HU Chao; CHEN Cao; CHEN Jia; XIAO Kang; ZHOU Wei; XIA Ying; YANG Wei; WANG Lin; SHI Qi; DONG Xiao Ping

doi:10.3967/bes2021.113

Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China

Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 420115, Hubei, China

College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163711, Heilongjiang, China

China Academy of Chinese Medical Sciences, Beijing 100700, China

Center for Global Public Health, Chinese Center for Disease Control and Prevention, Beijing 102206, China

Funds: This work was supported by National Natural Science Foundation of China [81772197, 81401670, 81630062]; National Key Research and Development Program of China [2018YFC1200305]; National Science and Technology Major Project of China [2018ZX10102001]; SKLID Development Grant [2019SKLID401, 2019SKLID603, 2016SKLID603]; and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018RC330004]

More Information

Author Bio:
HU Chao, male, born in 1992, PhD Candidate, majoring in immunology

CHEN Cao, male, born in 1983, PhD, majoring in immunology

Corresponding author: DONG Xiao Ping, Tel/Fax: 86-10-58900815, E-mail: dongxp238@sina.com

^&These authors contributed equally to this work.

Factors

Grouped

Positive rate (%)

Positive time post-reaction (h)

Peak ThT fluorescence units (rfu)

Positive no./
grouped no.

P-value

Median
(min, max)

P-value

Median
(min, max)

P-value

Age
(years)

< 50

13/35 (37.1)

0.376^a

8.64 (2.88, 53.40)

0.369^b

141,434
(30,882, 260,000)

0.455^b

50–70

22/74 (29.7)

7.56 (2.16, 21.60)

127,168
(52,188, 250,144)

> 70

1/8 (12.5)

20.16

62,818

Gender

Male

18/58 (31.0)

0.951^a

7.96 (2.88, 44.70)

0.254^c

116,813
(51,161, 245,791)

0.569^c

Female

18/59 (30.5)

5.76 (2.16, 53.40)

143,248
(30,882, 260,000)

Tau ELISA
(pg/mL)

< 1,400

16/58 (27.6)

0.460^a

6.12 (2.16, 44.70)

0.425^c

118,388
(51,161, 250,144)

0.340^c

≥ 1,400

20/59 (33.9)

8.00 (2.16, 53.40)

132,739
(30,882, 260,000)

14-3-3Western
blot

Positive

22/71 (31.0)

0.950^a

5.76 (2.16, 44.70)

0.172^c

126,029
(51,161, 260,000)

0.559^c

Negative

14/46 (30.4)

9.04 (2.16, 53.40)

127,168
(30,882, 223,636)

EEG

Positive

16/32 (50.0)

0.006^a

4.32 (2.16, 12.24)

0.005^c

151,876
(87,548, 260,000)

0.009^c

Negative

20/85 (23.5)

10.80 (2.16, 53.40)

91,822
(30,882, 242,450)

MRI

Positive

25/77 (32.5)

0.581^a

7.92 (2.16, 53.40)

0.503^c

118,884
(30,882, 260,000)

0.850^c

Negative

11/40 (27.5)

8.00 (2.88, 44.70)

132,304
(51,161, 242,450)

Disease duration
(months)

≤ 8

16/44 (36.4)

0.433^a

7.96 (2.16, 34.00)

0.797^c

113,832
(52,188, 242,450)

0.268^c

> 8

15/52 (28.8)

7.92 (2.16, 53.40)

146,947
(30,882, 260,000)

　　Note. ^aChi-Square test was used for comparing the positive rate of each factor groups. ^bKruskal-Wallis H test was used for comparing the positive time post-reaction and the peak ThT fluorescence units of each factor that more than two groups. ^cMann-Whitney U test was used for comparing the positive time post-reaction and the peak ThT fluorescence units of each factor between two groups.

Mutants

Positive rate (%)

Positive time post-reaction (h)

Peak ThT fluorescence units (rfu)

Positive no./grouped no.

P-value

Median (min, max)

P-value

Median (min, max)

P-value

P102L

6/10 (60.0)

0.032^a

9.04 (3.72, 18.00)

0.026^b

148,689 (46,332, 184,010)

0.211^b

D178N

6/37 (16.2)

27.80 (2.88, 53.40)

66,156 (30,881, 223,636)

T188K

9/35 (25.7)

8.00 (5.76, 19.44)

112,449 (52,188, 242,450)

E196A

4/10 (40.0)

11.52 (5.04, 20.16)

90,851 (56,926, 250,143)

E200K

11/25 (44.0)

3.60 (2.16, 10.80)

153,321 (87,548, 260,000)

　　Note. ^aChi-Square test was used to compare the positive rates among the five types of gPrDs. ^bKruskal-Wallis H test was used to compare the positive time post-reaction and the peak ThT fluorescence units among the five types of gPrDs.

