초록 열기/닫기 버튼
루푸스는 면역 체계 전반의 이상 반응이 축적됨으로써 발생하는 자가 면역 질환으로, 여러 유전적 및 환경적 요인에 의해 다양한 단계에서 면역 관용이 붕괴되어 질환에 이른다. 자가 항원의 축적, 항원 제시, B 세포 및 T 세포 활성화 등 각 단계에서 이상 면역 반응이 축적되면 그 결과 자가 항체가 생성되고, 면역 복합체 형성 및 침착에 뒤따라 조직내 염증 반응이 기시됨으로써 질환이 발병한다. 루푸스 병태 생리에 관련된 다양한 면역 체계의 이상을 이해함에 따라 각 단계의 요소들이 잠재적인 치료에 이용될 수 있을 것이다.
Systemic lupus erythematosus (SLE) is a systemic inflammatory disease in which all the key components of the immune system are involved to break immune tolerance and to cause tissue inflammation. Breach of immune tolerance as evidenced by the appearance of autoantibodies is observed long before disease onset. Candidate gene analyses or genome-wide scans suggest that multiple genetic loci affecting both innate and adaptive immunity are involved in determining disease susceptibility. These genetic evidences have been further supported by abnormalities found in the cells and molecules influenced by these genes. Autoantigen accumulation by ineffective clearance of apoptotic cells due to impaired innate immune system provides persistent antigenic stimuli to expand and differentiate autoreactive T cells. Certain HLA genes further promote autoreactive T cell expansion by affecting either T cell receptor-peptide-MHC interactions or T cell repertoire selection. Defects in T cell signaling render them hyper-responsive to antigen stimuli and resistant to activation-induced cell death. B cell signaling defects help autoreactive B cells escape into periphery, lower activation threshold, and prolong survival. Pathogenic autoantibodies are produced as a result of accumulation of these abnormalities, followed by immune complex formation, complement fixation, and finally tissue damage. This review will discuss in detail the series of events involved in the break-down of immune tolerance in SLE.
키워드열기/닫기 버튼
Systemic lupus erythematosus; Pathophysiology; Autoimmunity
