Abstract
Our previous research has shown that purified peripheral blood monocytes (PRMo) from individuals who are diagnosed with autism spectrum disorders (ASDs) and have innate immune abnormalities reveal altered interleukin-1ß (IL-1ß)/IL-10 ratios. We also found, in separate studies, that microRNA (miRNA) expression in PBMo and mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) differed in the IL-1ß/IL-10-based ASD subgroups. This study explored whether serum miRNAs are associated with both altered innate immune responses and changes in mitochondrial respiration as a link of regulatory mechanisms for these two common abnormalities in ASD subjects. Serum miRNA levels were examined by high-throughput deep sequencing in ASD and non-ASD control sera with concurrent measurement of PBMo cytokine production and mitochondrial respiration by PBMCs. ASD samples were examined as a whole group and with respect to the previously defined IL-1ß/IL-10-based ASD subgroups (high, normal, and low groups). Serum miRNA levels differed between the overall ASD sera (N = 116) and non-ASD control sera (N = 35) and also differed across the IL-1ß/IL-10-based ASD subgroups. Specifically, miRNA levels were increased and decreased in eight and nine miRNAs, respectively, in the high-ratio ASD subgroup (N = 48). In contrast, the low- (N = 25) and normal- (N = 43) ratio ASD subgroups only showed decreased miRNAs levels (18 and 10 miRNAs, respectively). Gene targets of the altered miRNAs in the high and/or low IL-1β/IL-10 ratio ASD subgroups were enriched in pathways critical for monocyte functions and metabolic regulation. Gene targets of the altered miRNAs in all the ASD subgroups were enriched in pathways of neuronal development and synaptic plasticity, along with cell proliferation/differentiation. ASD subgroup-specific associations were observed between serum miRNA expression and IL-1ß/IL-10 ratios, mitochondrial respiration, and monocyte cytokine profiles (IL-10, CCL2, and TNF-α). In summary, our results indicate that serum levels of select miRNAs may serve as promising biomarkers for screening and monitoring changes in innate immunity and mitochondrial respiration in ASD.
Highlights
Repeated genetic studies suggest that only about 10–20% of individuals with autism spectrum disorder (ASD) have a welldefined gene mutation [1]
We found altered correlations between serum miRNA levels and monocyte cytokine profiles and mitochondrial respiration across the IL-1ß/IL-10-based ASD subgroups
These results are consistent with our finding that genes targeted by miRNAs that showed differences in serum levels from non-ASD controls are associated with pathways, crucial for monocyte functions and metabolic regulation in the high and low IL-1ß/IL-10 ratio ASD subgroups
Summary
Repeated genetic studies suggest that only about 10–20% of individuals with autism spectrum disorder (ASD) have a welldefined gene mutation [1]. The etiology of ASD, in the great majority of patients, is believed to be due to complex interactions of genetic and environmental factors during critical periods of brain development. Given the diverse effects of such genetic and environmental factors, it is not surprising that disease outcome and therapeutic options are highly heterogeneous in ASD population. There are few objective biomarker(s) useful for assessing clinical outcomes, responses to intervention measures, and/or the underlying effects of genetic/environmental factors in ASD. Many individuals with ASD do not respond well to the first-line behavioral and pharmacological interventions. The identification of objective biomarkers will be especially important for such poor responders
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
