Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press140210.17650/1726-9784-2023-22-3-19-27LITERATURE REVIEW AND CLINICAL AND EXPERIMENTAL STUDYОБЗОР ЛИТЕРАТУРЫ И КЛИНИКО-ЭКСПЕРИМЕНТАЛЬНОЕ ИССЛЕДОВАНИЕMannose antibody levels in gastric cancer patients (literature review and clinical and experimental study)Уровни антител к маннозе у больных раком желудка (обзор литературы и клинико-экспериментальное исследование)https://orcid.org/0000-0002-9608-4696NikulinM. P.НикулинМ. П.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

maximpetrovich@mail.ruhttps://orcid.org/0000-0001-6003-071XShilovaN. V.ШиловаН. В.
Russian Federation

16 / 10 Miklukho-Maclay St., Moscow 117997

117997 Москва, ул. Миклухо-Маклая, 16 / 10

https://orcid.org/0000-0003-2925-9924LipatnikovA. D.ЛипатниковА. Д.
Russian Federation

16 / 10 Miklukho-Maclay St., Moscow 117997

117997 Москва, ул. Миклухо-Маклая, 16 / 10

https://orcid.org/0000-0001-8783-8874SemyanikhinaA. V.СемьянихинаА. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-5229-8203StilidiI. S.СтилидиИ. С.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-8669-4477BovinN. V.БовинН. В.
Russian Federation

16 / 10 Miklukho-Maclay St., Moscow 117997

117997 Москва, ул. Миклухо-Маклая, 16 / 10

https://orcid.org/0000-0003-3966-128XTupitsynN. N.ТупицынН. Н.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииShemyakin–Ovchinnikov Institute of bioorganic chemistry RASГНЦ «Институт биоорганической химии им. академиков М. М. Шемякина и Ю. А. Овчинникова» РАН1810202322319271710202317102023https://bioterapevt.abvpress.ru/jour/article/view/1402

Introduction. Glycans play an important role in the pathogenesis of malignant neoplasms, including stomach cancer. In recent years, the attention of many researchers has been drawn to mannose (Man) – hexose, which is an indispensable component of all N-chains of glycoproteins involved in both normal physiological and pathological processes.

Aim. To investigate the role of innate immunity factors and ways to influence them through mannose and mannose-containing glycans in gastric cancer patients.

Materials and methods. Data on the role of mannose – one of the key monosaccharides in the formation of glycoprotein N-chains – and its binding receptors (mannose receptor, mannose-binding lectin, antibodies) in gastric cancer since 2006 are presented. Levels of anti-glycan antibodies in blood serum samples of 235 gastric cancer patients and 76 healthy donors were evaluated using a glycochip.

Results. It has been shown that the level of IgM-class antibodies to Manβ – the core part of N-glycans – in gastric cancer patients is significantly lower compared to the donor group, regardless of age (p = 0.0001). To assess the effect of age on the levels of antiglycan antibodies, patients were divided into two subgroups – before and after 45 years. In the group under 45 years of age, significant differences in the levels of antiglycan antibodies to Manβ persisted, while significant differences in the levels of antiglycan antibodies to Manβ1-4GlcNAcβ were not observed. when comparing groups of patients and donors older than 45 years, the levels of antibodies to Manβ and Manβ1-4GlcNAcβ were significantly higher only in donors.

Conclusion. Deficiency of humoral immunity may be one of the key factors in the initiation and progression of carcinogenesis in humans. In our work, in patients with stomach cancer, we revealed a deficiency of antiglycan antibodies to Manβ and to Manβ1-4GlcNAcβ – core fragments of N-chains of glycoproteins, and the deficiency increased with age. The results of the study are a promising platform for further research aimed not only at studying the role of anti-mannose antibodies, but also at developing approaches to adoptive immunoprophylaxis.

Введение. Гликаны играют важную роль в патогенезе злокачественных новообразований, в том числе при раке желудка. В последние годы внимание многих исследователей привлечено к маннозе (Man) – гексозе, которая является непременным компонентом всех N-цепей гликопротеинов, участвующих как в нормальных физиологических, так и в патологических процессах.

Цель исследования – изучение роли факторов врожденного иммунитета и способов воздействия на них посредством маннозы и маннозосодержащих гликанов у больных раком желудка.

Материалы и методы. Представлены данные источников литературы с 2006 г. о роли маннозы – одного из ключевых моносахаридов при формировании N-цепей гликопротеинов – и связывающих ее рецепторов (маннозный рецептор, маннозосвязывающий лектин, антитела) при раке желудка. Исследования антигликановых антител в образцах сыворотки крови 235 больных раком желудка и 76 условно здоровых доноров выполнены с помощью гликочипа.

Результаты. Показано, что уровень антител IgM-класса к Manβ – коровой части N-гликанов – у больных раком желудка достоверно ниже по сравнению с донорской группой независимо от возраста (p = 0,0001). Для оценки влияния возраста на уровни антигликановых антител больные были разделены на 2 подгруппы – моложе и старше 45 лет. В группе моложе 45 лет достоверные различия по уровням антигликановых антител к Manβ сохранялись, в то время как достоверных различий по уровням антигликановых антител к Manβ1-4GlcNAcβ не наблюдали. При сравнении групп больных и доноров старше 45 лет уровни антител к Manβ и Manβ1-4GlcNAcβ были достоверно выше только у доноров.

Заключение. Дефицит гуморального иммунитета может быть одним из ключевых звеньев инициации или прогрессии канцерогенеза у человека. В нашей работе у больных раком желудка мы выявили дефицит антигликановых антител к Manβ и к Manβ1-4GlcNAcβ – коровым фрагментам N-цепей гликопротеинов, причем с возрастом дефицит нарастал. Представленные результаты – многообещающая платформа для дальнейших исследований, направленных не только на изучение роли антиманнозных антител, но и на разработку подходов к иммунопрофилактике.

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