medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2025-8-26-32medalphabet-4353Research ArticleСтатьиОценка распространенности HLA-DRB1 и DQB1 гаплотипов и их взаимосвязи с тяжелым и рефрактерным течением акантолитической пузырчатки в Российской популяцииAnalysis of HLA DRB1-DQB1 haplotypes prevalence and their association with severe and refractory pemphigus in Russian populationhttps://orcid.org/0000-0002-4365-3090ЛепеховаА.  А.LepekhovaA.  A.

Лепехова Анфиса Александровна, к.м.н., доцент

Москва

Lepekhova Anfisa A., PhD Med, associate professor

Moscow

anfisa.lepehova@yandex.ruhttps://orcid.org/0000-0003-2482-1754ОлисоваО. Ю.OlisovaO. Yu.

Олисова Ольга Юрьевна, д.м.н., профессор

Москва

Olisova Olga Yu., DM Sci (habil.), professor

Moscow

olisovaolga@mail.ruhttps://orcid.org/0000-0003-2433-7727ДуханинА. С.DukhaninA. S.

Духанин Александр Сергеевич, д.м.н., профессор

Москва

Dukhanin Alexander S., DM Sci (habil.), professor

Moscow

das03@rambler.ruhttps://orcid.org/0000-0002-5800-4800ТеплюкН. П.TeplyukN. P.

Теплюк Наталия Павловна, д.м.н., профессор

Москва

Teplyuk Natalia P., DM Sci (habil.), professor

Moscow

teplyukn@gmail.comhttps://orcid.org/0000-0001-8887-4420ШимановскийН. Л.ShimanovskyN. L.

Шимановский Николай Львович, д.м.н., профессор; член-корр. РАН

Москва

Shimanovskiy Nikolay L., DM Sci (habil.) professor; Corresponding Member of the Russian Academy of Sciences

Moscow

shiman@rsmu.ruФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский университет)РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Минздрава РоссииРоссияN.I. Pirogov Russian National Research Medical UniversityRussian Federation20250406202508Дерматология (1)2632Copyright © Лепехова А.А., Олисова О.Ю., Духанин А.С., Теплюк Н.П., Шимановский Н.Л., 20252025Лепехова А.А., Олисова О.Ю., Духанин А.С., Теплюк Н.П., Шимановский Н.Л.Lepekhova A. ., Olisova O.Y., Dukhanin A.S., Teplyuk N.P., Shimanovsky N.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/4353Исправление

Исправление: В названии статьи вместо «HLA DRB1-DR Q1 гаплотипов» следует читать «HLA-DRB1 и DQB1 гаплотипов»Обоснование. Акантолитическая пузырчатка представляет собой тяжелое, жизне-угрожающее аутоиммунное, генетически детерминированное заболевание, характеризующееся формированием аутоантител класса IgG к мембранам клеток шиповатого слоя и возникновением интраэпидермальных пузырей на коже и слизистых оболочках. Известно, что HLA аллели I и II классов являются потенциальными факторами риска развития заболевания. Ассоциация пузырчатки с HLA аллелями была подтверждена секвенированием и генотипированием в различных этических группах. Чаще всего в мировой популяции в развитие АП вносят весомый вклад DRB1*04:02, DRB1*14:01, DRB1*14:04 и DQB1*05:04 HLA аллели. Существенную роль в развитии АП играют также гаплотипы, которые представляют собой сочетания аллелей (вариантов генов). Следует отметить, что распространенность DRB 1/DQB 1 гаплотипов у больных пузырчаткой, а также их возможная взаимосвязь с тяжелым и рефрактерным течением заболевания в российской популяции не исследовалась.

Цель исследования

Цель исследования. Оценить распространенность HLA-DRB1/HLA-DQB1 гаплотипов в низком разрешении у пациентов с АП и их взаимосвязь с устойчивостью к терапии системными глюкокортикостероидами и степенью тяжести заболевания.

