Identification of Misfolded Proteins in Body Fluids for the Diagnosis of Prion Diseases

Table 1

Detection of misfolded PrP in body fluids.

Assay^1	Species	Body fluid	Assay sensitivity (brain dilution)^2	Inoculation route	Time (dpi)	Starting volume (mL)	Number of tested samples (treated/controls)	Sensitivity (%)	Specificity (%)	Reference
					14	1	5/5	0	100
					20	1	6/4	50	100
					40	1	10/5	60	100
			10^−12 (fg)	ip	60	1	5/4	40	100	[28]
		Blood (bc)			70	1	5/5	20	100
					80	1	5/5	0	100
	Hamster				90 (c.s.)	1	10/10	80	100
			10^−12 (fg)	ic	68 (c.s.)	1	18/12	89	100	[27]
			10^−12 (fg)	ic	60	1.5	4/3	100	100	[29]
					68 (c.s.)	1.5	3/3	100	100
		Blood (plasma)	10^−12 (fg)	ic	60	1.5	4/5	50	100	[29]
					68 (c.s.)	1.5	4/5	67	100
		Urine	10^−12 (fg)	ic	68 (c.s.)	0.02	7/4	86	100	[29]
				oi	155 (c.s.)	0.02	7/4	67	100
			(—)	ip	90 (c.s.)	(—)	5/5	80	100	[30]
PMCA		CSF	(ag)	ic	68 (c.s.)	0.002	6/14	100	100	[32]
					30	10^4	1/2	0	100
					60	10^+4 (cells)	1/2	0	100
		Blood (wbc)	10^−8	oi	90	10^+4 (cells)	1/2	100	100	[33]
					130	10^+4 (cells)	1/2	100	100
					190 (c.s.)	10^+4 (cells)	1/2	100	100
	Sheep		10^−9	ni	c.s.	10^+7 (cells)	10/8	100	100^3	[20]
		Blood (plasma)	10^−8	ni/oi^4	b.c.s.	0.5	6/7	100	100	[34]
					c.s.	0.5	9/7	100	100
		Urine	10^−8	ni/oi^4	c.s.	0.5	4/4	100	100	[35]
		Saliva	(fg)	ni	360	(—)	12/20	100	88	[36]
	Cattle	Saliva	10^−11 (fg)	oi	c.s.	0.005	3/1	33	100	[37]
		CSF	10^−11 (fg)	oi	c.s.	0.005	3/1	33	100
		Blood (plasma)	10^−8	oi	b.c.s.	0.5	2/1	100	100	[34]
	Cervids				c.s.	0.5	3/1	100	100
		Urine	10^−8	oi	c.s.	0.5	5/2	100	100	[35]
		CSF	10^−5	ni	c.s.	0.025	4/31	75	100	[38]
					10	0.5	1/11	100	100
		Blood (plasma)	4 × 10^−14 (ag)^5	ic	30	0.5	3/11	100	100	[39]
	Hamster				80 (c.s.)	0.5	9/11	100	100
		CSF	10^−9	ic	c.s.	0.002	2/2	100	100	[40]
		Nasal lavage	10^−9	ic	c.s.	0.004	8/2	100	100	[40]
	Sheep	CSF	(fg)	ni	c.s.	0.005	1/1	100	100	[41]
QUIC		Spiked vCJD blood (plasma)	4 × 10^−14 (ag)^5	ni	c.s.	0.5	4/4	100	100	[39]
		sCJD CSF	10^−9 (fg)^6	ni	c.s.	0.005	16/14	87.5	100	[42]
			5 × 10^−6 (0.1 pg)	ni	c.s.	0.015	67/51	87	100	[43]
	Human	gCJD CSF (E200K)	10^−9 (fg)^6				22/1	87	100
		gCJD CSF (V203I)	10^−9 (fg)^6	ni	c.s.	0.005	2/1	100	100	[44]
		GSS CSF	10^−9 (fg)^6				20/1	78	100
		FFI CSF	10^−9 (fg)^6				12/1	100	100
ICE	Human	CJD Blood (bc)	(—)	ni	c.s.	10	9/6	55	100	[45]
sFIDA	Sheep	Blood (plasma)	(—)	ni	c.s.	(—)	10/5	100	100	[46]
	Cattle	CSF	(—)	oi	c.s.	0.02	6/6	50	100	[47]
Ligand-based IA		Blood (wbc)	(—)	ni	b.c.s.	5	23/129	56	100
	Sheep	Blood (wbc)	(—)	ni	c.s.	5	80/129	55	100	[48]
		Blood (wbc)	(—)	oi	c.s.	5	7/129	71	100
Metal matrix	Human	vCJD blood	10^−10(5)	ni	c.s.	(—)	21/190	70	100	[49]
		sCJD blood					27/190	0	100
EP-vCJD	Human	Spiked vCJD blood	5 × 10^−7(5)	ni	c.s.	(—)	nd/1000	100	100	[50]
		vCJD blood		ni	c.s.	(—)	3/20000	0	98	[51–53]
CDI	Human	vCJD blood	10^−5(5)	ni	c.s.	(—)	7/4	100	100	[54]
		sCJD blood (wbc)	0.5 pg	ni	c.s.	10^+6 cells	24/27	0	100	[55]
MPD	Sheep	Blood (serum)		ni	c.s.	0.2	13/1	100	100	[54]
	Primates	Blood (plasma)	1 ID/mL^7	ni	c.s.	0.2	8/4	100	100	[56]
	Human	sCJD Blood (plasma)		ni	c.s.	0.2	5/5	100	100
MDS	Hamster	Blood (plasma)	10^−8	(—)	c.s.	0.078	9/9	100	100	[57]

1The assay specification does not include protocol variations.
²Assay sensitivity is indicated as the end point dilution of scrapie brain homogenates. In brackets, estimates of the PrP^TSE amount provided by the authors.
³Spontaneous formation of misfolded PrP was reported in some control samples after increased cycles of sonication.
⁴Authors used samples from both naturally and experimentally infected sheep.
⁵Dilution of variant CJD brain into healthy human blood.
⁶Dilution of sporadic CJD into artificial CSF.
⁷Measured on previously titered terminal plasma pool from mice experimentally infected with the Fukuoka-1 strain of GSS.
dpi: days postinoculation; fg: femtograms; ag: attograms; bc: buffy coat; wbc: white blood cells; c.s.: clinical symptoms; b.c.s.: before clinical symptoms; ic: intracerebral; ip: intraperitoneal; oi: oral inoculation; ni: natural infection; CSF: cerebral spinal fluid; CJD: Creutzfeldt-Jakob disease; GSS: Gerstmann-Sträussler-Scheinker syndrome; FFI: fatal familial insomnia.