McLellan Janna, Croen Lisa A, Iosif Ana-Maria, Ashwood Paul, Yoshida Cathleen, Berger Kimberly, Van de Water Judy
Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California Davis, 451 Health Sciences Drive, Suite 6505C, Davis, CA 95616, United States.
Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612, United States.
Cereb Cortex. 2024 May 2;34(13):50-62. doi: 10.1093/cercor/bhae082.
Associations between maternal immune dysregulation (including autoimmunity and skewed cytokine/chemokine profiles) and offspring neurodevelopmental disorders such as autism have been reported. In maternal autoantibody-related autism, specific maternally derived autoantibodies can access the fetal compartment to target eight proteins critical for neurodevelopment. We examined the relationship between maternal autoantibodies to the eight maternal autoantibody-related autism proteins and cytokine/chemokine profiles in the second trimester of pregnancy in mothers of children later diagnosed with autism and their neonates' cytokine/chemokine profiles. Using banked maternal serum samples from 15 to 19 weeks of gestation from the Early Markers for Autism Study and corresponding banked newborn bloodspots, we identified three maternal/offspring groups based on maternal autoantibody status: (1) mothers with autoantibodies to one or more of the eight maternal autoantibody-related autismassociated proteins but not a maternal autoantibody-related autism-specific pattern, (2) mothers with a known maternal autoantibody-related autism pattern, and (3) mothers without autoantibodies to any of the eight maternal autoantibody-related autism proteins. Using a multiplex platform, we measured maternal second trimester and neonatal cytokine/chemokine levels. This combined analysis aimed to determine potential associations between maternal autoantibodies and the maternal and neonatal cytokine/chemokine profiles, each of which has been shown to have implications on offspring neurodevelopment independently.
已有报道称，母体免疫失调（包括自身免疫以及细胞因子/趋化因子谱异常）与后代神经发育障碍（如自闭症）之间存在关联。在与母体自身抗体相关的自闭症中，特定的母体来源自身抗体可进入胎儿体内，作用于对神经发育至关重要的8种蛋白质。我们研究了后来被诊断为自闭症儿童的母亲在妊娠中期针对8种与母体自身抗体相关的自闭症蛋白质的自身抗体与细胞因子/趋化因子谱之间的关系，以及她们新生儿的细胞因子/趋化因子谱。利用自闭症早期标志物研究中妊娠15至19周的母体血清样本库以及相应的新生儿血斑样本库，我们根据母体自身抗体状态确定了三个母体/后代组：（1）对8种与母体自身抗体相关的自闭症相关蛋白质中的一种或多种有自身抗体，但无母体自身抗体相关自闭症特异性模式的母亲；（2）有已知母体自身抗体相关自闭症模式的母亲；（3）对8种与母体自身抗体相关的自闭症蛋白质均无自身抗体的母亲。我们使用多重检测平台测量了母体妊娠中期和新生儿的细胞因子/趋化因子水平。这项综合分析旨在确定母体自身抗体与母体和新生儿细胞因子/趋化因子谱之间的潜在关联，其中每一项均已被证明独立地对后代神经发育有影响。
