Otizm Spektrum Bozukluğu’nda bir İmmün Fenotip: Kan-Beyin ve Bağırsak Bariyeri Proteinlerine Karşı Otoimmünite ve Otistik Belirtilerle İlişkisi

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by restricted interests, repetitive behaviors and disturbances in social communication. Despite its high prevalence, its etiopathogenesis is not fully understood. Genetic changes, gastrointestinal abnormalities and conditions associated with immune system responses are thought to play a role in the pathophysiology of ASD. In our study, it was mainly aimed to investigate the clinical phenotypes related to autoimmune factors in ASD. For this purpose, 41 children with ASD between the ages of 4-10 and 24 age- and sex-matched healthy children were included in the study. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, DSM-5-Turkish Adaptation (K-SADS-PL-DSM-5-T), Childhood Autism Rating Scale (CARS), Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Criteria (QPGS-RIII) and Bristol Stool Scale were applied by the clinician to all participants. Parents were asked to fill in the Aberrant Behavior Checklist (ABC), Autism Behavior Checklist (AuBC), Conners Parent Rating Scale-Revised Short Turkish Form (CPRS-RS) and Social Responsiveness Scale (SRS). Anti-claudin-5 and anti-β-catenin IgG autoantibody concentrations were measured in serum samples. In addition, standardized ELISA index values were calculated for both autoantibodies in order to analyze all samples. Anti-claudin-5 and anti-β-catenin IgG autoantibody concentration and ELISA index values were compared in ASD and control groups. The relationship between autoantibody ELISA index values and scale scores in the ASD group was analyzed. In addition, autoantibody concentrations, ELISA index values and scale scores were compared in the ASD group with at least one GIS symptom (GIS+) and those without GIS symptoms (GIS-). In order to evaluate the variables in clinically more homogeneous subgroups, the ASD group; stereotypical behavior and insistence on sameness (SB/IS), sensory hypo/hypersensitivity (SH/H), social relationship/communication skills (SR/C), ADHD symptoms are divided into subgroups with high and low levels of symptoms. Autoantibody concentrations and ELISA index levels were compared in these subgroups. Finally, the ASD group was divided into subgroups with high and low autoantibody ELISA indices, and scale scores were compared between the two groups. As a result of the study, gas complaints (GC), GIS+ rate, anti-claudin-5 IgG autoantibody concentration and ELISA index levels were found to be significantly higher in the ASD group compared to the control group. Although it approached statistical significance between the groups in terms of anti-β-catenin IgG autoantibody concentration and ELISA index, no difference was detected. It was observed that those with GIS+ in the ASD group had lower ASD severity compared to the GIS- group. It was determined that there was a negative correlation with anti-β-catenin IgG ELISA index and ABC lethargy; AuBC body-object use, language skills, social-self-care; SRS social cognition subscale and the SRS total score. In the ASD group, no difference was observed between the GIS+ and GIS- groups in terms of autoantibody concentration and ELISA index levels. Anti-β-catenin IgG ELISA index was significantly lower in the subgroup with high SB/IS formed by cluster analysis in the ASD group. In the subgroup with high anti-β-catenin IgG autoantibody ELISA index; AuBC body-object use and language skills subscale scores were found to be significantly low. There was no significant difference between the anti-claudin-5 IgG ELISA index subgroups in terms of scale scores. Our study is the first to our knowledge examining anti-claudin-5 and anti-β-catenin IgG autoantibodies in ASD. As a result, anti-claudin-5 IgG autoantibody concentration and ELISA index were found to be higher than the control group, regardless of the disease phenotype in patients with ASD. The difference between the two groups for anti-β-catenin IgG autoantibody concentration and ELISA index approached the level of significance. Anti-β-catenin IgG ELISA index was significantly lower in the ASD subgroup with high SH-TI. Also, ODKL body object use and language skills subscale scores were low in the group with high anti-β-catenin IgG ELISA index. This suggests that there may be an ASD subgroup with an autoimmunity associated milder clinical phenotype. Further studies with larger samples are needed on the subject.