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Những hiểu biết từ các bệnh nhiễm sắc thể gây ra bởi interferon: So sánh CANDLE, SAVI với AGS, Lupus đơn gen
Tóm tắt
Các rối loạn viêm tự phát là các tình trạng viêm vô khuẩn đặc trưng bởi các đợt sốt khởi phát sớm và các mẫu viêm cơ quan đặc trưng cho bệnh. Gần đây, những phát hiện về các rối loạn đơn gen có dấu hiệu interferon loại I (IFN) mạnh do các đột biến trong quá trình phân hủy proteasome và các con đường cảm nhận RNA và DNA tế bào chất đã gợi ý về vai trò gây bệnh của IFN trong việc gây ra các kiểu hình viêm tự phát. Chữ ký gen phản ứng IFN (IGS) đã được liên kết với lupus ban đỏ hệ thống (SLE) và các bệnh tự miễn khác. Trong bài tổng quan này, chúng tôi so sánh các biểu hiện lâm sàng và sinh bệnh học của hai bệnh viêm tự phát được trung gian bởi IFN là CANDLE và SAVI với hội chứng Aicardi Goutières (AGS) và các dạng đơn gen của SLE (monoSLE) do các đột biến mất chức năng trong bổ thể 1 (C1q) hoặc các nucleases DNA, DNASE1 và DNASE1L3. Chúng tôi phác thảo sự khác biệt trong các con đường tín hiệu tế bào nội bào thúc đẩy một chu trình khuếch đại IFN loại I có tính chất bệnh lý. Trong khi sự khuếch đại IFN chủ yếu là do sự thiếu hụt chức năng của các tế bào miễn dịch bẩm sinh trong SAVI, CANDLE và AGS, các kháng thể tự miễn chống lại kháng nguyên RNA và DNA đã biến đổi tương tác với các mô và các tế bào miễn dịch bao gồm cả bạch cầu trung tính và góp phần vào việc điều chỉnh IFN ở một số bệnh nhân SLE bao gồm monoSLE, qua đó biện minh cho việc nhóm các bệnh “viêm tự phát” và “interferonopathies tự miễn” lại với nhau. Việc hiểu biết sự khác biệt trong các nguồn tế bào và các con đường tín hiệu sẽ hướng dẫn phát triển thuốc mới và sử dụng các liệu pháp mục tiêu đang nổi lên.
Từ khóa
#rối loạn viêm tự phát #interferon loại I #lupus ban đỏ hệ thống #CANDLE #SAVI #hội chứng Aicardi GoutièresTài liệu tham khảo
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