Clinical-immunological phenotypes of the autistic spectrum disorders

Abstract

Autistic spectrum disorders (ASD) affect about one in every 59 children. It is noteworthy that patients with ASD are more likely to have other comorbidities than the general population. Undoubtedly, they may aggravate clinical course of the underlying disease or affect the diagnostics. The aim of this work was to identify clinical and immunological phenotypes of the ASD clinical course. Patients and methods. The study included children classified in 2 groups: pediatric patients with ASD (n = 100), and clinically healthy children (n = 30). Based on the presence of comorbidities, the children were divided into 3 types of clinical patterns: convulsive, infectious, dermato-respiratory and gastrointestinal phenotypes. Cytokine concentrations in blood serum were determined by ELISA using Bender Medsystems (Austria) for IL-17А and Vector-Best (Russia) for IL-4, IL-6, IL-10, IFNγ. The concentration of spIgG to 111 nutritional antigens (IgG) was determined by a modified ELISA method using the Immunohealth™ technique. Assessment of cognitive and psychophysiological indices in children was carried out using the ATEC questionnaire. As a result of the study, clinical and immunological phenotypes were identified among the ASD patients, being associated with certain types of food tolerance, cytokine profile, clinical severity of psycho-physiological disorders and concomitant comorbid diseases. In all four phenotypes, were have revealed an increased synthesis of specific antibodies associated with humoral immunity for the studied food antigens, increased concentration of total spIgG to food antigens, concentration of spIgG to legumes and casein, and C-reactive protein levels.Moreover, in convulsive phenotype (concomitant epilepsy and convulsions), the maximal concentrations of spIgG are shown for Solanaceae products, the concentration of IL-10 is increased, IL-4 amounts are reduced, and the content of serum iron and ferritin is also lowered. In the infectious phenotype (frequently ill children) the spIg’s to grain and fermented products are detected, IL-10 and IFNγ concentrations are increased and IL-4 contents is reduced, along with increased absolute and relative number of lymphocytes and fibrinogen. In the dermato-respiratory phenotype (skin rashes) – to dairy products, the concentrations of IL-4 and IL-17A are increased. In the gastrointestinal phenotype, the highest number of elevated IgG responses to the largest range of food antigens was found in presence of changing cytokine profile , i.e., an increase in IFNγ in IFNγ/IL-4 and IFNγ/IL-10 ratios. Thus, the identified phenotypes of the ASD course are associated with the influence of food antigens and reflect a special variant of the immunological inflammatory pathogenesis, which makes it possible to personalize elimination diets, propose measures for correction and individual prevention, and, probably, to predict clinical course of the disease.

Keywords

• autistic spectrum disorders
• phenotypes
• dermato-respiratory
• gastrointestinal