Plasma interleukin-1beta concentration is associated with stroke in sickle cell disease

Abstract

The pathogenesis of sickle cell disease (HbSS), which has numerous complications including stroke, involves inflammation resulting in alteration of plasma inflammatory protein concentration. We investigated HbSS children with abnormal cerebral blood flow detected by trans-cranial Doppler ultrasound (TCD) who participated in the multi-center stroke prevention (STOP) study, to determine if plasma inflammatory protein concentration is associated with the outcome of stroke. Thirty-nine plasma samples from HbSS participants with elevated TCD who had no stroke, HbSS-NS (n=13) or had stroke, HbSS-S (n=13), HbSS steady-state controls (n=7) and controls with normal hemoglobin, HbAA (n=6), were analyzed simultaneously for 27 circulating inflammatory proteins. Logistic regression and receiver operating characteristics curve analysis of stroke on plasma inflammatory mediator concentration, adjusted for age and gender, demonstrated that interleukin-1beta (IL-1beta) was protective against stroke development (HbSS-NS=19, 17-23, HbSS-S=17, 16-19 pg/mL, median and 25th-75th percentile; odds ratio=0.59, C.I.=0.36-0.96) and was a good predictor of stroke (area under curve=0.852). This result demonstrates a strong association of systemic inflammation with stroke development in HbSS via moderately increased plasma IL-1beta concentration, which is furthermore associated with a decreased likelihood of stroke in HbSS.

Figure 1

Comparison of circulating IL-1β for HbAA controls, HbSS steady-state controls, HbSS-NS STOP study subjects with no stroke and HbSS-S STOP study subjects who developed stroke. Values are median plus 25^th and 75^th percentiles, bars represent 10^th and 90^th percentiles and points represent values outside of the 10^th and 90^th percentiles. Using Dunn’s Method for pair-wise comparison there was no statistically significant difference in the median concentration of IL-1β between the groups.

Figure 2

Receiver operating characteristics curve of stroke on plasma IL-1β concentration, adjusted for age and gender. This ROC curve shows that IL-1β is a good biomarker for predicting the likelihood of stroke development in HbSS individuals with abnormal cerebral blood flow determined by TCD. The area under the ROC curve of 0.85 is good, since 1.00 is the maximum attainable by an ideal biomarker