|
|
|
|
Differential expression of interferon-γ and chemokine genes distinguishes Rasmussen encephalitis from cortical dysplasia and provides evidence for an early Th1 immune response
|
|
|
|
|
|
|
|
نویسنده
|
owens g.c. ,huynh m.n. ,chang j.w. ,mcarthur d.l. ,hickey m.j. ,vinters h.v. ,mathern g.w. ,kruse c.a.
|
|
منبع
|
journal of neuroinflammation - 2013 - دوره : 10 - شماره : 0
|
|
چکیده
|
Background: rasmussen encephalitis (re) is a rare complex inflammatory disease,primarily seen in young children,that is characterized by severe partial seizures and brain atrophy. surgery is currently the only effective treatment option. to identify genes specifically associated with the immunopathology in re,rna transcripts of genes involved in inflammation and autoimmunity were measured in brain tissue from re surgeries and compared with those in surgical specimens of cortical dysplasia (cd),a major cause of intractable pediatric epilepsy.methods: quantitative polymerase chain reactions measured the relative expression of 84 genes related to inflammation and autoimmunity in 12 re specimens and in the reference group of 12 cd surgical specimens. data were analyzed by consensus clustering using the entire dataset,and by pairwise comparison of gene expression levels between the re and cd cohorts using the harrell-davis distribution-free quantile estimator method.results: consensus clustering identified six re cases that were clearly distinguished from the cd cases and from other re cases. pairwise comparison showed that seven mrnas encoding interferon-γ,ccl5,ccl22,ccl23,cxcl9,cxcl10,and fas ligand were higher in the re specimens compared with the cd specimens,whereas the mrna encoding hypoxanthine-guanine phosphoribosyltransferase was reduced. interferon-γ,cxcl5,cxcl9 and cxcl10 mrna levels negatively correlated with time from seizure onset to surgery (p <0.05),whereas ccl23 and fas ligand transcript levels positively correlated with the degree of tissue destruction and inflammation,respectively (p <0.05),as determined from magnetic resonance imaging (mri) t2 and flair images. accumulation of cd4+ lymphocytes in leptomeninges and perivascular spaces was a prominent feature in re specimens resected within a year of seizure onset.conclusions: active disease is characterized by a th1 immune response that appears to involve both cd8+ and cd4+ t cells. our findings suggest therapeutic intervention targeting specific chemokine/chemokine receptors may be useful in early stage re. © 2013 owens et al.; licensee biomed central ltd.
|
|
کلیدواژه
|
Chemokines; Cortical dysplasia; Epilepsy; Gene expression; Inflammation; Rasmussen encephalitis; T cells
|
|
آدرس
|
department of neurosurgery,david geffen school of medicine,university of california,los angeles,ca,united states,ucla neurosurgery,gonda center,box 951761,los angeles,ca 90095, United States, department of neurosurgery,david geffen school of medicine,university of california,los angeles,ca, United States, department of neurosurgery,david geffen school of medicine,university of california,los angeles,ca, United States, department of neurosurgery,david geffen school of medicine,university of california,los angeles,ca, United States, department of pathology and laboratory medicine,david geffen school of medicine,university of california,los angeles,ca, United States, department of pathology and laboratory medicine,david geffen school of medicine,university of california,los angeles,ca,united states,department of neurology,david geffen school of medicine,university of california,los angeles,ca, United States, department of neurosurgery,david geffen school of medicine,university of california,los angeles,ca,united states,intellectual and developmental disabilities research center,david geffen school of medicine,university of california,los angeles,ca,united states,mattel children's hospital,david geffen school of medicine,university of california,los angeles,ca,united states,brain research institute,david geffen school of medicine,university of california,los angeles,ca, United States, department of neurosurgery,david geffen school of medicine,university of california,los angeles,ca,united states,brain research institute,david geffen school of medicine,university of california,los angeles,ca, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|