Grouped

Mutants

Positive rate (%)

Positive time post-reaction (h)

Peak ThT fluorescence units (rfu)

Positive no./grouped no.

P-value

Median (min, max)

P-value

Median (min, max)

P-value

FFI

D178N

6/37 (16.2)

0.048^a

27.80 (2.88, 53.40)

0.091^b

66,156 (30,881, 223,636)

0.087^b

gCJD

T188K

24/70 (34.3)

7.71 (2.16, 20.16)

118,873 (52,188, 260,000)

E196A

E200K

GSS

P102L

6/10 (60.0)

0.116^a

9.04 (3.72, 18.00)

0.364^b

148,689 (46,332, 184,010)

0.876^b

gCJD

T188K

24/70 (34.3)

7.71 (2.16, 20.16)

118,873 (52,188, 260,000)

E196A

E200K

GSS

P102L

6/10 (60.0)

0.005^a

9.04 (3.72, 18.00)

0.337^b

148,689 (46,332, 184,010)

0.310^b

FFI

D178N

6/37 (16.2)

27.8 (2.88, 53.40)

66,156 (30,881, 223,636)

　　Note. ^aChi-Square test was used for comparing the positive rate between two groups of gPrDs. ^bMann-Whitney U test was used for comparing the positive time post-reaction and the peak ThT fluorescence units between two groups of gPrDs.

Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

基金项目: This work was supported by National Natural Science Foundation of China [81772197, 81401670, 81630062]; National Key Research and Development Program of China [2018YFC1200305]; National Science and Technology Major Project of China [2018ZX10102001]; SKLID Development Grant [2019SKLID401, 2019SKLID603, 2016SKLID603]; and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018RC330004]

作者简介:
HU Chao, male, born in 1992, PhD Candidate, majoring in immunology

CHEN Cao, male, born in 1983, PhD, majoring in immunology

通讯作者: DONG Xiao Ping, Tel/Fax: 86-10-58900815, E-mail: dongxp238@sina.com

收稿日期: 2020-12-20

录用日期: 2021-04-12

刊出日期: 2021-10-29

注释:

Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

1. State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China

2. Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 420115, Hubei, China

3. College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163711, Heilongjiang, China

4. China Academy of Chinese Medical Sciences, Beijing 100700, China

5. Center for Global Public Health, Chinese Center for Disease Control and Prevention, Beijing 102206, China

Author Bio:
HU Chao, male, born in 1992, PhD Candidate, majoring in immunology

CHEN Cao, male, born in 1983, PhD, majoring in immunology

Corresponding author: DONG Xiao Ping, Tel/Fax: 86-10-58900815, E-mail: dongxp238@sina.com

^&These authors contributed equally to this work.

Received Date: 2020-12-20

Accepted Date: 2021-04-12

Publish Date: 2021-10-29

^&These authors contributed equally to this work.

全文HTML

Prion diseases (PrDs) are fatal neurodegenerative conditions that affect humans and other mammals, which consist of sporadic, genetic, and acquired forms in human PrDs^[1]. The genetic form accounts for approximately 5%–15% of all human PrDs. Human genetic prion diseases (gPrDs) are further classified as genetic Creutzfeldt-Jakob disease (gCJD), Gerstmann-Sträussler syndrome (GSS), and fatal familial insomnia (FFI), according to the differences in genetic variants, clinical symptoms, and neuropathology^[2]. To date, more than 60 PRNP mutants have been reported worldwide, most of which are pathological^[3]. The clinical and histopathological characteristics of gPrDs vary greatly depending on the different PRNP mutations. The proportion of PrDs caused by PRNP mutations differs notably among countries and/or geographic regions, which is closely linked to racial diversity.

Since 2006, the China National Surveillance for Creutzfeldt-Jacob disease has identified 20 gPrDs-associated mutations in PRNP (Shi et al., in preparation). The top five types of mutations in the Chinese population were T188K, D178N, E200K, E196A, and P102L. T188K gCJD is the most commonly identified gPrDs in Chinese but very rare in other countries, including the neighboring countries (Japan and South Korea)^[4]. D178N FFI, one of the most frequent gPrDs worldwide, is commonly observed in Chinese, whose frequency seems to be higher than that in Japanese and Korean. The E200K gCJD is the most popular gCJD in Europe, while it is also relatively common among the Chinese. E196A gCJD is extremely rare globally, but more than 10 cases have been reported in China. The clinical manifestations of T188K, E200K, and E196A gCJD are comparable to those of sCJD, which is usually difficult to differentiate without gene sequencing^[5]. Similar to many countries, P102L GSS is also the predominant subtype of GSS among the Chinese.

