Department of Global Public Health, Karolinska Institutet, Stockholm, 17177, Sweden.
Department of Neuroscience, Karolinska Institutet, Stockholm, 17177, Sweden.
Transl Psychiatry. 2022 Apr 7;12(1):148. doi: 10.1038/s41398-022-01907-z.
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 first-trimester maternal serum samples, from 318 mothers to ASD cases and 429 mothers to ASD-unaffected controls, nested within the register-based Stockholm Youth Cohort. While no overall associations between high levels of APP and ASD were observed, associations varied across diagnostic sub-groups based on co-occurring conditions. 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 = 1.92, 95% CI 1.08-3.42). Further, levels of maternal ferritin in the lowest (OR = 1.78, 95% CI 1.18-2.69) and highest (OR = 1.64, 95% CI 1.11-2.43) tertiles were associated with increased risk of any ASD diagnosis in offspring, with stronger associations still between the lowest (OR = 3.81, 95% CI 1.91-7.58) and highest (OR = 3.36, 95% CI 1.73-6.53) 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.
先前的研究支持在自闭症谱系障碍（ASD）的病因中，早期免疫紊乱的作用。与 ASD 风险相关的母体先天（非适应性）免疫状态的生物标志物研究集中在一种急性期蛋白（APP），即 C 反应蛋白（CRP）上，但结果存在争议。我们评估了来自 318 位 ASD 病例的母亲和 429 位 ASD 未受影响对照的母亲在妊娠早期血清样本中 8 种不同 APP 的水平，这些母亲都嵌套在基于登记的斯德哥尔摩青年队列中。虽然没有观察到高水平的 APP 与 ASD 之间存在总体关联，但基于并发疾病的诊断亚组，关联存在差异。与 CRP 水平处于中间三分位组相比，最低三分位组的母亲 CRP 水平与后代 ASD 无智力障碍或注意力缺陷多动障碍的风险增加相关（OR=1.92，95%CI 1.08-3.42）。此外，最低（OR=1.78，95%CI 1.18-2.69）和最高（OR=1.64，95%CI 1.11-2.43）三分位组的母体铁蛋白水平与后代任何 ASD 诊断的风险增加相关，最低和最高三分位组之间的关联仍然更强（OR=3.81，95%CI 1.91-7.58）和最高（OR=3.36，95%CI 1.73-6.53）铁蛋白三分位组与 ASD 伴智力障碍的风险。在 ASD 病例的母亲中 CRP 水平较低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。铁蛋白水平异常增加导致 ASD 表型的风险表明，在神经发育过程中铁可能具有重要作用。
