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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Molecular Autism 1/2014

Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome

Zeitschrift:
Molecular Autism > Ausgabe 1/2014
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​2040-2392-5-4) contains supplementary material, which is available to authorized users.

Competing interests

SB and JDC are consultants for Myriad-RBM. This does not affect policies regarding sharing of data and materials specified by this journal.

Authors’ contributions

HS, JMR, PS and JDC carried out the molecular profiling data analyses. PCG, SB and SB-C interpreted the results, prepared the figures and tables, and wrote the manuscript. LR, SB, HR and SB-C designed the clinical studies and edited the manuscript. EI, LR, and BA coordinated clinical data collection. SB and SB-C conceived the study, interpreted the results and edited the manuscript. All authors read and approved the final manuscript.

Abstract

Background

The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum.

Methods

Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS.

Results

Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls.

Conclusion

Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches.
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