Immune transcriptome alterations in the temporal cortex of subjects with autism.
Autism is a severe disorder that involves both genetic and environmental factors. Expression profiling of the superior temporal gyrus of six autistic subjects and matched controls revealed increased transcript levels of many immune system-related genes. We also noticed changes in transcripts related to cell communication, differentiation, cell cycle regulation and chaperone systems. Critical expression changes were confirmed by qPCR (BCL6, CHI3L1, CYR61, IFI16, IFITM3, MAP2K3, PTDSR, RFX4, SPP1, RELN, NOTCH2, RIT1, SFN, GADD45B, HSPA6, HSPB8 and SERPINH1). Overall, these expression patterns appear to be more associated with the late recovery phase of autoimmune brain disorders, than with the innate immune response characteristic of neurodegenerative diseases. Moreover, a variance-based analysis revealed much greater transcript variability in brains from autistic subjects compared to the control group, suggesting that these genes may represent autism susceptibility genes and should be assessed in follow-up genetic studies.
Garbett
Krassimira
K
Department of Psychiatry, Vanderbilt University, Nashville, USA.
Ebert
Philip J
PJ
Department of Psychiatry, Vanderbilt University, Nashville, USA.
Mitchell
Amanda
A
Department of Psychiatry, Vanderbilt University, Nashville, USA.
Lintas
Carla
C
Laboratory of Molecular Psychiatry and Neurogenetics, University "Campus Bio-Medico", Rome, Italy; Laboratory of Molecular Psychiatry and Psychiatric Genetics, Department of Experimental Neurosciences, I.R.C.C.S. "Fondazione Santa Lucia", Rome, Italy.
Manzi
Barbara
B
Department of Child Neuropsychiatry, University "Tor Vergata", Rome, Italy.
Mirnics
Károly
K
Department of Psychiatry, Vanderbilt University, Nashville, USA; Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, USA. Electronic address: karoly.mirnics@vanderbilt.edu.
Persico
Antonio M
AM
Laboratory of Molecular Psychiatry and Neurogenetics, University "Campus Bio-Medico", Rome, Italy; Laboratory of Molecular Psychiatry and Psychiatric Genetics, Department of Experimental Neurosciences, I.R.C.C.S. "Fondazione Santa Lucia", Rome, Italy. Electronic address: a.persico@unicampus.it.
D000328:Adult; D001321:Autistic Disorder / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000091042:Reelin Protein; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013702:Temporal Lobe / Q000276:immunology* / Q000473:pathology / Q000502:physiology
D016207:Cytokines; D000091042:Reelin Protein; C000717127:RELN protein, human