Table 4 Parallelism data for mHTT in the CSF of patients with HD.

From: Quantifying mutant huntingtin protein in human cerebrospinal fluid to support the development of huntingtin-lowering therapies

 

Roche

ICON

Sample

Dilution factor

Back-calculated conc. (pg/mL)

Undiluted conc. (pg/mL)

Recovery (%)

Back-calculated conc. (pg/mL)

Undiluted conc. (pg/mL)

Bias (%)

Cross-lab difference (%)

1

1

4.26

4.68

100

5.50

5.50

0

–16.1

2

2.40

5.29

113

2.63

5.26

− 4.3

0.6

3

1.57*

5.19

110.9

1.64

4.91

− 10.7

5.5

4

1.56

6.87

NA

1.69*

6.78

23.2

 

6

0.601

3.96

84.6

NV

NA

NA

 

8

0.403

3.55

75.9

0.167

1.33

− 75.7

 

Mean (pg/mL)

 

5.05

  

5.61

 

10.5

CV (%)

 

6.5

  

14.5

  

n (results within curve)

 

3

  

4

  

2

1

5.07

5.57

100

6.96

6.96

0

–22.2

2

2.53

5.57

100

3.45*

6.89

− 1.0

–21.2

3

1.79

5.90

105.9

1.60

4.79

− 31.1

 

4

1.11

4.86

87.3

1.72

6.89

− 0.9

 

6

0.762

5.03

90.3

1.02

6.11

− 12.1

 

8

0.521*

4.58

82.2

0.625

5.00

− 28.1

 

Mean (pg/mL)

 

5.68

  

6.38

 

11.6

CV (%)

 

3.4

  

16.6

  

n (results within curve)

 

3

  

4

  

3

1

5.20

5.72

100

4.86

4.86

0

16.3

2

2.45

5.40

94.4

1.97

3.95

− 18.9

31.0

3

1.55*, a

5.12

89.5

1.53

4.59

− 5.7

10.9

4

0.856

3.77

65.9

1.10

4.39

− 9.7

 

6

0.749

4.94

86.4

0.646*

3.88

− 20.3

 

8

0.454

3.99

69.8

0.803

6.43

32.1

 

Mean (pg/mL)

 

5.41

  

4.47

 

–19.0

CV (%)

 

5.5

  

10.5

  

n (results within curve)

 

3

  

3

  

4

1

5.73

6.30

100

3.50

3.50

0

57.1

2

2.83

6.23

98.9

1.60

3.20

− 8.3

64.3

3

2.20

7.27

115.4

1.01

3.04

− 13.1

 

4

1.84

8.11

128.7

0.800*

3.20

− 8.5

 

6

0.905

5.97

94.8

1.168

7.01

100.5

 

8

0.633*

5.57

88.4

0.410

3.28

− 6.2

 

Mean (pg/mL)

 

6.98

  

3.35

 

–70.3

CV (%)

 

12.8

  

6.1

  

n (results within curve)

 

4

  

2

  

5

1

8.58

9.44

100

NV

NA

NA

N/A

2

4.21

9.26

98.1

2.69

5.38

0#

53.0

3

2.57

8.48

89.8

1.77

5.32

− 1.2#

45.8

4

2.14

9.42

99.8

1.47

5.89

9.4#

46.1

6

1.20

7.91

83.8

0.699*

4.20

− 22.1#

 

8

1.05*

9.26

98.1

NV

NA

NA

 

Mean (pg/mL)

 

9.15

  

5.53

 

–49.3

CV (%)

 

5.0

  

5.6

  

n (results within curve)

 

4

  

3

  

6

1

5.95

6.54

100

4.25

4.25

0

42.4

2

2.73

6.01

91.9

1.91

3.81

− 10.2

44.8

3

NV

NA

NA

1.46*

4.39

3.3

N/A

4

1.41a

6.20

94.8

1.39

5.57

31.3

 

6

0.915

6.04

92.4

0.681

4.08

− 3.8

 

8

0.574*

5.05

77.2

0.408

3.26

− 23.1

 

Mean (pg/mL)

 

6.25

  

4.50

 

–32.6

CV (%)

 

4.3

  

16.7

  

n (results within curve)

 

3

  

4

  
  1. Serial dilution of samples from patients with mid–long polyQ-repeat lengths in surrogate matrix.
  2. *Lowest concentration for each sample providing a parallel response (i.e. recovery within 70–130%).
  3. #Because a triplicate CV > 20.0% was observed in the undiluted sample, the first twofold dilution result was used as a reference to calculate the bias.
  4. aValue just below the LLOQP of 1.57 pg/mL included in statistics.
  5. Italic bold: result outside 70–130% recovery, or absolute bias > 30%.
  6. Conc., concentration; CSF, cerebrospinal fluid; CV, coefficient of variation; HD, Huntington’s disease; LLOQp, parallelism lower limit of quantification; mHTT, mutant huntingtin protein; NA, not applicable; NV, no value, duplicate well CV > 20%; polyQ, polyglutamine.
  7. Cross-lab difference (%) = (Result ICON—Result Roche) / (Result ICON + Result Roche)/2) *100.
Back to article page