Real-time quaking-induced conversion (RT-QuIC) is a technique that can detect small amounts of PrP^Sc in various tissues, including cerebrospinal fluid (CSF)^[6]. The implementation and significance of CSF RT-QuIC in patients with sCJD have been described^[7,8]; however, its application to gPrDs, particularly in Chinese gPrDs, is not well documented. Meanwhile, the difference in the reactivity of CSF RT-QuIC in various gPrDs remains unsolved. To address these questions, a total of 117 CSF samples from Chinese gPrDs cases with five major types of mutations were enrolled in this study and their RT-QuIC reactivities, focusing on the positive rate, conversion time, and peak of relative ThT fluorescence units (rfu) were compared with other main clinical, epidemiological, and laboratory factors.

The stored intravitally collected CSF samples from 117 patients with gPrDs confirmed by PRNP sequencing were subjected to the established RT-QuIC assay. We included 10 cases of P102L GSS, 37 cases of D178N FFI, 35 cases of T188K gCJD, 10 cases of E196A gCJD, and 25 cases of E200K gCJD. In total, 36 out of 117 (30.8%) CSF samples were positive in RT-QuIC, showing remarkable various kinetic patterns in the lag phase time and the maximum rfu reached. The potential general relationship of CSF RT-QuIC reactivity in gPrDs cases was analyzed with some major factors. Only periodic sharp wave complexes (PSWC) in electroencephalogram (EEG) showed a significant association with RT-QuIC reactivity (positive rate, P = 0.006; conversion time, P = 0.005; peak of rfu, P = 0.009), whereas the other factors were not significant (Supplementary Table S1, available in www.besjournal.com).

Table S1. Correlation of reactivity of CSF RT-QuIC with factors of genetic prion diseases

Factors	Grouped	Positive rate (%)		Positive time post-reaction (h)		Peak ThT fluorescence units (rfu)
Factors	Grouped	Positive no./ grouped no.	P-value	Median (min, max)	P-value	Median (min, max)	P-value
Age (years)	< 50	13/35 (37.1)	0.376^a	8.64 (2.88, 53.40)	0.369^b	141,434 (30,882, 260,000)	0.455^b
	50–70	22/74 (29.7)		7.56 (2.16, 21.60)		127,168 (52,188, 250,144)
	> 70	1/8 (12.5)		20.16		62,818
Gender	Male	18/58 (31.0)	0.951^a	7.96 (2.88, 44.70)	0.254^c	116,813 (51,161, 245,791)	0.569^c
Gender	Female	18/59 (30.5)	0.951^a	5.76 (2.16, 53.40)	0.254^c	143,248 (30,882, 260,000)	0.569^c
Tau ELISA (pg/mL)	< 1,400	16/58 (27.6)	0.460^a	6.12 (2.16, 44.70)	0.425^c	118,388 (51,161, 250,144)	0.340^c
Tau ELISA (pg/mL)	≥ 1,400	20/59 (33.9)	0.460^a	8.00 (2.16, 53.40)	0.425^c	132,739 (30,882, 260,000)	0.340^c
14-3-3Western blot	Positive	22/71 (31.0)	0.950^a	5.76 (2.16, 44.70)	0.172^c	126,029 (51,161, 260,000)	0.559^c
14-3-3Western blot	Negative	14/46 (30.4)	0.950^a	9.04 (2.16, 53.40)	0.172^c	127,168 (30,882, 223,636)	0.559^c
EEG	Positive	16/32 (50.0)	0.006^a	4.32 (2.16, 12.24)	0.005^c	151,876 (87,548, 260,000)	0.009^c
EEG	Negative	20/85 (23.5)	0.006^a	10.80 (2.16, 53.40)	0.005^c	91,822 (30,882, 242,450)	0.009^c
MRI	Positive	25/77 (32.5)	0.581^a	7.92 (2.16, 53.40)	0.503^c	118,884 (30,882, 260,000)	0.850^c
MRI	Negative	11/40 (27.5)	0.581^a	8.00 (2.88, 44.70)	0.503^c	132,304 (51,161, 242,450)	0.850^c
Disease duration (months)	≤ 8	16/44 (36.4)	0.433^a	7.96 (2.16, 34.00)	0.797^c	113,832 (52,188, 242,450)	0.268^c
Disease duration (months)	> 8	15/52 (28.8)	0.433^a	7.92 (2.16, 53.40)	0.797^c	146,947 (30,882, 260,000)	0.268^c
*Note.* ^aChi-Square test was used for comparing the positive rate of each factor groups. ^bKruskal-Wallis H test was used for comparing the positive time post-reaction and the peak ThT fluorescence units of each factor that more than two groups. ^cMann-Whitney U test was used for comparing the positive time post-reaction and the peak ThT fluorescence units of each factor between two groups.

