Аутоантитела при системной склеродермии: спектр, клинические ассоциации и прогностическое значение

Цель обзора – клиническая оценка циркулирующих аутоантител при системной склеродермии (ССД). Подробно рассмотрены «болезнь-специфические», т. е. ассоциированные с заболеванием, антиядерные аутоантитела: к центромерам, к топоизомеразе 1; группа антинуклеолярных антител – к рибонуклеопротеазе III (АРНКП-III), Th/T0, Pm/Scl, а также аутоантитела к рибонуклеопротеинам UIRP и U3RNP. Частота выявления антиядерных аутоантител высока (90–95%), при этом каждое из аутоантител в отдельности обнаруживается у небольшого числа больных с определенными клинической картиной, характером течения, прогнозом и имеет четкие генетические ассоциации. Показана четкая ассоциация между типом аутоантител, характером органных осложнений и выживаемостью. Специфичные аутоантитела относятся к предикторам течения болезни и ее исхода. Насколько клинические различия между подгруппами отражают патогенетические различия иммунной дисрегуляции, остается неясным. Специфичные для ССД аутоантитела появляются на самом раннем этапе заболевания, до того как клиническая картина болезни станет развернутой. Подробно описаны их диагностическая значимость и место в новых классификационных критериях заболевания 2013 г. Обоснована важность внедрения в клиническую практику определения антицентромерных, антитопоизомеразных аутоантител и антител к РНК-протеиназе III. Определение антител к РНК-протеиназе III имеет большое значение в связи с важностью выделения особого подтипа ССД, потенциально имеющего плохой прогноз, в том числе в связи с повышенной частотой развития онкологических заболеваний. Представляется целесообразным при формулировке диагноза больного ССД указывать его позитивность по основным «склеродермическим» аутоантителам.

Последний раздел обзора посвящен неспецифическим аутоантителам, направленным на такие мишени, как эндотелиальные клетки и фибробласты, функциональные молекулы (различные клеточные рецепторы), белки экстрацеллюлярного матрикса, энзимы и др. Затронут ряд интересных гипотез и теорий, объясняющих инициирующую роль этой подгруппы аутоантител в возникновении и развитии ССД.

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