diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13316diaendo-13316Research ArticleОригинальные исследованияOriginal StudiesТранскрипционные особенности аутоиммунного сахарного диабета: дифференциальная экспрессия генов в CD4+ и CD8+ субпопуляциях Т-клеток кровиTranscriptional features of autoimmune diabetes: differentially expressed genes in CD4+ and CD8+ subpopulations of blood T cellshttps://orcid.org/0000-0003-0935-9004ГолодниковИ. И.GolodnikovI. I.

Голодников Иван Иванович, аспирант 

117036 Москва, ул. Дм. Ульянова, д. 11 

ResearcherID: AAJ-8843-2021;

Scopus Author ID: 57208628509

Ivan I. Golodnikov, PhD student

11 Dm. Ulyanova street, 117036 Moscow

ResearcherID: AAJ-8843-2021;

Scopus Author ID: 57208628509

golodnikov.ivan@endocrincentr.ruhttps://orcid.org/0009-0002-4275-847XПодшиваловаЕ. С.PodshivalovaE. S.

Подшивалова Елизавета Сергеевна

Москва

ResearcherID: ISB-5640-2023;

Scopus Author ID: 57214441739

Elizaveta S. Podshivalova

Moscow

ResearcherID: ISB-5640-2023;

Scopus Author ID: 57214441739

lia.pod@yandex.ruhttps://orcid.org/0000-0001-8489-9954ЧечехинВ. И.ChechekhinV. I.

Чечехин Вадим Игоревич, к.м.н. 

Москва

ResearcherID: AAN-6190-2020;

Scopus Author ID: 57204779390

Vadim I. Chechekhin, MD, PhD

Moscow

ResearcherID: AAN-6190-2020

vadimchex97@gmail.comhttps://orcid.org/0000-0001-5979-7411ЗубрицкийА. В.ZubritskyA. V.

Зубрицкий Анатолий Валерьевич

Москва

Scopus Author ID: 57202420882

Anatoliy A. Zubritskiy

Moscow

Scopus Author ID: 57202420882

a.zubrit@gmail.comhttps://orcid.org/0009-0005-9875-4541МатросоваА. А.MatrosovaA. A.

Матросова Алина Антоновна

Москва

Alina A. Matrosova

Moscow

matrosova.alina@endocrincentr.ruhttps://orcid.org/0000-0002-2541-3747ДворяньчиковЯ. В.DvoryanchikovY. V.

Дворяньчиков Ярослав Владимирович

Москва

Yaroslav V. Dvoryanchikov

Moscow

yaroslav.dvoryanchikov@gmail.comhttps://orcid.org/0000-0003-2852-807XСамсоноваМ. Д.SamsonovaM. D.

Самсонова Маргарита Денисовна

Москва

Margarita D. Samsonova

Moscow

samsonovamag@gmail.comhttps://orcid.org/0009-0000-9301-8848МаркеловаЕ. К.MarkelovaE. K.

Маркелова Екатерина Константиновна

Москва

Ekaterina K. Markelova

Moscow

markelova98@yandex.ruhttps://orcid.org/0000-0002-7587-1666МедведеваЮ. А.MedvedevaY. A.

Медведева Юлия Анатольевна, к.б.н. 

Москва

Yulia A. Medvedeva, PhD in Biology

Moscow

ju.medvedeva@gmail.comhttps://orcid.org/0000-0001-5656-2596НиконоваТ. В.NikonovaT. V.

Никонова Татьяна Васильевна, д.м.н. 

Москва

Tatiana V. Nikonova, MD, PhD

Moscow

tatiana_nikonova@mail.ruhttps://orcid.org/0000-0003-2122-2297БондаренкоЕ. В.BondarenkoE. V.

Бондаренко Екатерина Владимировна, к.м.н. 

Москва

Ekaterina V. Bondarenko, PhD

Moscow

ekaterinabondarenko@inbox.ruhttps://orcid.org/0000-0003-1172-3557ПоповС. В.PopovS. V.

Попов Сергей Владимирович, к.б.н. 

Москва

Sergey V. Popov, PhD in Biology

Moscow

swpopov73@gmail.comhttps://orcid.org/0000-0002-7045-8215МинниахметовИ. Р.MinniakhmetovI. R.

Минниахметов Илдар Рамилевич, к.б.н. 

Москва

Ildar R. Minniakhmetov, PhD in Biology

Moscow

minniakhmetov@gmail.comhttps://orcid.org/0000-0002-5057-127XШестаковаМ. В.ShestakovaM. V.

Шестакова Марина Владимировна, д.м.н., профессор, академик РАН 

Москва

ResearcherID: D-9123-2012;

Scopus Author ID: 7004195530

Marina V. Shestakova, MD, PhD, Professor

Moscow

ResearcherID: D-9123-2012;