Under our experimental conditions, the positive rates were 60.0% in P102L GSS, 16.2% in D178N FFI, 25.7% in T188K gCJD, 40.0% in E196A gCJD, and 44.0% in E200K gCJD (Table 1), with a statistically significant difference (P = 0.032). The real-time rfu data of every positive sample were collected, and the individual averaged RT-QuIC reactive curves of gPrDs were generated. As shown in Figure 1 (various controls in each reaction are illustrated in Supplementary Figure S1, available in www.besjournal.com), E200K-gCJD showed the shortest conversion time and the highest average peak of rfu (> 150,000 rfu), whose averaged curve reached the maximal rfu approximately 10 h post-reaction. T188K-gCJD and E196A-gCJD revealed similar reactive patterns, with relatively long lag times and moderate levels of the averaged peak of rfu (around 100,000 rfu). The lag time of P102L-GSS was similar to that of E196A-gCJD, but the maximal rfu was slightly higher. D178N-FFI showed the longest lag time and the lowest average peak of rfu, which was approximately 65000. Statistical analysis revealed a significant difference in the positive conversion time of RT-QuIC (P = 0.026) among the five types of gPrDs, but not in the rfu at peak (P = 0.211) (Table 1). This indicates a close association between the genotypes of gPrDs and their CSF RT-QuIC reactivity.

Table 1. Correlation of reactivity of CSF RT-QuIC with PrP mutants

Mutants	Positive rate (%)		Positive time post-reaction (h)		Peak ThT fluorescence units (rfu)
Mutants	Positive no./grouped no.	P-value	Median (min, max)	P-value	Median (min, max)	P-value
P102L	6/10 (60.0)	0.032^a	9.04 (3.72, 18.00)	0.026^b	148,689 (46,332, 184,010)	0.211^b
D178N	6/37 (16.2)		27.80 (2.88, 53.40)		66,156 (30,881, 223,636)
T188K	9/35 (25.7)		8.00 (5.76, 19.44)		112,449 (52,188, 242,450)
E196A	4/10 (40.0)		11.52 (5.04, 20.16)		90,851 (56,926, 250,143)
E200K	11/25 (44.0)		3.60 (2.16, 10.80)		153,321 (87,548, 260,000)
*Note.* ^aChi-Square test was used to compare the positive rates among the five types of gPrDs. ^bKruskal-Wallis H test was used to compare the positive time post-reaction and the peak ThT fluorescence units among the five types of gPrDs.

Figure 1. Averaged reactive curves of CSF RT-QuIC of the five gPrDs. The data are obtained from the positive samples, including nine cases of T188K-gCJD, four cases of E196A-gCJD, eleven cases of E200K-gCJD, six cases of D178N-FFI, and seven cases of P102L-GSS. The averaged data of each type of gPrDs were calculated and presented as mean + SD. X-axis, reaction time; Y-axis, ThT fluorescence units.

Figure S1. Various control curves of CSF RT-QuIC. The averaged data of each control were calculated and presented as mean + SD. X-axis, reaction time; Y-axis, ThT fluorescence units.

The reactivities of CSF RT-QuIC were also different among the clinical phenotypes of gCJD, FFI, and GSS. Taken together, 70 gCJD cases with the mutants T188K, E196A, and E200K, 24 (34.3%), were positive for RT-QuIC. The median positive conversion time was 7.71 h (2.16−20.16), and the median peak of rfu was 118,873 (52,188−260,000). Statistical assays revealed significant differences between the positive rates of FFI and gCJD (P = 0.048) and between FFI and GSS (P = 0.005), but not between gCJD and GSS (P = 0.116). No statistical difference in the conversion time and peak of rfu was observed among the three phenotypes (Table 1).

The possible association of the reactivity of CSF RT-QuIC for each genotype with the main CJD-related parameters was also evaluated individually (Supplementary Table S2, available in www.besjournal.com). Only in the group of E200K-gCJD, statistical significance in the relation of MRI abnormality with positive rate and in that of disease duration with the peak of rfu were observed. Other tested parameters did not reveal any statistical association with RT-QuIC reactivity in any of the five types of gPrDs. This implies that the reactivity of CSF RT-QuIC of gPrDs is almost unrelated to the main CJD-associated clinical and laboratory parameters.

