1980s: ????

1
????????????
??? ????????
2
??????????
1980s ???? 1990s ???? 2000s ????????? 2012
429,677 ? ???? 12,477?
(???) 20?????????200?,???????6000?
Source China CDC
3
?????????????
4
2010???????????1300?
5
???????

• ?????????????????(40)
• ????????????????,
• ?????????20???????????????
• ???????????????

6
Humoral and cellular responses can be induced
after T.Pallidum infection.
7
??????????
??????? ???????????? ????????????????????,??????(?
????, stealth pathogen) ?????-?????(??????????????
),????,??? ???????,??????????????(??????)????,
????,?????,???????????????? ????????,?????1,5
Mb???15?,?????????,?????????
8
Molecular structure of T. pallidum envelope
structure
BamA analogue
Pore-forming lipoprotein
?????????????????,???????????????
OM?????,?????????????,?????????????????????????
OM??TprK, TP0136???????
Cox et al INFECTION AND IMMUNITY, Dec. 2010, p.
51785194
9
??????????
???????????????????? ????-????????,
??????????,T????IV????? ?????????T????,??????????
??,??????? ? IV????????????????,?? 1/3 ?????,1/3
???????,??????,??????????,????????,?????
10
??????? ? ??????,?????????????,??????????????,???
?, ???????????????,????????? (????) ???????,2?????
??????????????, ??????????????????????2???? ??????
????????????????????T????????, ???????????????????
???(??????) ???????,?? (VDRL, ????,?????,
????),?????-------2 ?????
11
Humoral and cellular responses can be induced
after T.Pallidum infection.
12
Treg
T.pallidum antigen TpF1 can promote the
differentiation of Treg.
Babolin C et al. J I mmunol.2011.1871377-1384.
13
Tregs

• Immune escape of pathogens

• Avoid the immune damage

14
Part ? Treg frequency and function in syphilis
patients without neurological involvement

Part ? Treg in Blood and Cerebrospinal Fluid of
neurosyphilis Patients
15
Part ? Treg frequency and function in syphilis
patients without neurological involvement

Part ? Treg in Blood and Cerebrospinal Fluid of
neurosyphilis Patients
16
100 healthy donors 71 patients with primary
syphilis, 136 patients with secondary
syphilis, 127 patients with latent syphilis,
97 patients with serofast syphilis 100
Neurosyphilis (52 asymptomatic Neurosyphilis
10 Meningealneurosyphilis 34General paresis
4 Tabes dorsalis )
17
Treg Numbers Are Elevated in the Peripheral Blood
of Syphilis Patients
18
Treg Suppressive Function Are Increased in
Secondary and Serofast Syphilis Patients
19
Serum TGF-ß
Positive correlation between Treg and TGF-ß
20
Association of circulating Treg numbers with
serum RPR titers of syphilis patients.
21
Conclusion

• Treg Numbers Are Elevated in the Peripheral
  Blood of Primary, Secondary, Latent and Serofast
  Syphilis Patients

• Treg Suppressive Function Are Increased in the
  Peripheral Blood of Secondary and Serofast
  Syphilis Patients

• Serum RPR Titers Are Positively Correlated to
  Treg
• Frequencies in Secondary, Latent and Serofast
  Syphilis

22
Part ? Treg frequency and function in syphilis
patients without neurological involvement

Part ? Treg in Blood and Cerebrospinal Fluid of
neurosyphilis Patients
23
Treg frequency in peripheral blood of
neurosyphilis patients
24
Analysis of CD4 CD25high Tregs in CSF
25
The laboratary fetures in CSF derived from
different types of syphilis patients
Type Type Non-neurosyphilis Asymptomatic Meningeal Parenchymal
Leukocytes Cells/µL 41 1432a 3515ab 164ac
CD4 d 29.72.4 41.82.3a 49.72.6 46.42.1a
CD4 CD25high e 22.01.0 20.01.1 12.51.4ab 12.01.2ab
CD4 CD25high Cells/µL 0.10.1 1.20.2a 0.90.3a 0.50.1ab
TGF-ß ng/ml 8.21.7 10.72.0 3.40.9ab 2.80.5ab
NOTE. a v.s. syphilis patients without
neurological involvement b v.s. asymptomatic
neurosyphilis patients c v.s. meningeal
neurosyphilis patients d percentage () among
CD45 leukocytes e percentage () among CD4 T
cells.
26
Conclusion

• Circulating Treg Numbers Are Higher in
  Neurosyphilis Patients than Syphilis Patients
  without Neurological Involvement

• CD4 T Cells Predominates in the Cerebrospinal
  Fluid of Neurosyphilis Patients

• CSF Treg Numbers Are Reduced in Symptomatic
  Neurosyphilis Patients

27
Treg
T.pallidum antigen TpF1 can promote the
differentiation of Treg.
Babolin C et al. J I mmunol.2011.1871377-1384.
28
Increased Interleukin-17 Correlates With Disease
Progression of Neurosyphilis
Results
Methods

• Th17 in peripheral blood from 69 syphilis
  patients without neurological involvement, 103
  neurosyphilis patients and 70 healthy donors were
  analyzed by flow cytometry.
• The level of IL-17 in cerebrospinal fluid was
  quantified by ELISA.
• One-year follow up for 44 neurosyphilis patients
  was further monitored to investigate the role of
  Th17/IL-17 in neurosyphilis.

Conclusions

• Th17 response may be involved in central nervous
  system damage and the associated clinical
  symptoms in neurosyphilis patients.
• Th17/IL-17 may be used as an alternative
  surrogate marker for assessing the efficacy of
  clinical treatment of neurosyphilis patients.

29
Increased Interleukin-17 Correlates With Disease
Progression of Neurosyphilis
Results
Methods

• Th17 in peripheral blood from 69 syphilis
  patients without neurological involvement, 103
  neurosyphilis patients and 70 healthy donors were
  analyzed by flow cytometry.
• The level of IL-17 in cerebrospinal fluid was
  quantified by ELISA.
• One-year follow up for 44 neurosyphilis patients
  was further monitored to investigate the role of
  Th17/IL-17 in neurosyphilis.

Conclusions

• Th17 response may be involved in central nervous
  system damage and the associated clinical
  symptoms in neurosyphilis patients.
• Th17/IL-17 may be used as an alternative
  surrogate marker for assessing the efficacy of
  clinical treatment of neurosyphilis patients.

30
Thanks
Dr. Haikong Lu Dr. Xin Gu Dr.Mei
Shi Dr.Gaoyin Dr. Zhifang Guan Dr. Weimin
Gong Dr. Yihong Qian Dr. Zhe Cai
Cuini Wang Ph.D. Kang Li M.S Ling Zhu Li
M.S Shufang Zhang M.S Zixiao Gao M.S
31
Thank You!
Pingyu Zhou, M.D., Ph.D.
zhoupingyu_at_medmail.com.cn