mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-MDC-16744mimmun-3048Research ArticleКРАТКИЕ СООБЩЕНИЯSHORT COMMUNICATIONSЧисло копий митохондриальной ДНК в моноцитах и периферической крови у больных системной склеродермиейMitochondrial DNA copy number in monocytes and peripheral blood in patients with systemic sclerosisГерасимоваЕ. В.GerasimovaE. V.

Герасимова Елена Владимировна - к.м.н., старший научный сотрудник отдела системных ревматических заболеваний,

115522, Москва, Каширское шоссе, 34а

Elena V. Gerasimova - PhD (Medicine), Senior Research Associate, Department of Systemic Rheumatic Diseases,34a Kashirskoe Highway Moscow 115522

gerasimovaev@list.ruБогатыреваА. И.BogatyrevaA. I.

младший научный сотрудник отдела системных ревматических заболеваний;

младший научный сотрудник, младший научный сотрудник отдела системных ревматических заболеваний,

Москва

Junior Research Associate, Department of Systemic Rheumatic Diseases;

Junior Research Associate, Department of Systemic Rheumatic Diseases, 

ПопковаТ. В.PopkovaT. V.

д.м.н., начальник отдела системных ревматических заболеваний,

Москва

PhD, MD (Medicine), Head, Department of Systemic Rheumatic Diseases, 

 

ГерасимоваД. А.GerasimovaD. A.

младший научный сотрудник, ассистент кафедры организации и экономики фармации,

Москва

Junior Research Associate, Assistant, Department of Organization and Economics of Pharmacy,

 

ФГБНУ «Научно-исследовательский институт ревматологии имени В.А. Насоновой»РоссияV. Nasonova Research Institute of RheumatologyRussian FederationФГБНУ «Научно-исследовательский институт ревматологии имени В.А. Насоновой»; Научно-исследовательский институт морфологии человека имени академика А.П. Авцына ФГБНУ «Российский научный центр хирургии имени академика Б.В. Петровского»РоссияV. Nasonova Research Institute of Rheumatology; A. Avtsyn Research Institute of Human Morphology, V. Petrovsky Russian National Research Center of SurgeryRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова»РоссияI. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation202426072024264771776Copyright © Герасимова Е.В., Богатырева А.И., Попкова Т.В., Герасимова Д.А., 20242024Герасимова Е.В., Богатырева А.И., Попкова Т.В., Герасимова Д.А.Gerasimova E.V., Bogatyreva A.I., Popkova T.V., Gerasimova D.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/3048

Клетки врожденного иммунитета являются важными участниками воспалительных и фиброзных процессов при системной склеродермии (ССД). В патогенезе ССД задействованы иммунные клетки, в первую очередь макрофаги, в основе нарушений которых лежит митохондриальная дисфункция клеток. В качестве суррогатного маркера митохондриальной дисфункции клеток используется число копий митохондриальной ДНК (мтДНК).

Цель исследования – оценить количество копий мтДНК в CD14+ моноцитах и во всех популяциях клеток, циркулирующих в крови, у больных ССД по сравнению со здоровым контролем.

В исследование были включены 25 пациентов с ССД (22 женщины и 3 мужчин, медиана возраста 49 (43-57) лет и длительности заболевания 4,6 (1,0-9,6) лет) и 25 человек без аутоиммунных или хронических воспалительных заболеваний, сопоставимых по возрасту и полу. Большинство пациентов (80%) имели ограниченную форму ССД. Больные ССД не получали противоревматическую терапию. ДНК выделяли из CD14+ моноцитов и цельной крови. Абсолютное число копий мтДНК измеряли с помощью цифровой ПЦР. Величину числа копий мтДНК на клетку, использованную для анализа, рассчитывали как соотношение копий мтДНК и яДНК.

Установлено, что у больных ССД количество копий мтДНК в CD14+ моноцитах было выше (108 (60-162) против 72 (59-79), р = 0,01), а показатель всех популяций клеток, циркулирующих в крови, не различался по сравнению с контрольной группой (109 (72-171) и 128 (85-227), p = 0,17). Выявилена негативная связь количества копий мтДНК с длительностью заболевания и позитивная – c ЛПС-стимулированной секрецией IL-6 культивируемыми CD14+ моноцитами.

Результаты исследования позволяют предположить, что увеличение числа копий мтДНК в CD14+ моноцитах является возможным механизмом поддержания сниженной функции дефектных митохондрий в моноцитах пациентов с ССД, связанной с развитием и прогрессированием ССД.

Innate immune cells are important participants in inflammatory and fibrotic processes in systemic scleroderma (SSc). The pathogenesis of SSc involves immune cells, primarily macrophages, whose disorders are based on mitochondrial cell dysfunction. Mitochondrial DNA (mtDNA) copy number is used as a surrogate marker of mitochondrial cell dysfunction. The aim of the study was to evaluate the number of mtDNA copies in CD14+ monocytes and in all cell populations circulating in the blood in patients with SSc compared to healthy controls.

The study included 25 patients with SSc (22 women and 3 men, median age 49 (43-57) years and disease duration 4.6 (1.0-9.6) years) and 25 people without autoimmune diseases or chronic inflammatory diseases matched by age and gender. The majority of patients (80%) had a limited form of SSc. All study participants did not receive antirheumatic therapy. DNA was isolated from CD14+ monocytes and whole blood. Absolute mtDNA copy number was measured using digital PCR. The number of mtDNA copies per cell used for analysis was calculated as the ratio of mtDNA and nDNA copies.

It was found that in patients with SSc, the number of mtDNA copies in CD14+ monocytes was higher (108 (60-162) vs 72 (59-79), p = 0.01), and the indicator of all cell populations circulating in the blood did not differ in compared with the control group (109 (72-171) and 128 (85-227), p = 0.17). A negative relationship was found between the number of mtDNA copies and the duration of the disease, and a positive relationship with LPS-stimulated IL-6 secretion by cultured CD14+ monocytes.

The study results suggest that increase of mtDNA copy number in CD14+ monocytes is a possible mechanism to maintain the reduced function of defective mitochondria in monocytes from patients with SSc associated with the development and progression of SSc.

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