Table S2. Difference between gCJD (T188K, E196A, E200K), FFI (D178N) and GSS (P102L) in RT-QuIC

Grouped	Mutants	Positive rate (%)		Positive time post-reaction (h)		Peak ThT fluorescence units (rfu)
Grouped	Mutants	Positive no./grouped no.	P-value	Median (min, max)	P-value	Median (min, max)	P-value
FFI	D178N	6/37 (16.2)	0.048^a	27.80 (2.88, 53.40)	0.091^b	66,156 (30,881, 223,636)	0.087^b
gCJD	T188K	24/70 (34.3)		7.71 (2.16, 20.16)		118,873 (52,188, 260,000)
	E196A
	E200K
GSS	P102L	6/10 (60.0)	0.116^a	9.04 (3.72, 18.00)	0.364^b	148,689 (46,332, 184,010)	0.876^b
gCJD	T188K	24/70 (34.3)		7.71 (2.16, 20.16)		118,873 (52,188, 260,000)
	E196A
	E200K
GSS	P102L	6/10 (60.0)	0.005^a	9.04 (3.72, 18.00)	0.337^b	148,689 (46,332, 184,010)	0.310^b
FFI	D178N	6/37 (16.2)	0.005^a	27.8 (2.88, 53.40)	0.337^b	66,156 (30,881, 223,636)	0.310^b
*Note.* ^aChi-Square test was used for comparing the positive rate between two groups of gPrDs. ^bMann-Whitney U test was used for comparing the positive time post-reaction and the peak ThT fluorescence units between two groups of gPrDs.

Our data here display significantly different reactive patterns of CSF RT-QuIC in the five types of Chinese gPrDs cases. It is well known that there are clear differences in the clinical, neuropathological, and laboratory characteristics of gCJD, GSS, and FFI^[9]. Even in gCJD displaying similar features as sCJD, there are still slight differences among various genotypes. For example, our surveillance data of T188K, E196A, and E200K gCJD patients showed lower ratios of mutism, CSF 14-3-3 positivity, and increased CSF tau levels (Shi et al., in preparation). Diversity in the reactivity of CSF RT-QuIC among various gPrDs is also likely a reflection of the different neuropathogenesis.

RT-QuIC reactivity is closely related to the amount of PrP^Sc in the testing specimens^[10]. The presence of PrP^Sc in the CNS is a hallmark of prion disease. GSS is characterized by the presence of large PrP^Sc plaques in the brain, particularly in the cerebellum tissue^[9]. Amounts of PrP^Sc are also observable in the brain tissues of most gCJD cases, which are usually indistinguishable from sCJD. On the contrary, the brain tissues of FFI patients usually contain much less PrP^Sc, even undetectable by routine methods, such as proteinase K-digested western blot. Such differences in brain PrP^Sc are also reflected in the reactivity of CSF RT-QuIC. We also noticed higher positive rates of CSF RT-QuIC in the E200K and E196A gCJD groups than in the T188K gCJD group. The characteristics of brain PrP^Sc in E200K gCJD are well addressed as one of the most common genotypes of gPrDs worldwide. Most T188K gCJD and all E196A gCJD have been identified in China. Unfortunately, only a few T188K Caucasian cases and none of the E196A cases have documented neuropathological feature^[4]. The exact association between brain PrP^Sc and CSF RT-QuIC reactivity among the three genotypes of gCJD is still unclear.

We noticed that the RT-QuIC reactivity showed an obvious individual appearance. According to our analysis, the majority of the indexes seem to be unrelated to the RT-QuIC reactivity, except for PSWC on EEG. However, such an association was observed in the analysis of the five gPrDs, but not in those of individual genotypes. More cases of D178N FFI, which were all negative in PSWC on EEG and low positive rate in RT-QuIC, created such a phenomenon. Individual differences in the same gPrDs genotype are also frequently observed in other CSF tests, such as CSF 14-3-3 and tau. Besides the amount of brain PrP^Sc, there are probably other unknown elements influencing the release of brain factors into the CSF.

We have to admit that the positive rates of RT-QuIC in this study, regardless of the type of gPrDs, are relatively low, probably due to some reasons. However, the major objective of this study was to determine the possible differences in the various gPrDs in RT-QuIC rather than to prove the feasibility of RT-QuIC in the diagnosis of gPrDs. Therefore, the relatively less sensitive experimental condition here is somehow more suitable for identifying the slight differences that might be hidden in the higher sensitivity assay among various genotypes of gPrDs.

CH and CC designed the study, drafted the manuscript, and performed the RT-QuIC assay. QS and KX performed data analysis. JC, WZ, YX, WY, and LW carried out data sorting and statistical analysis. XPD conceived the study, participated in its design, and drafted the manuscript. All authors read and approved the final manuscript.

All authors declare that they have no conflict of interest.

