Table 3.

Comparison of host immune and inflammatory response to P falciparum in children with severe anemia and P falciparum parasitemia by sickle cell genotype

Cell biomarker	HbSS, Median (IQR), n = 22	HbAA, Median (IQR), n = 208	P*,†	β coefficient‡ (95% CI), adjusted for age	P †
Markers of inflammation
C-reactive protein, mg/dL	25.0 (16.7, 34.5)	44.0 (25.2, 64.7) (n = 192)	<.001	−0.2 (−0.4, 0.0)	.03
α-1 glycoprotein, μcg/mL	1350 (1048, 1887) (n = 19)	2128 (1726, 2601) (n = 170)	<.001	−0.2 (−0.2, −0.1)	<.001
Plasma concentrations of pro- and anti-inflammatory cytokines and chemokines
G-CSF, pg/mL	39.8 (17.3, 74.1) (n = 19)	60.0 (37.4, 102.3) (n = 172)	.02	−0.2 (−0.4, 0.0)	.10
Interferon-γ, pg/mL	115 (67.9, 178) (n = 19)	91.7 (57.5, 158) (n = 172)	.29	0.1 (−0.2, 0.3)	.60
IL-1β, pg/mL	2.5 (0.5, 4.4) (n = 19)	2.9 (1.9, 4.1) (n = 172)	.75	−0.1 (−0.3, 0.1)	.38
IL-1 receptor α, pg/mL	506 (263, 811) (n = 19)	607 (323, 1610) (n = 172)	.12	−0.1 (−0.4, 0.1)	.40
IL-4, pg/mL	2.8 (1.3, 6.0) (n = 19)	2.5 (1.1, 4.4) (n = 172)	.60	0.0 (−0.3, 0.3)	.96
IL-6, pg/mL	36.8 (5.4, 68.9) (n = 21)	40.2 (13.7, 105) (n = 195)	.39	−0.2 (−0.5, 0.2)	.36
IL-8, pg/mL	22.9 (15.8, 37.0) (n = 19)	30.5 (19.8, 44.9) (n = 172)	.14	−0.1 (−0.3, 0.1)	.29
IL-10, pg/mL	53.7 (16.2, 118) (n = 19)	102 (35.3, 263) (n = 172)	.05	−0.2 (−0.5, 0.2)	.27
IL-12 p70, pg/mL	17.5 (9.8, 26.3) (n = 19)	22.2 (13.3, 35.8) (n = 172)	.11	−0.1 (−0.4, 0.1)	.23
MCP-1, pg/mL	15.4 (11.1, 25.8) (n = 19)	33.4 (18.2, 87.9) (n = 172)	<.001	−0.4 (−0.7, −0.1)	.02
MIP-1α, pg/mL	6.7 (4.1, 11) (n = 19)	6.4 (4.2, 10) (n = 172)	.90	0.0 (−0.3, 0.2)	.75
MIP-1β, pg/mL	181 (71.9, 313) (n = 19)	285 (184, 425) (n = 172)	.004	−0.2 (−0.4, −0.1)	<.001
Platelet factor 4 (platelet-free plasma), ng/mL	878 (381, 2100) (n = 19)	709 (318, 1530) (n = 166)	.20	0.2 (−0.1, 0.5)	.14
RANTES, pg/mL	3790 (1530, 5470) (n = 19)	3480 (1750, 6860) (n = 172)	.61	−0.1 (−0.3, 0.1)	.48
TNF-α, pg/mL	41.7 (21.5, 64.1) (n = 21)	87.6 (51.1, 141) (n = 195)	<.001	−0.3 (−0.6, −0.1)	.006
Plasma concentrations of markers of endothelial activation
VWF, % of normal	104 (72.6, 198) (n = 19)	137 (69.2, 239) (n = 146)	.29	−0.1 (−0.3, 0.1)	.41
sVCAM-1, ng/mL	3050 (2070, 5720) (n = 19)	3260 (2550, 4800) (n = 171)	.51	0.0 (−0.1, 0.1)	.78
sICAM-1, ng/mL	370 (230, 1230) (n = 19)	727 (300, 1400) (n = 172)	.20	0.0 (−0.4, 0.3)	.84
sE-selectin, ng/mL	184 (117, 245) (n = 19)	190 (135, 258) (n = 172)	.88	0.0 (−0.1, 0.1)	.54
P-selectin, ng/mL	58.3 (47.9, 85.8) (n = 9)	45.1 (35.4, 66.3) (n = 99)	.22	0.1 (−0.1, 0.3)	.23
sEPCR, ng/mL	68.9 (60.1, 102) (n = 20)	97.2 (72.5, 250) (n = 187)	.02	−0.1 (−0.2, 0.00)	.06
Plasma concentrations of markers of angiogenesis
Angpt-1, ng/mL	5.4 (2.8, 7.6) (n = 18)	4.2 (1.8, 7.5) (n = 172)	.28	0.2 (−0.1, 0.4)	.24
Angpt-2, ng/mL	5.0 (3.6, 6.7) (n = 18)	1.7 (0.9, 2.8) (n = 172)	<.001	0.3 (0.1, 0.5)	.01
VEGF, pg/mL	45.0 (24.3, 138) (n = 19)	62.3 (34.1, 93.6) (n = 172)	.67	0.0 (−0.2, 0.2)	.92
PDGF-bb, pg/mL	2080 (617, 2930) (n = 19)	899 (446, 1730) (n = 172)	.04	0.2 (0.0, 0.5)	.04
Plasma concentrations of NO and regulators
NO concentration, μmol/L	44.1 (31.4, 87.6) (n = 18)	53.1 (31.7, 90.6) (n = 164)	.88	0.0 (−0.2, 0.2)	.59
ADMA, μmol/L	0.9 (0.7, 1.1) (n = 22)	0.7 (0.6, 0.9) (n = 204)	.005	0.07 (0.0, 0.1)	.06
l-arginine, µmol/L	20 (20, 30) (n = 18)	30 (20, 30) (n = 153)	.05	−0.1 (−0.2, 0.0)	.007
l-arginine/ADMA§	24.2 (21.6, 30.3) (n = 18)	34.7 (25.9, 47.6) (n = 149)	.002	−13.5 (−22.6, −4.4)	.004

For tests that did not include all participants, the n is listed next to the result.

^*Determined by use of Wilcoxon rank-sum test.

^†Significant P values in bold, determined by FDR = 0.05 correction for multiple comparisons.

^‡Denotes linear regression β coefficient for log10-transformed values, adjusted for age.

^§Denotes linear regression performed using non-transformed values.