The Alteration of Salivary Immunoglobulin A in Autism Spectrum Disorders.

Wuyi Gong,Xiaohui Mi,Yanan Qiao,Xiaoguo Zheng,Mingbang Wang,Ruihuan Xu,Yongming Li,Bosheng Li

doi:10.3389/fpsyt.2021.669193

Abstract

Objectives: Autism spectrum disorders (ASD) are neurodevelopmental disorders with changes in the gut and oral microbiota. Based on the intimate relationship between the oral microbiota and oral mucosal immunity, this study aimed to investigate changes in salivary immunoglobulin A (IgA) level in ASD and the underlying mechanism for any such changes.Methods: We recruited 36 children diagnosed with ASD and 35 normally developing children and measured their salivary IgA content using enzyme-linked immunosorbent assay (ELISA). The valproate (VPA) -treated ASD mouse model was established by prenatal exposure to valproate and mouse salivary IgA content was also quantified by ELISA. The submandibular glands of VPA and control mice were isolated and analyzed using qRT-PCR, immunofluorescence staining, and flow cytometry. ASD-related Streptococci were co-incubated with the human salivary gland (HSG) cell line, and western blotting was used to detect the levels of relevant proteins.Results: We found that salivary IgA content was significantly decreased in patients with ASD and had a significant ASD diagnostic value. The salivary IgA content also decreased in VPA mice and was significantly correlated with autistic-like behaviors among them. The mRNA and protein levels of the polymeric immunoglobulin receptor (Pigr) were downregulated in the submandibular glands of VPA mice and the Pigr mRNA level was positively correlated with mouse salivary IgA content. HSG cells treated with ASD-related Streptococci had reduced PIGR protein level.Conclusion: Therefore, protective IgA levels were reduced in the saliva of individuals with ASD, which correlated with the bacteria-induced downregulation of Pigr in salivary glands. This study suggests a new direction for ASD diagnosis and prevention of oral diseases in ASD cohorts and provides evidence for the ASD mucosal immunophenotype in the oral cavity.

Highlights

Autism spectrum disorders (ASD) are early-onset neurodevelopmental disorders characterized by core deficits in language and social interaction, anxiety, and stereotypic behaviors [1]
To examine the salivary immunoglobulin A (IgA) level in ASD and typically developing (TD) groups, saliva samples were tested by enzyme-linked immunosorbent assay (ELISA)
We subsequently evaluated the diagnostic performance of salivary IgA and found that the area under the receiver operator characteristic (ROC) curve (AUC) reached 71.5% (p = 0.002), indicating that the salivary IgA level was effective for ASD diagnosis

Summary

Introduction

Autism spectrum disorders (ASD) are early-onset neurodevelopmental disorders characterized by core deficits in language and social interaction, anxiety, and stereotypic behaviors [1]. ASD affect one in 59 children in the United States of America [2], and the prevalence rate in Chinese children has reached 0.70% [3]. Compared to normally developed children, the abundance of Haemophilus and Streptococci has been reported to be significantly higher in children with ASD, whereas the abundance of Prevotella, Selenomonas, Actinomyces, Porphyromonas, and Fusobacterium has been found to be reduced [9]. This altered composition of the oral microbiota is believed to affect oral mucosal immunity, since a delicate balance is maintained by oral mucosal immunity tolerating commensal bacteria while expelling pathogenic antigens. Salivary immunoglobulin A (IgA) plays an important role [10, 11]

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Conclusion