Immunological and Immunogenetic Changes in Children with Autistic Disorder in Republic of Macedonia

Mirko Spiroski

doi:10.3889/seejim.2015.20003

Abstract

AIM: The aim of the study was to present our results about immunological and immunogenetic investigations in children with autistic disorder in Republic of Macedonia.METHODS: Infantile autism was diagnosed by DSM-IV and ICD-10 criteria. Plasma samples were collected from 35 autistic subjects, and their 21 siblings (biological brothers and sisters) who served as healthy controls. Plasma samples were separated by centrifugation and stored at –20°C until the determination. Plasma immunoglobulin classes (IgM, IgA, IgG) and subclasses (IgG1, IgG2, IgG3, IgG4) were determined using a nephelometer Analyzer. Specific IgA and IgG antibodies against some food allergens, as well as total IgE have been determined with automated immunofluorescent device with solid phase - UniCAP 100 (AmershamBiosciences). HLA DNA typing of class I genes was performed using a Reverse Line Strip method (RLS), and the Sequencing Based Typing method (SBT) was used for typing of class II genes.RESULTS: Children with autism had significantly higher plasma concentrations of IgG4 (p<0.001) compared to their siblings (healthy brothers or sisters). IgE specific antibodies, as well as plasma concentration of total IgE were statistically significant higher in plasma of participants with autism. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0.001), and healthy brothers and sisters from the fathers and mothers (p < 0.001). Our results showed significantly increased frequencies of HLA-C*03 (OR = 2.74*; c2= 4.68; p = 0.03), and HLA-DRB1*01 (OR = 3.10*; c2= 6.26; p = 0.012) alleles in autistic patients when compared to the controls.CONCLUSION: Children with autism have increased plasma concentration of immunoglobulines. Our results demonstrate an association of HLA-C*03 and HLA-DRB1*01 alleles with Macedonian autistic patients. Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

Highlights

Autism is a severe neurodevelopmental disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviors, and interests [1].immune system plays an important role in the pathogenesis of autism
Our results showed significantly increased frequencies of human leukocyte antigen (HLA)-C*03 (OR = 2.74*; 2= 4.68; p = 0.03), and HLA-DRB1*01 (OR = 3.10*; 2= 6.26; p = 0.012) alleles in autistic patients when compared to the controls
Our results demonstrate an association of HLA-C*03 and HLA-DRB1*01 alleles with Macedonian autistic patients

Summary

Introduction

Immune system plays an important role in the pathogenesis of autism. These include changes in lymphocyte subsets [5], alteration in serum concentration of immunoglobulin classes and subclasses [6, 7] and cytokine production [8], presence of autoantibodies to neural antigens [9], increased frequency of the C4b null allele [10], and linkage to some immune response genes [11]. A number of factors have been implicated in the pathogenesis of autism including genetic [2], environmental [3], and immunological factors [4]. The immune abnormalities would appear to be causative [16]

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