Scopus Author ID: 7004195530

shestakova.mv@gmail.comГНЦ РФ ФГБУ «Национальный медицинский исследовательский центр эндокринологии»РоссияEndocrinology Research CentreRussian FederationГНЦ РФ ФГБУ «Национальный медицинский исследовательский центр эндокринологии»; Московский государственный университет имени М.В. ЛомоносоваРоссияEndocrinology Research Centre; Lomonosov Moscow State UniversityRussian FederationФедеральный исследовательский центр «Фундаментальные основы биотехнологии» Российской академии наукРоссияFederal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of SciencesRussian Federation202523052025282124135Copyright © Голодников И.И., Подшивалова Е.С., Чечехин В.И., Зубрицкий А.В., Матросова А.А., Дворяньчиков Я.В., Самсонова М.Д., Маркелова Е.К., Медведева Ю.А., Никонова Т.В., Бондаренко Е.В., Попов С.В., Минниахметов И.Р., Шестакова М.В., 20252025Голодников И.И., Подшивалова Е.С., Чечехин В.И., Зубрицкий А.В., Матросова А.А., Дворяньчиков Я.В., Самсонова М.Д., Маркелова Е.К., Медведева Ю.А., Никонова Т.В., Бондаренко Е.В., Попов С.В., Минниахметов И.Р., Шестакова М.В.Golodnikov I.I., Podshivalova E.S., Chechekhin V.I., Zubritsky A.V., Matrosova A.A., Dvoryanchikov Y.V., Samsonova M.D., Markelova E.K., Medvedeva Y.A., Nikonova T.V., Bondarenko E.V., Popov S.V., Minniakhmetov I.R., Shestakova M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/13316ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Латентный аутоиммунный диабет взрослых (LADA, latent autoimmune diabetes mellitus in adults) рассматривается как промежуточная форма между сахарным диабетом 1 типа (СД1) и 2 типа (СД2), однако молекулярные механизмы, объясняющие его уникальные клинико-патогенетические особенности, остаются недостаточно изученными. Определение дифференциально экспрессируемых генов (ДЭГ) при LADA в сравнении с СД1 необходимо для разработки более персонифицированных подходов к диагностике и терапии.

ЦЕЛЬ

ЦЕЛЬ. Определить ДЭГ в периферических мононуклеарах крови у пациентов с LADA по сравнению с СД1, а также оценить отличия этих двух групп от здоровых добровольцев.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. В исследование включены 60 человек (23 пациента с СД1 длительностью до 1 года, 15 пациентов с LADA длительностью до 5 лет и 22 здоровых добровольца). Средний возраст пациентов с LADA составил 40 [34; 45] лет, с СД1 — 26 [21; 31] лет. Дизайн — одномоментное наблюдательное одноцентровое исследование. У всех участников выделяли периферические мононуклеары крови и выполняли секвенирование РНК одиночных клеток (scRNA-seq). Дифференциальный анализ экспрессии генов проводили с использованием «псевдобалкового» подхода (pyDEseq2, p<0,05 с поправкой на множественные сравнения, |log2FoldChange|≥0,5). Статистический анализ осуществляли с применением непараметрических критериев (Краскела–Уоллиса, Манна–Уитни).

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. У пациентов с LADA выявлено снижение экспрессии HLA-G, SPARC и C20orf204 и повышение AC002460.2 по сравнению со здоровыми добровольцами (p<0,05) в CD4+ наивных Т-клетках. В группе СД1 основные отличия касались CD4+ T клеток центральной памяти (IFIT1, CASP3, LAMP3, HIST1H2BN). При сравнении LADA и СД1 статистически значимо различался только один ген (C20orf204, p<0,05) в CD4+ наивных Т-клетках.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Полученные данные свидетельствуют о близости молекулярно-генетических паттернов LADA и СД1. У пациентов с LADA наблюдаются умеренные изменения в экспрессии ряда генов, связанных с иммунной регуляцией и воспалением. Минимальные различия между этими формами СД подчеркивают сходство патогенеза.

BACKGROUND

BACKGROUND: Latent autoimmune diabetes in adults (LADA) is considered an intermediate form between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, the molecular mechanisms underlying its unique clinical and pathogenetic features remain insufficiently studied. Identifying differentially expressed genes (DEGs) in LADA compared to T1DM is essential for developing more personalized diagnostic and therapeutic approaches.

OBJECTIVE

OBJECTIVE: To identify DEGs in peripheral blood mononuclear cells (PBMCs) of patients with LADA compared to those with T1DM, and to evaluate differences in DEGs between these patient groups and healthy volunteers.

MATERIALS AND METHODS

MATERIALS AND METHODS: The study included 60 participants (23 T1DM patients with disease duration of up to 1 year, 15 LADA patients with disease duration of up to 5 years, and 22 healthy volunteers). The median age of LADA patients was 40 [34; 45] years, and for T1DM patients, 26 [21; 31] years. This was a single-center, cross-sectional observational study. PBMCs were isolated from all participants, and single-cell RNA sequencing (scRNA-seq) was performed. Differential gene expression analysis was conducted using a pseudo-bulk approach (pyDEseq2, p<0.05 adjusted for multiple comparisons, |log2FoldChange| ≥0.5). Statistical analyses employed nonparametric tests (Kruskal–Wallis, Mann–Whitney).

RESULTS

RESULTS: In LADA patients, reduced expression of HLA-G, SPARC, and C20orf204 and increased expression of AC002460.2 were observed compared to healthy volunteers (p<0.05) in CD4+ Naive T-cells. In the T1DM group, the most significant differences were identified in CD4+ Central memory T-cells (IFIT1, CASP3, LAMP3, HIST1H2BN). When comparing LADA to T1DM, only one transcript, C20orf204, showed statistically significant differential expression (p<0.05) in CD4+ Naive T-cells.

CONCLUSION

CONCLUSION: The findings indicate that LADA and T1DM share similar molecular patterns, with LADA exhibiting moderate changes in the expression of genes associated with immune regulation and inflammation. The minimal differences between these forms of diabetes highlight their pathogenetic similarity.

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