Proinflammatory Cytokines in Blood From Children With Seizures: Preliminary Results of a Cross-Sectional Study
Abstract number :
3.087
Submission category :
2. Translational Research / 2C. Biomarkers
Year :
2018
Submission ID :
501589
Source :
www.aesnet.org
Presentation date :
12/3/2018 1:55:12 PM
Published date :
Nov 5, 2018, 18:00 PM
Authors :
Luca Bartolini, National Institutes of Health; Michael Moran, National Institutes of Health; Emily Leibovitch, National Institutes of Health; Bobbe Thomas, Children's National Medical Center; Alexander Dick, Children's National Medical Center; Elizabeth W
Rationale: Experimental and clinical findings suggest a pivotal role of inflammation in epileptogenesis, which may be triggered by HHV6 infection.We aimed to analyze levels of inflammatory cytokines in plasma from children with acute seizures compared to healthy children and assess a correlation with HHV6. Methods: We analyzed plasma from 36 children within 24 hours of acute seizures (cases) and 43 healthy children (controls) with a multiplex electrochemiluminescence assay for neuroinflammatory cytokines including: Interferon (IFN)-?, Interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, Tumor Necrosis Factor (TNF)-a, Chemokine C-C motif ligand (CCL)-2, CCL-3, CCL-4, CCL-11, CCL-17, CCL-26, C-X-C motif chemokine 10 (CXCL10). Saliva from all controls and 6 cases and blood from 26 controls and 16 cases were analyzed by droplet digital PCR for HHV6 and EBV viral DNA. Statistical analysis included Wilcoxon Rank Sum test and Spearman correlation. Results: Cases included first unprovoked seizure (n=14; group I), acute seizures in chronic epilepsy (n=18; group II) and febrile seizures (n=4; group III). We observed higher levels (pg/mL) of IL-8 in plasma from group II compared to controls (Median [Mdn] 12.0 vs. 9.6; p=0.03). This group also had higher levels of CCL-11 (Mdn 340.4 vs. 145.2; p=0.0007) and CCL-26 (Mdn 98.9 vs. 46.3; p<0.0001).We also observed higher levels of IFN-? (Mdn 278.7 vs. 10.5; p<0.0001) and IL-6 (Mdn 28.6 vs. 1.2; p<0.0001) in group III, and a mild correlation IFN-? (plasma)/viral load (saliva) for HHV6 positive controls and cases (r=0.4; p=0.04). We found higher levels of CCL-11 (Mdn 264.3 Vs. 145.2; p=0.03) and CCL-26 (Mdn 70.0 vs. 46.3; p=0.01) in group I and also higher levels of IL-6 (Mdn 2.7 vs. 1.1; p=0.005).Saliva from 29/43 controls (67%) was positive for HHV6 vs. 1/6 tested (17%) cases (from group I) and 10/43 (15%) tested positive for EBV vs. 3/6 (50%) cases. Similar HHV6 DNA detection in blood was seen in controls (4/26, 15%) vs. group II (1/8, 13%), but markedly low frequency was observed in tested cases as a whole (1/16, 6%). Controls also had a higher detection of EBV (4/26, 15%) vs. none in cases. Conclusions: Different cytokines may have a role in specific inflammatory cascades involved in the onset of acute seizures for specific subsets of patients, and HHV6 infection may represent a common trigger for activation of robust upstream response of IFN-?.Both children with first unprovoked seizures and children with epilepsy presenting with breakthrough seizures showed increased levels of CCL-11 and CCL-26, a family of cytokines that may decrease hippocampal neurogenesis and serve as mediators in epileptogenesis. Preliminary PCR data showed higher HHV6 detection in blood and saliva from healthy children compared to cases. Controls may harbor a latent infection with no pathogenic response, as opposed to cases, where the virus may be “sequestered” in the CNS (and therefore be less detectable in the periphery) and trigger an inflammatory response eventually leading to seizure generation. Funding: Dr. Bartolini reports receiving grant support from the American Epilepsy Society / Epilepsy Foundation of America (Research Training Fellowship for Clinicians).