参考文献 (10)

补充材料:

20519Supplementary Materials.pdf

[1]	Prusiner SB, Scott MR, DeArmond SJ, et al. Prion protein biology. Cell, 1998; 93, 337−48. doi: 10.1016/S0092-8674(00)81163-0
[2]	Chen C, Dong XP. Epidemiological characteristics of human prion diseases. Infect Dis Poverty, 2016; 5, 47. doi: 10.1186/s40249-016-0143-8
[3]	Mead S, Lloyd S, Collinge J. Genetic factors in mammalian prion diseases. Annu Rev Genet, 2019; 53, 117−47. doi: 10.1146/annurev-genet-120213-092352
[4]	Shi Q, Zhou W, Chen C, et al. Rare genetic Creutzfeldt-Jakob disease with T188K mutation: analysis of clinical, genetic and laboratory features of 30 Chinese patients. J Neurol Neurosurg Psychiatry, 2017; 88, 889−90. doi: 10.1136/jnnp-2016-314868
[5]	Chen C, Hu C, Shi Q, et al. Profiles of 14-3-3 and total tau in CSF samples of Chinese patients of different genetic prion diseases. Front Neurosci, 2019; 13, 934. doi: 10.3389/fnins.2019.00934
[6]	Schmitz M, Cramm M, Llorens F, et al. The real-time quaking-induced conversion assay for detection of human prion disease and study of other protein misfolding diseases. Nat Protoc, 2016; 11, 2233−42. doi: 10.1038/nprot.2016.120
[7]	Xiao K, Yang XH, Zou WQ, et al. Assessment of the sensitivity and specificity of the established Real-time Quaking-induced Conversion (RT-QuIC) technique in Chinese CJD surveillance. Biomed Environ Sci, 2020; 33, 620−2.
[8]	Groveman BR, Orrú CD, Hughson AG, et al. Extended and direct evaluation of RT-QuIC assays for Creutzfeldt-Jakob disease diagnosis. Ann Clin Transl Neurol, 2017; 4, 139−44. doi: 10.1002/acn3.378
[9]	Schmitz M, Dittmar K, Llorens F, et al. Hereditary human prion diseases: an update. Mol Neurobiol, 2017; 54, 4138−49. doi: 10.1007/s12035-016-9918-y
[10]	Green AJE. RT-QuIC: a new test for sporadic CJD. Pract Neurol, 2019; 19, 49−55. doi: 10.1136/practneurol-2018-001935

