and tuberculosis of the nervous system were the basic clinical problems in neurology. The decrease of the incidence rate has changed the situation. However, in the last few years, especially in connection with HIV infection, the incidence has even started to increase. In Poland the epidemiological situation is not alarming, but there exists some concern connected with the epidemic of syphilis and tuberculosis in countries near the Polish eastern border. In the laboratory diagnosis of syphilis the highest specificity and sensitivity has the TPHA test. In the therapy till now the best results are obtained with megadoses of penicillin. Early diagnosis of tuberculous meningitis, what is the decisive factor for positive results of the treatment can be obtained by PCR technique for detection of DNA genome of mycobacterium. In the treatment the method of choice is the concomitant use of four antimycobacterial drugs. However, there exists the serious problem of often observed drug resistance of mycobacterium.