Материалы и методы

Материалы и методы. В исследовании принимали участие 106 больных АП. Из них 70 женщин и 36 мужчин. В группу контроля входило 92 здоровых добровольца. Из них 52 женщины и 40 мужчин. Степень тяжести заболевания оценивалась с помощью индекса PDAI. Наличие стероидной резистентности анализировалось с помощью консенсуса Murrell 2008 года. HLA типирование проводилось с помощью полимеразной цепной реакции. Для сравнения частот гаплотипов между группами здоровых доноров и пациентов с АП использовался точный тест Фишера.

Результаты

Результаты. Гаплотипы DRB 1*04/DQB 1*05 и DRB 1*14/DQB 1*03 предрасполагали к развитию АП в российской популяции (p<0,00067; p><0,008643). Кроме того, у пациентов с данными гаплотипами наблюдалась тенденция к более тяжелому течению заболевания. Однако, статистически значимых различий по данным признакам получено не было. Следует отметить, что гаплотип DRB1*11/DQB1*03 наблюдался только у здоровых доноров, что говорит о его протективной роли в отношении развития АП в российской популяции. Заключение. В проводимом исследовании были получены генетические биомаркеры предрасположенности к развитию АП в российской популяции. В перспективе данные гаплотипы можно рассмотреть в качестве предикторов среднего и тяжелого течения заболевания.><0,00067; p<0,008643) . Кроме того, у пациентов с данными гаплотипами наблюдалась тенденция к более тяжелому течению заболевания. Однако, статистически значимых различий по данным признакам получено не было. Следует отметить, что гаплотип DRB1*11/DQB1*03 наблюдался только у здоровых доноров, что говорит о его протективной роли в отношении развития АП в российской популяции.

Заключение

Заключение. В проводимом исследовании были получены генетические биомаркеры предрасположенности к развитию АП в российской популяции. В перспективе данные гаплотипы можно рассмотреть в качестве предикторов среднего и тяжелого течения заболевания.

Introduction

Introduction. Pemphigus is known to be a life-threatening genetically predisposed autoimmune condition characterized by the formation of IgG antibodies to desmogleins 1 and 3 (Dsg 1, 3) in stratum spinosum and granulosum resulting in blister formation. HLA I and II class antigens express on a vast variety of immune cells including dendritic cells, macrophages, monocytes, Langerhans cells, endothelial cells, and thymic epithelial cells and, therefore play a crucial role in disease’ pathogenesis. The association of pemphigus with HLA alleles has been confirmed through sequencing and genotype analysis across various ethnic groups. In global population the disease development is significantly influenced by specific genetic factors, particularly the HLA alleles DRB1*04:02, DRB1*14:01, DRB1*14:04, and DQB1*05:04. A significant role in the development of pemphigus is attributed to haplotypes, which are combinations of alleles (gene variants). Notably, that the prevalence of DRB 1/DQB 1 haplotypes among patients with pemphigus, as well as their potential association with the disease severity and steroid-resistance in Russian population, has yet to be investigated.

The aim of study

The aim of study. To evaluate the prevalence of HLA-DRB1-HLA-DQB1 haplotypes at low-resolution level in pemphigus patients and their potential association with the disease severity and reluctance to systemic steroid therapy.

Materials and methods

Materials and methods. A total of 106 patients with confirmed diagnosis of pemphigus were genotyped for HLA class II genotypes. HLA frequencies were compared with unrelated healthy blood donors (n=92). Disease severity was assessed by PDAI index. The presence of steroid resistance was analyzed using the Murrell consensus from 2008. HLA typing was performed via PCR reaction. The statistical significance of differences between patients and controls was evaluated using Fisher’s exact test.

Results

Results. We found that DRB1*04/DQB1*05 and DRB1*14/DQB1*03 haplotypes predisposed to disease progression in Russian population (p<0,00067; p<0,008643). Moreover, patients who carried these haplotypes showed a tendency towards moderate and severe disease course. However, no statistically significant differences were found for these characteristics. It is also important to highlight that DRB1*11/DQB1*03 haplotype was found exclusively in healthy volunteers indicating its protective role against pemphigus in Russian population.

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