Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral abnormalities such as impairments in social function and deficits in communication. The etiology of autism is unknown in most cases, but many studies have pointed towards the immune system as a causative agent in autism. Specific studies implicated lymphocytes, natural killer (NK) cells, monocytes, cytokines, and specific transcription factors in the development of ASD. The protein Ki-67 is n expressed in the proliferating cells and is used as a tool in several disorders. Ki-67 plays a crucial role in many neurological diseases. However, Ki-67 role in ASD is not fully understood. In this study, we investigated the possible role of Ki-67 expression in autistic children. We compared Ki-67 production in CD3+, CD4+, CD8+, CXCR4+, CXCR7+, CD45R+, HLA-DR+, GATA3+, Helios+, and FOXP3+ peripheral blood mononuclear cells (PBMCs) in autistic children to typically developing (TD) controls using immunofluorescence staining. We also determined Ki-67 mRNA levels in PBMCs using RT–PCR. The results revealed that autistic children had significantly increased numbers of CD3+Ki-67+, CD4+Ki-67+, CD8+Ki-67+, CXCR4+Ki-67+, CXCR7+Ki-67+, CD45R+Ki-67+, HLA-DR+Ki-67+, CXCR4+GATA3+, GATA3+Ki-67+ cells and decreased Helios+Ki-67+ and FOXP3+Ki-67+ cells compared with TD controls. In addition, the autistic children showed upregulation of Ki-67 mRNA levels compared with TD controls. Further studies need to be carried out to assess the exact role of Ki-67 and its therapeutic potential in ASD.

Highlights

  • Autism spectrum disorder (ASD) is a group of complex multifactorial neurodevelopmental and behaviorally defined conditions [1] characterized by deficits in social communications and the presence of restricted, repetitive behavioral patterns, interests, or activities [2]

  • We previously reported that immune dysfunction is caused by an imbalance in inflammatory mediators and transcription factor signaling in autistic children [10,11]

  • The number of Ki-67-producing CD3+ cells in children with ASD and typically developing (TD) controls in peripheral blood mononuclear cells (PBMCs) was evaluated with flow cytometry

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Summary

Introduction

Autism spectrum disorder (ASD) is a group of complex multifactorial neurodevelopmental and behaviorally defined conditions [1] characterized by deficits in social communications and the presence of restricted, repetitive behavioral patterns, interests, or activities [2]. Increased chemokine receptor activation plays an essential role in immune dysfunction in autistic children, and chemokine receptor expression is upregulated in the peripheral and brain tissue of autistic individuals [12,13]. Activation of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway may play an essential role in immune dysfunction in autistic individuals [15]. Previous studies indicate that changes in Human Leukocyte Antigen – DR isotype (HLA-DR), a marker of T-cell activation, are associated with ASD [19,20]. Increasing levels of GATA3 in PC-12 cells triggered ASD development [27]. We hypothesized that Ki-67 expression could be dysregulated in immune cells of children with ASD. Informed written consent for participation in the study was signed by the parents or the legal guardians of the subjects

Study Participants
Study Measurements
Chemicals and Antibodies
Flow Cytometric Analysis
Gene Expression
Statistics
Results
Conclusions
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