Previous research supports a contribution of early-life immune disturbances in the etiology of autism spectrum disorders (ASD). Biomarker studies of the maternal innate (non-adaptive) immune status related to ASD risk have focused on one of the acute phase proteins (APP), C-reactive protein (CRP), with conflicting results. We evaluated levels of eight different APP in maternal serum samples drawn in first trimester, from 318 mothers to ASD-cases and 429 mothers to ASD-unaffected controls, nested within the register-based Stockholm Youth Cohort. Overall, we found no general trend of high levels of maternal APP being associated with increased risk of ASD. In contrast, maternal levels of CRP in the lowest compared to the middle tertile were associated with increased risk of ASD without ID or ADHD in offspring (OR = 2.15, 95 % CI 1.17-3.93). Further, levels of maternal ferritin in the lowest (OR = 1.82, 95 % CI 1.19-2.78) and highest (OR = 1.74, 95 % CI 1.16-2.60) tertiles were associated with increased risk of any ASD diagnosis in offspring, with stronger associations still between the lowest (OR = 3.58, 95 % CI 1.79-7.17) and highest (OR = 3.20, 95 % CI 1.62-6.29) tertiles of ferritin and risk of ASD with ID. The biological interpretation of lower CRP-levels among mothers to ASD-cases is not clear but might be related to the function of the maternal innate immune system. The finding of aberrant levels of ferritin conferring risk of ASD-phenotypes indicates a plausibly important role of iron during neurodevelopment.

中文翻译：

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孕早期孕妇的急性期蛋白水平和后代自闭症谱系障碍的风险

先前的研究支持自闭症谱系障碍（ASD）病因的早期生命免疫紊乱的贡献。与ASD风险相关的母亲先天性（非适应性）免疫状态的生物标志物研究集中在急性期蛋白（APP），C反应蛋白（CRP）之一，结果却相矛盾。我们评估了妊娠早期三个月在孕妇血清样本中提取的八种不同APP的水平，它们分别来自318名母亲至ASD病例，以及429名母亲至未受ASD影响的对照，嵌套在基于登记册的斯德哥尔摩青年队列中。总体而言，我们没有发现高水平的母亲APP与ASD风险增加相关的一般趋势。相比之下，与中三分位数相比最低的母亲CRP水平与后代中没有ID或ADHD的ASD风险增加有关（OR = 2.15，95％CI 1.17-3.93）。进一步，最低（OR = 1.82，95％CI 1.19-2.78）和最高（OR = 1.74，95％CI 1.16-2.60）三元组中母亲铁蛋白水平与后代进行任何ASD诊断的风险增加相关，但仍存在更强的关联性铁蛋白最低（OR = 3.58，95％CI 1.79-7.17）和最高（OR = 3.20，95％CI 1.62-6.29）之间以及ID为ASD的风险之间。对ASD病例母亲中较低的CRP水平的生物学解释尚不清楚，但可能与母体先天免疫系统的功能有关。铁蛋白异常水平的发现带来了ASD表型的风险，这表明铁在神经发育过程中起着重要的作用。60）三分位数与后代中任何ASD诊断的风险增加相关，最低三分位数（OR = 3.58，95％CI 1.79-7.17）与最高三分位数（OR = 3.20，95％CI 1.62-6.29）铁蛋白和具有ID的ASD风险。对ASD病例母亲中较低的CRP水平的生物学解释尚不清楚，但可能与母体先天免疫系统的功能有关。铁蛋白异常水平的发现带来了ASD表型的风险，这表明铁在神经发育过程中起着重要的作用。60）三分位数与后代中任何ASD诊断的风险增加相关，最低三分位数（OR = 3.58，95％CI 1.79-7.17）和最高（OR = 3.20，95％CI 1.62-6.29）之间仍然存在更强的关联铁蛋白和具有ID的ASD风险。对ASD病例母亲中较低的CRP水平的生物学解释尚不清楚，但可能与母体先天免疫系统的功能有关。铁蛋白异常水平的发现带来了ASD表型的风险，这表明铁在神经发育过程中起着重要的作用。对ASD病例母亲中较低的CRP水平的生物学解释尚不清楚，但可能与母体先天免疫系统的功能有关。铁蛋白异常水平的发现带来了ASD表型的风险，这表明铁在神经发育过程中起着重要的作用。对ASD病例母亲中较低的CRP水平的生物学解释尚不清楚，但可能与母体先天免疫系统的功能有关。铁蛋白异常水平的发现带来了ASD表型的风险，这表明铁在神经发育过程中起着重要的作用。