Abstract
Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of “pro-inflammatory” cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented.Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1β - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.
Highlights
Still’s disease in children and adult Still’s disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity
The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of “pro-inflammatory” cytokines – interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators
A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented
Summary
Иммунопатологические процессы, лежащие в основе БСВ, являются предметом интенсивных исследований [18]. Особое значение может иметь образования NETs, продукты которых участвуют в активации NLRP3 инфламмасомы, CD68+CD86+ макрофагов и стимулируют синтез ИЛ-1β, ИЛ-6 и ФНО-α [27,28,29]. Определенное место в иммунопатогенезе БСВ играет дефицит цитотоксической активности ЕК-клеток, ассоциирующийся с гиперпродукцией ИФН-γ, гиперэкспрессией рецепторов ИЛ-12 и ИЛ-15, что приводит к нарушению контроля активации макрофагов и лимфоцитов [32, 33]. Обсуждается нарушение механизмов разрешения (resolution) воспаления, однако их значение при БСВ (как и при других ИВЗ) изучено недостаточно [36]. У пациентов с БСВ весьма характерно обнаружение маркеров цитомегаловирусной (ЦМВ) инфекции: увеличение титров антител к ЦМФ, ДНК-ЦМФ вирусной нагрузки и экспрессии «сенсоров» нуклеиновых кислот IFI6 (interferon inducible gene 6), AIM2 (Absent In Melanoma 2), участвующих в развитии воспаления [43]. В других исследованиях было показано, что при БСВ неструктурный белок парвовируса В18, активируя NLRP3 инфламмасому, индуцирует экспрессию ИЛ-1β и ИЛ-18 [44]
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