Table 2 Inflammation, endothelial activation, neuronal damage and coagulation markers in HIV-infected and uninfected children.

From: Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV

MARKER

HIV-infected children

Uninfected controls

P-value

CSF (HIV-infected)

CONCORDANCE

Acute phase reactants

median (IQR)

median (IQR)

unadjusted

with FDR

median (IQR)

Kendall’s W (CI)

C-reactive protein

0.71 (0.30–2.48)a

0.28 (0.16–0.81)a

0.004*

0.035*

2.38 (0.91–8.40)

0.99 (0.95–0.99)

Serum amyloid A

1.26 (0.65–2.85)b

1.01 (0.37–1.72)b

0.13

0.51

—

—

Interleukins

Interleukin-5

0.63 (0.46–0.97)

0.72 (0.54–0.95)

0.70

0.84

—

—

Interleukin-6

—

—

—

—

0.66 (0.53–0.84)

—

Interleukin-7

3.4 (2.3–4.7)

3.0 (1.6–4.6)

0.36

0.75

0.55 (0.29–1.02)

0.46 (0.23–0.68)

Interleukin-8

2.2 (1.5–3.2)

2.3 (1.5–3.3)

0.77

0.85

22.9 (15.6–27.8)

0.27 (0.13–0.46)

Interleukin-10

0.25 (0.19–0.41)

0.25 (0.18–0.31)

0.62

0.84

0.19 (0.10–0.38)

0.40 (0.23–0.60)

Interleukin-12 subunit p40

181 (117–232)

151 (123–203)

0.63

0.84

3.7 (2.3–20.9)

0.49 (0.25–0.76)

Interleukin-15

1.6 (1.0–2.0)

1.1 (0.9–1.6)

0.015*

0.10

1.1 (0.9–1.7)

0.52 (0.30–0.75)

Interleukin-16

175 (146–226)

189 (158–265)

0.20

0.57

—

—

Cytokines

Tumor necrosis factor-alpha

2.3 (1.8–3.3)

2 (1.7–2.4)

0.070

0.32

—

—

Interferon-gamma

9.6 (6.9–14.4)

5.7 (4.2–8.7)

0.001*

0.021*

2.29 (1.73–4.20)

0.62 (0.42–0.78)

Chemokines

Interferon-gamma-inducible protein 10

340 (239–603)

250 (169–314)

0.004*

0.035*

222 (93–275)

0.49 (0.25–0.74)

Monocyte chemoattractant protein-1

99 (77–123)

72 (57–90)

<0.001*

0.004*

225.1 (0.2–347.1)

0.46 (0.25–0.68)

Monocyte chemoattractant protein-4

50 (35–60)

46 (28–54)

0.24

0.57

—

—

Macrophage-derived chemokine

1273 (1019–1599)

1221 (1034–1722)

0.71

0.84

12.8 (8.4–19)

0.54 (0.31–0.74)

Thymus and activation regulated chemokine

90 (49–203)

91 (55–163)

0.89

0.93

2.7 (1.8–5.2)

0.59 (0.36–0.77)

Macrophage inflammatory protein 1-alpha

—

—

—

—

8.9 (5.3–13.1)

—

Macrophage inflammatory protein 1-beta

49 (38–77)

49 (41–71)

0.64

0.84

12 (9.9–14.3)

0.71 (0.48–0.87)

Eosinophil chemotactic protein

63 (45–87)

56 (37–74)

0.16

0.51

11.3 (5.9–20.3)

0.36 (0.22–0.52)

Monocyte activation

Soluble cluster of differentiation 14 c

1925 (1551–2583)

1861 (1131–2484)

0.26

0.58

42 (30–72)

0.56 (0.34–0.76)

Soluble cluster of differentiation 163 c

216 (150–293)

206 (171–276)

>0.99

>0.99

12.5 (8.6–19.1)

0.50 (0.27–0.74)

Endothelial activation

Soluble vascular cell adhesion molecule-1 c

472 (401–538)

438 (390–503)

0.027*

0.14

0.28 (0.20–0.37)

0.78 (0.58–0.90)

Soluble intercellular adhesion molecule-1 c

639 (525–838)

591 (437–668)

0.22

0.57

0.71 (0.55–1.23)

0.78 (0.58–0.92)

Vascular growth factors

Vascular endothelial growth factor A

40 (27–67)

50 (35–94)

0.15

0.51

—

—

Vascular endothelial growth factor C

81 (61–183)

100 (70–157)

0.42

0.77

—

—

Vascular endothelial growth factor D

430 (360–511)

415 (372–504)

0.74

0.84

  

Basic fibroblast growth factor

2.7 (1.4–10.7)

3 (1.2–5.1)

0.47

0.81

0.36 (0.11–0.99)

0.32 (0.18–0.61)

FMS-like tyrosine kinase-1 (VEGF receptor-1)

72 (59–85)

74 (63–90)

0.66

0.84

31 (25–41)

0.54 (0.32–0.74)

Tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Angiopoietin-1 receptor)

4930 (4636–5689)

5267 (4673–5824)

0.50

0.81

16 (14–24)

0.65 (0.42–0.83)

Coagulation

D-dimer

0.3 (0.2–0.5)

0.2 (0.2–0.3)

0.23

0.57

—

—

Von Willebrand factor antigen

109 (86–148)

107 (87–138)

0.61

0.84

—

—

Von Willebrand factor propeptide

97 (84–115)

101 (89–115)

0.69

0.84

—

—

Thrombin-antithrombin complex

3.5 (3.1–4.3)

3.5 (3.1–4.2)

0.90

0.93

—

—

Prothrombin fragment 1 + 2

126 (108–153)

115 (101–151)

0.39

0.75

—

—

Neuronal injury

Neurofilament heavy chain

—

—

—

—

124 (99–149)

—

Total Tau protein

—

—

—

—

158 (102–235)

—

  1. Plasma and CSF concentrations are displayed as median (interquartile range) in pg/ml, unless specified otherwise. Coagulation biomarkers were only measured in plasma, and neuronal markers NFH and Tau only in CSF. Markers were excluded from analysis when less than 70% of measurements fell within the range of quantification (as specified in the Supplemental Methods). Plasma markers were compared between HIV-infected children (n = 34) and uninfected controls (n = 37) using the Mann-Whitney-U test, and P-values are displayed before and after multiplicity correction by FDR control. Concordance between plasma and CSF levels (sCD14/sCD163 n = 25, other biomarkers n = 23) in the HIV-infected group was assessed using Kendall’s coefficient of concordance (Kendall’s W).
  2. Definitions: HIV = human immunodeficiency virus; CSF = cerebrospinal fluid; FDR = False Discovery Rate; Kendall’s W = Kendall’s coefficient of concordance; CI = bootstrap confidence interval. amg/l; bµg/l; cng/ml; *P-value < 0.05.
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