Современные подходы к лабораторной диагностике ревматических заболеваний: роль молекулярных и клеточных биомаркеров

Достижения лабораторной медицины начала XXI в., обусловленные разработкой и быстрым внедрением в практику инновационных молекулярно-клеточных технологий, способствовали увеличению диагностической чувствительности и специфичности лабораторных тестов и существенному расширению спектра исследуемых биомаркеров в ревматологии. В последнее десятилетие для определения биомаркеров ревматических заболеваний (РЗ) в крови, синовиальной жидкости, моче, биоптатах синовиальной оболочки, почек и других пораженных тканей применяют высокотехнологичные автоматизированные аналитические системы с использованием как «классических» униплексных методов иммунохимического анализа (непрямая реакция иммунофлюоресценции, иммуноферментный анализ, иммуноблот, иммунодот, иммунонефелометрия, хемилюминесцентный иммунный анализ, радиоиммуноанализ), так и мультиплексных диагностических платформ на основе ДНК-, РНК-, белковых и клеточных микрочипов, полимеразной цепной реакции, проточной цитометрии, масс-спектрометрии.

Современная генерация молекулярных и клеточных биомаркеров (аутоантитела, острофазовые белки воспаления, цитокины, хемокины, маркеры активации сосудистого эндотелия, иммуноглобулины, компоненты системы комплемента, субпопуляции лимфоцитов, продукты метаболизма костной и хрящевой ткани, внутриклеточные сигнальные молекулы, протеазы, генетические, эпигенетические, транскриптомные маркеры) является важным инструментом для профилактики, ранней диагностики, оценки активности, скорости прогрессирования, клинико-лабораторных субтипов РЗ, прогнозирования эффективности терапии и риска развития нежелательных реакций на фоне лечения.

Расшифровка ключевых патогенетических механизмов РЗ позволила идентифицировать молекулярные и клеточные биомаркеры, которые могут быть использованы в качестве терапевтических «мишеней». В настоящее время для лечения РЗ успешно применяются генно-инженерные биологические препараты (моноклональные антитела и гибридные белковые молекулы), селективно ингибирующие провоспалительные цитокины и мембранные молекулы, опосредующие патологическую активацию иммунокомпетентных клеток. К альтернативным методам терапии РЗ относится использование низкомолекулярных химически синтезированных препаратов, подавляющих активность тирозинкиназ. Важным направлением терапии РЗ является восстановление иммунологической толерантности и коррекция аутоиммунных нарушений с помощью аутологичных гемопоэтических стволовых клеток, мезенхимальных стромальных клеток, аутологичных толерогенных дендритных клеток, Т- и В-регуляторных клеток, генной терапии, пептидных антигенов. Перспективы лабораторной диагностики РЗ связаны с необходимостью гармонизации и стандартизации современных методов определения аутоантител, поиском и клинической валидацией новых протеомных, транскриптомных и геномных биомаркеров.

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