Immune transcriptome alterations in the temporal cortex of subjects with autism

Abstract

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.

Involvement of the PRKCB1 gene in autistic disorder: significant genetic association and reduced neocortical gene expression

“…54,55 These proinflammatory effects of PKCb sharply contrast with the decrease in PRKCB1 gene expression reported here, because the very same neocortical brain samples employed in this study display enhanced oxidative stress (L Palmieri, AM Persico et al, submitted) and increased immune gene expression. 56 The latter results are in agreement with previous studies demonstrating enhanced oxidative stress in autism 57 and an ongoing immune reaction in a set of postmortem brain tissue samples of autistic patients largely non-overlapping with ours, and in the CSF of autistic children collected in vivo. 58 …”

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

“…According to post-mortem and in vivo studies, an ongoing immune response could provide such a contribution by raising intracellular Ca 2 þ levels through cytokines, such as tumor necrosis factor-a and receptors, like CD38. 28,47,48 Indeed, the existence of an immune dysreactivity is also supported by the association between macrocephaly and macrosomy in autism with a history of immune/ allergic disorders, either in the patient or in his/her first-degree relatives. 9 Immune mechanisms may also mediate the vulnerability to autism conferred by recently described 16p11.2 microdeletions.…”

“…The same, or slightly larger paired patient-control samples, have been the object of recent reports. [26][27][28] Brain tissue processing Fresh frozen brain tissue samples dissected from the superior temporal gyrus (BA 41/42 or 22) of patients and controls were obtained through the Autism Tissue Program from the NICHD Brain and Tissue Bank and the Harvard Brain Tissue Resource Center. Cortical gray matter (100-200 mg) was suspended in a buffer containing 250 mM sucrose and 10 mM TRIS, pH 7.4 and homogenated using a Teflon glass potter.…”

Endocannabinoid Signaling in Autism

“…In between these extremes, ASD for most cases fully qualifies for the definition of a Bcomplex^disorder, whereby a host of rare and common genetic variants, often but not necessarily in conjunction with epigenetic factors [63], yield the neurodevelopmental abnormalities summarized above, resulting in autistic behaviors. Finally, neuroinflammation is also a frequent finding in postmortem brains of autistic individuals [64,65]. It may represent a nonspecific consequence of insufficient neurite pruning and abnormal wiring of neural networks, resulting in elevated oxidative stress (possibly a common feature shared by several neurodevelopmental disorders) [66], but it could also stem from a broader immune dysfunction which, together with gastrointestinal disturbances and recurrent infections, collectively qualifies ASD as a systemic disorder [67][68][69][70][71].…”