Neonatal immune signatures differ by sex regardless of neurodevelopmental disorder status: Macrophage migration inhibitory factor (MIF) alone reveals a sex by diagnosis interaction effect

Kim, Danielle H. J.; Iosif, Ana‐Maria; Ramirez-Celis, Alexandra; Ashwood, Paul; Ames, Jennifer; Lyall, Kristen; Berger, Kimberly; Croen, Lisa; Water, Judy Van de

doi:10.1016/j.bbi.2023.05.002

Cited by 6 publications

(3 citation statements)

References 28 publications

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“…Sex-specific effects on both IL-8 and MIF levels have been previously reported. 35 – 39 Our observation that sex-specific IL-8 and MIF levels in trauma patients exhibit an opposite trend from what is observed in healthy controls indicates that a disruption of the immune system due to traumatic injury can also lead to a disruption of sex-specific immune responses. This should be taken into account for the development of therapeutics that incorporate knowledge of sex-specific immune responses.…”

Section: Discussionmentioning

confidence: 79%

Development of a predictive algorithm for patient survival after traumatic injury using a five analyte blood panel

Fathi,

Karkanitsa,

Rupert

et al. 2024

Preprint

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Severe trauma can induce systemic inflammation but also immunosuppression, which makes understanding the immune response of trauma patients critical for therapeutic development and treatment approaches. By evaluating plasma of 50 healthy volunteers and 1000 trauma patients across five trauma centers in the United States, we identified 6 novel changes in immune proteins after traumatic injury and further new variations by sex, age, trauma type, comorbidities, as well as a new biomarker predictor of patient survival. Blood was collected at the time of arrival at Level 1 trauma centers and patients were stratified based on trauma level, tissues injured, and injury types. Trauma patients had significantly upregulated proteins associated with immune activation (IL-23, MIP-5), immunosuppression (IL-10) and pleiotropic cytokines (IL-29, IL-6). A high ratio of IL-29 to IL-10 was identified as a new predictor of survival with ROC area of 0.933. Using machine learning, we identified three increased proteins (MIF, TRAIL, IL-29) and three decreased proteins (IL-7, TPO, IL-8) that were the most important in distinguishing a trauma blood profile from those of healthy controls. Biologic sex altered phenotype with IL-8 and MIF being lower in healthy women, but higher in female trauma patients when compared to male counterparts. This work identifies new responses to injury that may influence systemic immune dysfunction, serving as targets for therapeutics and immediate clinical benefit in identifying at-risk patients.

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Section: Discussionmentioning

confidence: 79%

Development of a predictive algorithm for patient survival after traumatic injury using a five analyte blood panel

Fathi,

Karkanitsa,

Rupert

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Photobiomodulatory treatment (PBMT) exerts beneficial neuromodulatory effects by activating the JAK2/STAT4/STAT5 signaling pathway to promote IFN-γ/IL-10 expression in non-substantial CD4 T cells and induces improved brain microenvironmental conditions and alleviates cognitive deficits in a mouse model ( 137 ). Moreover, neonatal immune profiles vary by sex, and their cytokine and chemokine concentrations are sex-differentiated and associated with neurodevelopmental outcomes ( 138 ).…”

Section: Neuroinflammation and Immunitymentioning

confidence: 99%

Neuroplasticity of children in autism spectrum disorder

Chen,

Wang,

Zhang

et al. 2024

Front. Psychiatry

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder that encompasses a range of symptoms including difficulties in verbal communication, social interaction, limited interests, and repetitive behaviors. Neuroplasticity refers to the structural and functional changes that occur in the nervous system to adapt and respond to changes in the external environment. In simpler terms, it is the brain’s ability to learn and adapt to new environments. However, individuals with ASD exhibit abnormal neuroplasticity, which impacts information processing, sensory processing, and social cognition, leading to the manifestation of corresponding symptoms. This paper aims to review the current research progress on ASD neuroplasticity, focusing on genetics, environment, neural pathways, neuroinflammation, and immunity. The findings will provide a theoretical foundation and insights for intervention and treatment in pediatric fields related to ASD.

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“…Individuals with ASD also had elevated levels of pro-inflammatory cytokines in the amniotic fluid [ 1 ]. Neonatal blood spot data also shows dysregulated cytokine levels in children later diagnosed with ASD [ 36 , 38 ]. Maternal immune activation (MIA) models, whether induced via infectious agents or maternal conditions, have been associated with ASD-like behaviors in adult offspring and altered levels of cytokines in the brain [ 23 , 54 , 57 , 65 , 66 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of maternal immune activation and sex on placental and fetal brain cytokine and gene expression profiles in a preclinical model of neurodevelopmental disorders

Osman,

Moreno,

Rose

et al. 2024

J Neuroinflammation

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Maternal inflammation during gestation is associated with a later diagnosis of neurodevelopmental disorders including autism spectrum disorder (ASD). However, the specific impact of maternal immune activation (MIA) on placental and fetal brain development remains insufficiently understood. This study aimed to investigate the effects of MIA by analyzing placental and brain tissues obtained from the offspring of pregnant C57BL/6 dams exposed to polyinosinic: polycytidylic acid (poly I: C) on embryonic day 12.5. Cytokine and mRNA content in the placenta and brain tissues were assessed using multiplex cytokine assays and bulk-RNA sequencing on embryonic day 17.5. In the placenta, male MIA offspring exhibited higher levels of GM-CSF, IL-6, TNFα, and LT-α, but there were no differences in female MIA offspring. Furthermore, differentially expressed genes (DEG) in the placental tissues of MIA offspring were found to be enriched in processes related to synaptic vesicles and neuronal development. Placental mRNA from male and female MIA offspring were both enriched in synaptic and neuronal development terms, whereas females were also enriched for terms related to excitatory and inhibitory signaling. In the fetal brain of MIA offspring, increased levels of IL-28B and IL-25 were observed with male MIA offspring and increased levels of LT-α were observed in the female offspring. Notably, we identified few stable MIA fetal brain DEG, with no male specific difference whereas females had DEG related to immune cytokine signaling. Overall, these findings support the hypothesis that MIA contributes to the sex- specific abnormalities observed in ASD, possibly through altered neuron developed from exposure to inflammatory cytokines. Future research should aim to investigate how interactions between the placenta and fetal brain contribute to altered neuronal development in the context of MIA.

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Neonatal immune signatures differ by sex regardless of neurodevelopmental disorder status: Macrophage migration inhibitory factor (MIF) alone reveals a sex by diagnosis interaction effect

Cited by 6 publications

References 28 publications

Development of a predictive algorithm for patient survival after traumatic injury using a five analyte blood panel

Development of a predictive algorithm for patient survival after traumatic injury using a five analyte blood panel

Neuroplasticity of children in autism spectrum disorder

Impact of maternal immune activation and sex on placental and fetal brain cytokine and gene expression profiles in a preclinical model of neurodevelopmental disorders

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