Abstract
Background and Purpose-Deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology can be challenging. Ischemia of cerebral tissue elicits an immune response in stroke and transient ischemic attack (TIA). This response, as detected by RNA expressed in immune cells, could potentially distinguish ischemic from nonischemic TNE. Methods-Analysis of 208 TIAs, ischemic strokes, controls, and TNE was performed. RNA from blood was processed on microarrays. TIAs (n=26) and ischemic strokes (n=94) were compared with controls (n=44) to identify differentially expressed genes (false discovery rate <0.05, fold change ≥1.2). Genes common to TIA and stroke were used predict ischemia in TIA diffusion-weighted imaging-positive/minor stroke (n=17), nonischemic TNE (n=13), and TNE of unclear etiology (n=14). Results-Seventy-four genes expressed in TIA were common to those in ischemic stroke. Functional pathways common to TIA and stroke related to activation of innate and adaptive immune systems, involving granulocytes and B cells. A prediction model using 26 of the 74 ischemia genes distinguished TIA and stroke subjects from control subjects with 89% sensitivity and specificity. In the validation cohort, 17 of 17 TIA diffusion-weighted imaging-positive/minor strokes were predicted to be ischemic, and 10 of 13 nonischemic TNE were predicted to be nonischemic. In TNE of unclear etiology, 71% were predicted to be ischemic. These subjects had higher ABCD scores. Conclusions-A common molecular response to ischemia in TIA and stroke was identified, relating to activation of innate and adaptive immune systems. TNE of ischemic etiology was identified based on gene profiles that may be of clinical use once validated.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1006-1012 |
| Number of pages | 7 |
| Journal | Stroke |
| Volume | 43 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2012 |
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Keywords
- gene expression
- immune response
- ischemia
- ischemic stroke
- TIA
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Clinical Neurology
- Advanced and Specialized Nursing
Cite this
Ischemic transient neurological events identified by immune response to cerebral ischemia. / Jickling, Glen C.; Zhan, Xinhua; Stamova, Boryana; Ander, Bradley; Tian, Yingfang; Liu, Da; Sison, Shara Mae; Verro, Piero; Johnston, S. Claiborne; Sharp, Frank R.
In: Stroke, Vol. 43, No. 4, 04.2012, p. 1006-1012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ischemic transient neurological events identified by immune response to cerebral ischemia
AU - Jickling, Glen C.
AU - Zhan, Xinhua
AU - Stamova, Boryana
AU - Ander, Bradley
AU - Tian, Yingfang
AU - Liu, Da
AU - Sison, Shara Mae
AU - Verro, Piero
AU - Johnston, S. Claiborne
AU - Sharp, Frank R
PY - 2012/4
Y1 - 2012/4
N2 - Background and Purpose-Deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology can be challenging. Ischemia of cerebral tissue elicits an immune response in stroke and transient ischemic attack (TIA). This response, as detected by RNA expressed in immune cells, could potentially distinguish ischemic from nonischemic TNE. Methods-Analysis of 208 TIAs, ischemic strokes, controls, and TNE was performed. RNA from blood was processed on microarrays. TIAs (n=26) and ischemic strokes (n=94) were compared with controls (n=44) to identify differentially expressed genes (false discovery rate <0.05, fold change ≥1.2). Genes common to TIA and stroke were used predict ischemia in TIA diffusion-weighted imaging-positive/minor stroke (n=17), nonischemic TNE (n=13), and TNE of unclear etiology (n=14). Results-Seventy-four genes expressed in TIA were common to those in ischemic stroke. Functional pathways common to TIA and stroke related to activation of innate and adaptive immune systems, involving granulocytes and B cells. A prediction model using 26 of the 74 ischemia genes distinguished TIA and stroke subjects from control subjects with 89% sensitivity and specificity. In the validation cohort, 17 of 17 TIA diffusion-weighted imaging-positive/minor strokes were predicted to be ischemic, and 10 of 13 nonischemic TNE were predicted to be nonischemic. In TNE of unclear etiology, 71% were predicted to be ischemic. These subjects had higher ABCD scores. Conclusions-A common molecular response to ischemia in TIA and stroke was identified, relating to activation of innate and adaptive immune systems. TNE of ischemic etiology was identified based on gene profiles that may be of clinical use once validated.
AB - Background and Purpose-Deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology can be challenging. Ischemia of cerebral tissue elicits an immune response in stroke and transient ischemic attack (TIA). This response, as detected by RNA expressed in immune cells, could potentially distinguish ischemic from nonischemic TNE. Methods-Analysis of 208 TIAs, ischemic strokes, controls, and TNE was performed. RNA from blood was processed on microarrays. TIAs (n=26) and ischemic strokes (n=94) were compared with controls (n=44) to identify differentially expressed genes (false discovery rate <0.05, fold change ≥1.2). Genes common to TIA and stroke were used predict ischemia in TIA diffusion-weighted imaging-positive/minor stroke (n=17), nonischemic TNE (n=13), and TNE of unclear etiology (n=14). Results-Seventy-four genes expressed in TIA were common to those in ischemic stroke. Functional pathways common to TIA and stroke related to activation of innate and adaptive immune systems, involving granulocytes and B cells. A prediction model using 26 of the 74 ischemia genes distinguished TIA and stroke subjects from control subjects with 89% sensitivity and specificity. In the validation cohort, 17 of 17 TIA diffusion-weighted imaging-positive/minor strokes were predicted to be ischemic, and 10 of 13 nonischemic TNE were predicted to be nonischemic. In TNE of unclear etiology, 71% were predicted to be ischemic. These subjects had higher ABCD scores. Conclusions-A common molecular response to ischemia in TIA and stroke was identified, relating to activation of innate and adaptive immune systems. TNE of ischemic etiology was identified based on gene profiles that may be of clinical use once validated.
KW - gene expression
KW - immune response
KW - ischemia
KW - ischemic stroke
KW - TIA
UR - http://www.scopus.com/inward/record.url?scp=84859372152&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859372152&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.111.638577
DO - 10.1161/STROKEAHA.111.638577
M3 - Article
C2 - 22308247
AN - SCOPUS:84859372152
VL - 43
SP - 1006
EP - 1012
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 4
ER -