全身性エリテマトーデスの原因遺伝子の解明とそれに基づく新規治療法の可能性

Autoimmune diseases are caused by defective genes, aberrant gene expression or regulation, and environmental factors. Autoimmune disease susceptibility is determined by the interplay of these factors, which eventually affect autoreactive lymphocyte activation status or cell death sensitivity. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a broad variety of clinical symptoms and autoantibody production against nucleic acids, typically double-stranded DNA. Several lines of evidence indicate SLE development has a strong genetic basis. Recent studies have shown that most of the peripheral CD4+ or CD8+ T-cells have a potential to respond to self-antigens and persistence of such self antigens in vivo can provoke human or murine SLE. These recent findings in basic and clinical immunology would cause us to reconsider the importance of antigen clearance and persistence as a cause of SLE. Thus, I would like to review the lymphocyte abnormal responses seen in SLE patients from the view point of defective self-antigen clearance.