Increased Serum Concentrations of High Mobility Group Box 1 (HMGB1) Protein in Children with Autism Spectrum Disorder.

Gerasimos Makris,George P Chrousos,Charalabos Papageorgiou,Filia Apostolakou,Panagiota Pervanidou,Giorgos Chouliaras,Ioannis Papassotiriou

doi:10.3390/children8060478

Abstract

High mobility group box 1 protein (HMGB1) has been suggested to be involved in the immune dysfunction and inflammation reported in autism spectrum disorder (ASD). We aimed to assess HMGB1 serum concentrations (SCs) in high-functioning ASD children compared to typically developing (TD) controls and to explore their associations with the autism spectrum quotient (AQ), the empathy quotient (EQ), and the systemizing quotient (SQ). The study involved 42 ASD children and 38 TD children, all-male, aged between 6.1 and 13.3 years old. HMGB1 SCs were measured by enzyme-linked immunosorbent assay (ELISA). Groups were comparable regarding age, general IQ, birth weight, and maternal age at birth. ASD children showed significantly higher HMGB1 SCs compared to TD children (1.25 ± 0.84 ng/mL versus 1.13 ± 0.79 ng/mL, respectively, p = 0.039). The Spearman’s rho revealed that HMGB1 SCs were positively correlated with the AQ attention to detail subscale (rs = 0.46, p = 0.045) and with the SQ total score (rs = 0.42, p = 0.04) in the ASD group. These results show that HMGB1 serum concentrations are altered in ASD children, and suggest that inflammatory processes mediated by HMGB1 may be associated with specific cognitive features observed in ASD.

Highlights

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which occurs in early childhood and is characterized by impairments in social communication and by restricted, repetitive, and stereotyped patterns of behavior [1]
We explore for the first time the relations of High mobility group box 1 protein (HMGB1) serum levels to the autism spectrum quotient, and to the empathizing and systemizing abilities that have been considered accountable for social deficits and non-social phenotypic characteristics of ASD
Children in the ASD group had significantly lower verbal intelligence quotient (IQ) compared to typically developing (TD) children

Summary

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which occurs in early childhood and is characterized by impairments in social communication and by restricted, repetitive, and stereotyped patterns of behavior [1]. Altered immune responses have been reported in ASD ranging from alterations of immune markers in the periphery to increased microglia activation in the central nervous system (CNS), all of them leading to a chronic state of low-grade inflammation in the CNS [4,5,6]. Several studies have shown peripheral immune abnormalities in patients with ASD, including abnormal or skewed T helper cell cytokine profiles [3], an imbalance of serum immunoglobulin levels [7], NK cell activation [8], increased monocyte responses [9], and increased levels of complement components [10]. IL-33, HMGB1, heat-shock protein (HSP), and S100 protein could be suitable as biomarkers of inflammation in ASD [4]

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