Korean J Med.  2010 Apr;78(4):403-408.

Update on the pathophysiology of systemic lupus erythematosus

• Kang EH

Abstract

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.

Keyword

Systemic lupus erythematosus; Pathophysiology; Autoimmunity

MeSH Terms

Adaptive Immunity
Antigen-Antibody Complex
Autoantibodies
Autoimmunity
B-Lymphocytes
Cell Death
Complement System Proteins
Disease Susceptibility
Genetic Association Studies
Genetic Loci
Immune System
Immune Tolerance
Inflammation
Lupus Erythematosus, Systemic
T-Lymphocytes
United Nations
Antigen-Antibody Complex
Autoantibodies
Complement System Proteins