Деплеционно-реституционная терапия аутоиммунных ревматических заболеваний. Часть 1. Фундаментальные предпосылки и эффективность современных технологий лечения: анти-В-клеточные препараты и CAR-T-терапия

Ключевым звеном патогенеза системных аутоиммунных ревматических заболеваний являются нарушение иммунологической толерантности и формирование пула аутореактивных клеток. Последствиями этого становятся неконтролируемая активация эффекторного звена клеточного (Т-лимфоциты) и гуморального (В-лимфоциты и плазматические клетки) звеньев иммунитета, пролиферация аутореактивных клонов, формирование и персистенция клеток иммунологической памяти. При этом Т-, В- и плазматические клетки иммунологической памяти во взаимодействии с комплексом патогенных сигналов микроокружения обеспечивают стабильность и адаптивность формирующегося воспалительного процесса.

В современной клинической практике при назначении лекарственных препаратов превалирует подход «терапевтической пирамиды» с постепенной эскалацией воздействия до достижения ремиссии. Он не затрагивает механизмы иммунологической толерантности, в связи с чем проводится пожизненно и ассоциирован с множеством нежелательных явлений.

Предлагается использование термина «деплеционно-реституционная терапия» – ДРТ [depletion (англ.) – опустошение, истощение; restitutio ad integrum (лат.) – восстановление до первоначального, полное восстановление] для альтернативного подхода, который характеризует методы, основанные на массивном кратковременном цитотоксическом воздействии, приводящем к глубокой редукции патогенных аутореактивных клеточных клонов с последующей репопуляцией за счет «наивных» клеточных элементов и, соответственно, восстановлению механизмов толерантности и формированию сверхдлительной безлекарственной ремиссии. В настоящее время принципы ДРТ уже интегрированы в онкогематологии и неврологии. Наиболее перспективными потенциальными мишенями такой терапии в ревматологии считаются эффекторы гуморального звена иммунитета: В-клетки, плазмобласты и плазматические клетки. К наиболее перспективным средствам реализации данного подхода можно отнести CAR-T-клетки и терапевтические биспецифические моноклональные антитела.

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