АТИПИЧНЫЙ ГЕМОЛИТИКО-УРЕМИЧЕСКИЙ СИНДРОМ

Гемолитико-уремический синдром (ГУС) характеризуется триадой, представленной механической гемолитической анемией, тромбоцитопенией и почечной недостаточностью. Атипичным ГУС (аГУС) считается ГУС, не связанный с действием Шига-токсина, и хотя ряд авторов выделяют вторичный аГУС, обусловленный S. pneumoniae или другими причинами, аГУС представляет собой первичное заболевание, обусловленное нарушением регуляции альтернативного пути активации комплемента. Среди случаев ГУС у детей только 5–10% можно отнести к атипичным, тогда как у взрослых атипичными являются подавляющее число случаев ГУС. Частота встречаемости комплемент-зависимого аГУС на сегодняшний день точно неизвестна. Тем не менее, сообщается более чем о 1000 пациентах с аГУС, обследованных на наличие нарушений системы комплемента. Развитие заболевания возможно от неонатального периода и до взрослого возраста. У большинства пациентов аГУС манифестирует гемолитической анемией, тромбоцитопенией и почечной недостаточностью, и у 20% отмечаются внепочечные проявления. От 2 до 10% больных умирают, у одной трети пациентов развивается терминальная почечная недостаточность при первой атаке. У половины пациентов отмечаются рецидивы заболевания. Обнаружено наличие мутаций генов, кодирующих регуляторные белки системы комплемента, фактора Н, мембранного кофакторного белка (MCP), фактора I и тромбомодулина, у 20–30, 5–15, 4–10 и 3–5% соответственно и мутации генов кодирующих белки С3-конвертазы, С3 и фактора В – у 2–10% и 1–4%. Кроме того, у 6–10% пациентов выявляются антитела к фактору Н. Критериями постановки диагноза аГУС являются: 1) отсутствие ассоциированного заболевания; 2) отсутствие критериев ГУС, связанного с Шига-токсином (посев кала и ПЦР на Шига-токсины; серология на антилипополисахаридные антитела); 3) отсутствие критериев тромботической тромбоцитопенической пурпуры (активность ADAMTS13 сыворотки больше 10%). Необходимо исследование системы комплемента (С3,С4, концентрации в плазме фактора Н и фактора I, экспрессии на лейкоцитах MCP и антител к фактору Н; генетический скрининг факторов риска). При анализе родословных, по крайней мере, у 20% заболевание имело наследственный характер с аутосомно-рецессивным или доминатным путем наследования. В связи с тем, что пенетрантность заболевания составляет 50%, генетическое консультирование крайне затруднено. До настоящего времени терапией первой линии является плазмотерапия, при отсутствии бесспорных доказательств её эффективности. При трансплантации, за исключением случаев MCP-ГУС, существует высокий риск посттрансплантационных рецидивов. Описанные клинические случаи и два исследования второй фазы демонстрируют впечатляющую эффективность блокатора C5 компонента комплимента экулизумаба, предполагая, что он будет являться следующим стандартом терапии. За исключением пациентов, получающих интенсивную плазмотерапию или терапию экулизумабом, наихудший прогноз отмечается у пациентов с H-фактором – ГУС, при котором смертность может достигать 20%, а у 50% выживших пациентов функция почек не восстанавливается. Терминальная почечная недостаточность развивается у половины больных с I-фактором ГУС. У большинства пациентов с MCP-ГУС функция почек, напротив, остается сохранной. У пациентов с ГУС, обусловленным действием антител к фактору Н (анти-Н-ГУС) при раннем начале терапии отмечается благоприятный исход.

Вклад авторов. CL и VFB обсудили содержание статьи, написали оригинал, редактировали его и утвердили окончательный вариант. VFB выполнил исследование системы комплемента и генетический скрининг.

Конфликт интересов. С. Loirat была координатором французского исследования «Безопасность и эффективность экулизумаба у взрослых пациентов с аГУС, резистентных/чувствительных к плазмотерапии «C08-002A и C08-003A», является координатором французских исследований «Применение экулизумаба у взрослых и детей с аГУС «С10-004 и С10-003», а также является членом научноконсультативного совета при Alexion Pharmaceutical sand LFB Biotechnologies. В. Frémeaux-Bacchi является членом научно-консультативного совета при Alexion Pharmaceuticals.

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