[1]	HE La Gu, LIANG Yun Lai, YANG Lu Qi, YUAN Hua Min. Prognostic Nutritional Index Associates with the Severity of Silicosis: A Study from a Tertiary Class A Prevention and Treatment Institute for Occupational Diseases in China . Biomedical and Environmental Sciences, 2024, 37(1): 122-126. doi: 10.3967/bes2024.012
[2]	ZHANG Ying, QU Jiang Wen, ZHENG Min Na, DING Ya Xing, CHEN Wei, YE Shao Dong, LI Xiao Yan, LI Yan Kun, LIU Ying, ZHU Di, JIN Can Rui, WANG LIN, YANG Jin Ye, ZHAI Yu, WANG Er Qiang, MENG Xing. Neutralizing Antibody Responses against Five SARS-CoV-2 Variants and T Lymphocyte Change after Vaccine Breakthrough Infections from the SARS-CoV-2 Omicron BA.1 Variant in Tianjin, China: A Prospective Study . Biomedical and Environmental Sciences, 2023, 36(7): 614-624. doi: 10.3967/bes2023.047
[3]	QU Feng Tian, WANG Wen Qing, LIU Qian, ZHOU Hai Jian, HU Jin Rui, DU Xiao Li, WANG Yue, XUE Jia Qi, CUI Zhi Gang, XIE Gui Lin, MENG Shuang. Genetic Diversity, Antibiotic Resistance, and Pathogenicity of Aeromonas Species from Food Products in Shanghai, China . Biomedical and Environmental Sciences, 2022, 35(9): 842-853. doi: 10.3967/bes2022.108
[4]	WANG Jia Qi, CHEN Xiao Li, ZHOU Gui Lan, WANG Hai Rui, GU Yi Xin, ZHANG Jian Zhong, SHAO Zhu Jun, ZHANG Mao Jun. Genetic Characteristics of Lipooligosaccharide and Capsular Polysaccharide of Campylobacter jejuni from Different Sources in China . Biomedical and Environmental Sciences, 2022, 35(12): 1106-1114. doi: 10.3967/bes2022.140
[5]	MENG Shuang, DU Xiao Li, WANG Yong Lu, QU Feng Tian, XIE Gui Lin, ZHOU Hai Jian, HU Jin Rui, QIN Zheng, WANG Yue, KAN Biao, CUI Zhi Gang. Comparative Study of the Genetic Diversity, Antimicrobial Resistance, and Pathogenicity of Aeromonas Isolates from Clinical Patients and Healthy Individuals . Biomedical and Environmental Sciences, 2021, 34(6): 454-464. doi: 10.3967/bes2021.062
[6]	WANG Yuan Yuan, ZHOU Gui Lan, LI Ying, GU Yi Xin, HE Mu, ZHANG Shuang, JI Guo Qiang, YANG Jie, WANG Miao, MA Hong Mei, ZHANG Mao Jun. Genetic Characteristics and Antimicrobial Susceptibility of Arcobacter butzleri Isolates from Raw Chicken Meat and Patients with Diarrhea in China . Biomedical and Environmental Sciences, 2021, 34(12): 1024-1028. doi: 10.3967/bes2021.139
[7]	LI Man, WANG Zhuo Qun, ZHANG Lu, ZHENG Hao, LIU Dian Wu, ZHOU Mai Geng. Burden of Cirrhosis and Other Chronic Liver Diseases Caused by Specific Etiologies in China, 1990−2016: Findings from the Global Burden of Disease Study 2016 . Biomedical and Environmental Sciences, 2020, 33(1): 1-10. doi: 10.3967/bes2020.001
[8]	MENG Shuang, WANG Yong Lu, LIU Chen Geng, YANG Jing, YUAN Min, BAI Xiang Ning, JIN Dong, LIANG Jun Rong, CUI Zhi Gang, LI Juan. Genetic Diversity, Antimicrobial Resistance, and Virulence Genes of Aeromonas Isolates from Clinical Patients, Tap Water Systems, and Food . Biomedical and Environmental Sciences, 2020, 33(6): 385-395. doi: 10.3967/bes2020.053
[9]	CHEN Wei, WENG Yu Wei, HE Wen Xiang, ZHU Ying, YU Ting Ting, XIE Jian Feng, ZHENG Kui Cheng, YAN Yan Sheng, ZHANG Yong Jun, ZHANG Wen Chang. RT-nPCR Assays for Amplification and Sequencing of VP1 Genes in Human Enterovirus A–D from Clinical Specimens . Biomedical and Environmental Sciences, 2020, 33(11): 829-838. doi: 10.3967/bes2020.113
[10]	XIAO Kang, YANG Xue Hua, ZOU Wen Quan, DONG Xiao Ping, SHI Qi. Assessment of the Sensitivity and Specificity of the Established Real-time Quaking-induced Conversion (RT-QuIC) Technique in Chinese CJD Surveillance . Biomedical and Environmental Sciences, 2020, 33(8): 620-622. doi: 10.3967/bes2020.081
[11]	JU Chang Yan, ZHANG Mao Jun, MA Yan Ping, LU Jing Rang, YU Mu Hua, CHEN Hui, LIU Chu Yun, GU Yi Xin, FU Yan Yan, DUAN Yong Xiang. Genetic and Antibiotic Resistance Characteristics of Campylobacter jejuni Isolated from Diarrheal Patients, Poultry and Cattle in Shenzhen . Biomedical and Environmental Sciences, 2018, 31(8): 579-585. doi: 10.3967/bes2018.079
[12]	LI Xue Lian, XIE Na, WANG Song Wang, WU Qian Hong, MA Yan, SHU Wei, CHEN Hong Mei, ZHANG Li Qun, WU Xiao Guang, MA Li Ping, CHE Nan Ying, GAO Meng Qiu. Diagnostic Value of Cerebrospinal Fluid T-SPOT.TB for Tuberculousis Meningitis in China . Biomedical and Environmental Sciences, 2017, 30(9): 681-684. doi: 10.3967/bes2017.091
[13]	KE Shen, KE Qin Mei, JIA Wen Jing, CHENG Xi Yu, LI Hao, ZHANG Jie Ying, LUO Hui Fang, HE Jin Sheng, CHEN Zhi Nan. Benchmark Dose Estimation for Cadmium-Induced Renal Effects Based on a Large Sample Population from Five Chinese Provinces . Biomedical and Environmental Sciences, 2015, 28(5): 383-387. doi: 10.3967/bes2015.054
[14]	DONG Yin Ping, CHEN Qian, CUI Sheng Hui, LI Feng Qin. Enumeration, Genetic Characterization and Antimicrobial Susceptibility of Lactobacillus and Streptococcus Isolates from Retail Yoghurt in Beijing, China . Biomedical and Environmental Sciences, 2014, 27(9): 740-748. doi: 10.3967/bes2014.109
[15]	CHANG Man Li, SHAO Bing, LIU Yan Hong, LI Lu Lu, PEI Li Chun, WANG Bin You. Analysis of Allergens in 5473 Patients with Allergic Diseases in Harbin, China . Biomedical and Environmental Sciences, 2013, 26(11): 886-893. doi: 10.3967/bes2013.017
[16]	JIANG Feng, LI Qing, HU Cheng, ZHANG Rong, WANG Cong Rong, YU Wei Hui, LU Jing Yi, TANG Shan Shan, BAO Yu Qian, XIANG Kun San, JIA Wei Ping. Association of a SLC30A8 Genetic Variant with Monotherapy of Repaglinide and Rosiglitazone Effect in Newly Diagnosed Type 2 Diabetes Patients in China . Biomedical and Environmental Sciences, 2012, 25(1): 23-29. doi: 10.3967/0895-3988.2012.01.004
[17]	WANG YanHua, HAI Rong, ZHANG ZhiKai, XIA LianXu, CAI Hong, LIANG Ying, SHEN XiaoNa, YU DongZheng. Genetic Relationship between Francisella Tularensis Strains from China and from Other Countries . Biomedical and Environmental Sciences, 2011, 24(3): 310-314. doi: 10.3967/0895-3988.2011.03.015
[18]	HAI-JUN WANG, HENG ZHANG, SHI-WEI ZHANG, YONG-PING PAN, JUN MA. Association of the Common Genetic Variant Upstream of INSIG2 Gene with Obesity Related Phenotypes in Chinese Children and Adolescents . Biomedical and Environmental Sciences, 2008, 21(6): 528-536.
[19]	JIAN-LIN LOU, ZHI-JIAN CHEN, JIANG WEI, JI-LIANG HE, LI-FEN JIN, SHI-JIE CHEN, WEI ZHENG, SHI-JIE XU. Response of Lymphocytes to Radiation in Untreated Breast Cancer Patients as Detected with Three Different Genetic Assays . Biomedical and Environmental Sciences, 2008, 21(6): 499-508.
[20]	YING-WEI CHEN, WEN-XIN LUO, MING-QIAO WANG, JIN WANG, LI-FENG LI, QUAN YUAN, JUN ZHANG, NING-SHAO XIA. Isolation of Human Antibodies Against Hepatitis E From Phage Display Library by Metal Affinity Chromatography . Biomedical and Environmental Sciences, 2007, 20(6): 488-494.

