Department of Chemical Engineering & Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, UK.
Mol Autism. 2014 Jan 27;5(1):4. doi: 10.1186/2040-2392-5-4.
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.
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.
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.
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.
多年来，人们已经知道，男性中阿斯伯格综合征（AS）和其他自闭症谱系障碍的患病率更高。然而，最近的多重免疫分析谱研究表明，患有 AS 的男性和女性的血清中有明显不同的蛋白质组变化。
在这里，我们使用多重免疫分析和无标记液相色谱-质谱联用（LC-MS）分析了在采集样本时未服用药物的成年 AS 患者（男性 14 例，女性 16 例）和对照者（男性 13 例，女性 16 例）的血清。主要目的是确定与 AS 相关的性别特异性血清蛋白变化。
多重免疫分析谱分析导致鉴定出 16 种蛋白质，这些蛋白质在 AS 个体中以性别特异性的方式显著改变。其中 3 种在女性中改变（ADIPO、IgA、APOA1），7 种在男性中改变（BMP6、CTGF、ICAM1、IL-12p70、IL-16、TF、TNF-alpha），6 种在两性中改变但方向相反（CHGA、EPO、IL-3、TENA、PAP、SHBG）。无标记 LC-MS 谱分析导致鉴定出 13 种血清蛋白在 AS 组中具有显著的性别特异性变化，其中 12 种在女性中改变（APOC2、APOE、ARMC3、CLC4K、FETUB、GLCE、MRRP1、PTPA、RN149、TLE1、TRIPB、ZC3HE），一种在男性中改变（RGPD4）。AS 女性的游离雄激素指数显示出 1.63 的比值增加，与对照组相比。
总之，血清多重免疫分析和无标记 LC-MS 谱分析结果表明，成年女性 AS 患者的蛋白发生改变，主要涉及脂质转运和代谢途径，而成年男性 AS 患者则表现出炎症信号改变为主。这些结果进一步证明，在 AS 中寻找生物标志物或新型药物靶点可能需要分层为男性和女性亚组，并且可能导致新型靶向治疗方法的发展。
