mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-CIP-2588mimmun-2588Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESКлиникоиммунологические фенотипы течения расстройств аутистического спектраClinical-immunological phenotypes of the autistic spectrum disordershttps://orcid.org/0000-0002-6320-5017ЧеревкоН. А.CherevkoN. A.

Черевко Н.А. – д.м.н., профессор кафедры иммунологиии аллергологии

634055,  г. Томск, Московский тракт, 2.Тел.: 8 (913) 920-50-52

Cherevko N.A., PhD, MD (Medicine), Professor, Departmentof Immunology and Allergology

2 Moskovskiy tract Tomsk 634055 Phone: +7 (913) 920-50-52

chna@0370.ruhttps://orcid.org/0000-0002-6320-5017ХудяковаМ. И.KhudiakovaM. I.

Худякова М.И. – соискатель кафедры патофизиологии

Томск

Khudiakova M.I., External PhD Student

Tomsk

khudiakovami@mail.ruhttps://orcid.org/0000-0001-6673-7556КлимовВ. В.KlimovV. V.

Климов В.В. – д.м.н., профессор, заведующий кафедройиммунологии и аллергологии

Томск

Klimov V.V., PhD, MD (Medicine), Professor, Head, Department of Immunology and Allergology

Tomsk

klimov@mail.tomsknet.ruНовиковП. С.NovikovP. S.

Новиков П.С. – соискатель кафедры патофизиологии

Томск

Novikov P.S., PhD Applicant, Department of Pathophysiology

Tomsk

pavel.N1234@yandex.ruНикитинаА. А.NikitinaA. A.

Никитина А.А. – семейный врач, заведующая дневнымстационаром

Томск

Nikitina A.A., Family Doctor, Head of the Day Hospital

Tomsk

anastasiaannikitina@gmail.comБерезовскаяК. В.BerezovskayaK. V.

Березовская К.В. – врач общей врачебной практики,врач-педиатр

Томск

Berezovskaya K.V., General Practitioner, Pediatrician

Tomsk

info@0370.ruКошкароваН. С.KoshkarovaN. S.

Кошкарова Н.С. – к.м.н., доцент кафедры иммунологиии аллергологии

Томск

Koshkarova N.S., PhD (Medicine), Associate Professor,Department of Immunology and Allergology

Tomsk

kasy@list.ruДенисовА. А.DenisovA. A.

Денисов А.А. – д.м.н., профессор кафедры иммунологиии аллергологии

Томск

Denisov A.A., PhD, MD (Medicine), Professor, Departmentof Allergology and Immunology

Tomsk

mh@0370.ruФГБОУ ВО «Сибирский государственный медицинский университет» Министерства здравоохранения РФРоссияSiberian State Medical UniversityRussian FederationФГБОУ ВО «Сибирский государственный медицинский университет» Министерства здравоохранения РФ; ООО «Центр семейной медицины»Russian FederationSiberian State Medical University; Center for Family Medicine LLCRussian FederationООО «Центр семейной медицины»РоссияCenter for Family Medicine LLCRussian FederationООО «Центр Семейной Медицины»РоссияCenter for Family Medicine LLCRussian Federation202314112022252319330Copyright © Черевко Н.А., Худякова М.И., Климов В.В., Новиков П.С., Никитина А.А., Березовская К.В., Кошкарова Н.С., Денисов А.А., 20232023Черевко Н.А., Худякова М.И., Климов В.В., Новиков П.С., Никитина А.А., Березовская К.В., Кошкарова Н.С., Денисов А.А.Cherevko N.A., Khudiakova M.I., Klimov V.V., Novikov P.S., Nikitina A.A., Berezovskaya K.V., Koshkarova N.S., Denisov A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2588

РАС страдает каждый 59-й ребенок. У пациентов с РАС чаще, чем в популяции в целом, присутствуют сопутствующие расстройства, которые могут усугубить течение основного заболевания или повлиять на постановку диагноза.

Цель работы – выделить клинико-иммунологические фенотипы течения РАС.

Материалом исследования служили образцы крови детей двух групп исследования: дети с РАС (n = 100) и клинически здоровые (n = 30). На основании наличия сопутствующих заболеваний дети были разделены на 3 фенотипа: судорожный, инфекционный, дермато-респираторный и желудочнокишечный.

В сыворотке крови определяли концентрации цитокинов IL-4, IL-6, IL-10, IFNγ, IL-17А. Модифицированным методом ИФА с применением методологии Immunohealth™ определяли концентрацию spIgG к 111 пищевым антигенам (пАГ). Оценку показателей когнитивных и психофизиологических показателей у детей проводили с помощью анкеты АТЕС.

В результате исследования выделены клинико-иммунологические фенотипы течения РАС, связанные с особым типом пищевой реактивности, цитокиновым профилем, клинической тяжестью психо-физиологических расстройств и сопутствующими коморбидными заболеваниями.

Во всех четырех фенотипах установлена повышенная активность синтеза специфических антител, связанного с изученным пАГ гуморального иммунитета, повышенная концентрация суммарного spIgG к пАГ и концентрации spIgG к бобовым продуктам и казеину, значения С-реактивного белка.

При этом в судорожном фенотипе (сопутствующие эпилепсия и судороги) максимальные концентрации spIgG установлены к пасленовым продуктам, повышена концентрация IL-10 и снижена концентрация IL-4, снижено содержание сывороточного железа и ферритина.

В инфекционном фенотипе (часто болеющие дети) – к зерновым и бродильным продуктам, повышены концентрации IL-10 и IFNγ и снижена концентрация IL-4, повышены абсолютное и относительное количество лимфоцитов и фибриноген.

В дермато-респираторном фенотипе (кожные высыпания) – к молочным продуктам, повышены концентрации IL-4 и IL-17А.

В желудочно-кишечном фенотипе зарегистрировано самое высокое количество реакций повышенных IgG к наибольшему спектру пАГ на фоне тенденции изменения в цитокиновом профиле в сторону повышения IFNγ в соотношениях IFNγ/IL-4 и IFNγ/IL-10.

Таким образом, выделенные фенотипы течения РАС связаны с влиянием пАГ и отражают особый вариант иммунологического воспалительного патогенеза, что позволяет персонифицировать элиминационные диеты, предложить мероприятия по коррекции и индивидуальной профилактике и, вероятно, рассчитать прогноз течения заболевания.

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.

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The authors declare that there are no conflicts of interest present.