doi: 10.3967/bes2021.113

Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

Author Bio:
HU Chao, male, born in 1992, PhD Candidate, majoring in immunology

CHEN Cao, male, born in 1983, PhD, majoring in immunology

Corresponding author: DONG Xiao Ping, Tel/Fax: 86-10-58900815, E-mail: dongxp238@sina.com

计量

Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

doi: 10.3967/bes2021.113

作者简介:
HU Chao, male, born in 1992, PhD Candidate, majoring in immunology

CHEN Cao, male, born in 1983, PhD, majoring in immunology

通讯作者: DONG Xiao Ping, Tel/Fax: 86-10-58900815, E-mail: dongxp238@sina.com

English Abstract

Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

Author Bio:
HU Chao, male, born in 1992, PhD Candidate, majoring in immunology

CHEN Cao, male, born in 1983, PhD, majoring in immunology

Corresponding author: DONG Xiao Ping, Tel/Fax: 86-10-58900815, E-mail: dongxp238@sina.com

全文HTML

目录

doi: 10.3967/bes2021.113

Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

Author Bio: HU Chao, male, born in 1992, PhD Candidate, majoring in immunology CHEN Cao, male, born in 1983, PhD, majoring in immunology

Corresponding author: DONG Xiao Ping, Tel/Fax: 86-10-58900815, E-mail: dongxp238@sina.com

计量

出版历程

Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

doi: 10.3967/bes2021.113

作者简介: HU Chao, male, born in 1992, PhD Candidate, majoring in immunology CHEN Cao, male, born in 1983, PhD, majoring in immunology

通讯作者: DONG Xiao Ping, Tel/Fax: 86-10-58900815, E-mail: dongxp238@sina.com

English Abstract

Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

Author Bio: HU Chao, male, born in 1992, PhD Candidate, majoring in immunology CHEN Cao, male, born in 1983, PhD, majoring in immunology

Corresponding author: DONG Xiao Ping, Tel/Fax: 86-10-58900815, E-mail: dongxp238@sina.com

全文HTML

目录

Author Bio:
HU Chao, male, born in 1992, PhD Candidate, majoring in immunology

CHEN Cao, male, born in 1983, PhD, majoring in immunology

作者简介:
HU Chao, male, born in 1992, PhD Candidate, majoring in immunology

CHEN Cao, male, born in 1983, PhD, majoring in immunology

Author Bio:
HU Chao, male, born in 1992, PhD Candidate, majoring in immunology

CHEN Cao, male, born in 1983, PhD, majoring in immunology