Анализ экспрессии генов в крови как дополнительный инструмент мониторинга терапии метотрексатом больных ревматоидным артритом

Цель – оценить изменения клинических, иммунологических, рентгенологических показателей и экспрессии генов mTOR (mammalian target of rapamycin), главного регулятора клеточного роста и пролиферации; ULK1 (маркер аутофагии); р21 (ингибитор циклинзависимых киназ); каспазы 3 (индикатор апоптозной активности); ММП9 (матриксная металлопротеиназа 9) и катепсина К, участвующих в деструкции сустава, а также провоспалительного цитокина ФНОα (фактор некроза опухоли α) в крови больных ревматоидным артритом (РА) при терапии метотрексатом (МТ).
Материал и методы. Обследовано 33 больных РА (21– позитивный и 12 – негативных по ревматоидному фактору – РФ; средний возраст 47,1 года) и 28 здоровых доноров (средний возраст 45,1 года). Все больные получали МТ в течение 2 лет. Клинический ответ оценивали по индексу DAS28, определяли также СОЭ, сывороточный уровень антител к циклическому цитруллинированному пептиду (АЦЦП), С-реактивного белка (СРБ) и РФ. Деструктивные изменения суставов оценивали с помощью рентгенографии. Экспрессию генов определяли в клетках периферической крови посредством обратно-транскриптазной реакции и полимеразной цепной реакции в режиме реального времени.
Результаты. Терапия МТ значительно снижала активность заболевания по индексу DAS28, скованность, число припухших и болезненных суставов как у серопозитивных (РФ+), так и у серонегативных (РФ-) больных РА. При этом
10 больных достигли состояния ремиссии к концу исследования. У РФ- больных РА отсутствие прогрессирования разрушения суставов сопровождалось отсутствием значительных изменений экспрессии ММП9 и катепсина К, а также более сильным подавлением ФНОα, экспрессия которого становилась сравнимой с контрольными лицами. У больных, достигших ремиссии, наблюдалось значительное снижение уровня экспрессии гена катепсина К по сравнению с началом исследования. У РФ+ больных РА терапия МТ приводила к статистически достоверному снижению клинических и иммунологических показателей, однако наблюдалось увеличение числа эрозий и дальнейшее сужение суставных щелей. Это сопровождалось значительным повышением экспрессии генов ММП9, катепсина К и ФНОα по сравнению со здоровыми лицами.
Заключение. Изменение экспрессии генов, ответственных за разрушение матрикса гиалинового хряща и кости, – ММП9 и катепсина К, а также уровень ФНОα в крови больных РА при терапии МТ коррелируют с изменениями клинических, иммунологических и рентгенологических параметров, используемых для оценки состояния больного в клинической практике.

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