Analysis of new biomarker for evaluation of SLE activity with autoantibody penetration to cells

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590483
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Tohoku University
• Principal Investigator: ISHII Tomonori Tohoku University, HOSPITAL, Research Associate (10282138)
• Co-Investigator(Kenkyū-buntansha): HARIGAE Hideo TOHOKU UNIVERSITY, HOSPITAL, Lecturer (50302146)
• Project Period (FY): 2005 – 2006
• Keywords: SLE / anti-DNA antibody / Dendritic cell / MLR

Research Abstract

Systemic lupus erythematosus (SLE) involves a variety of autoantibodies which may be responsible for the tissue injury. Immunoglobulin G (IgG), especially anti-DNA IgG from active SLE had an ability to penetrate into peripheral blood mononuclear cells in vitro. The target cells for the penetration are CD8 (+) T cells, B cells, NK cells, monocytes, dendritic cells (DC) in circulation. Anti-Fc antibodies failed to cause the inhibition of anti-DNA IgG penetration into cells, but the coexistence of methyl beta cyclodextrin, raft/caveolae inhibitor, or DNA antigen blocked the internalization. Immunofluorescence studies revealed that anti-DNA IgG used raft/caveolae for their entry into the cells, and were distributed in lysosome, but not detected in the nuclei. The penetration caused to alter the biological function of the immunocytes. Namely, purified anti-DNA IgG induced the maturation and activation of human monocyte-derived dendritic cell as observed by CD83 up-regulation, IL12 secretion and an enhanced stimulation of allogenic or autologus T cells to DC at mixed lymphocyte reaction. Our results provide a new sight for the role of anti-DNA autoantibodies at cell function such as maturation and production of several proteins like cytokines, and may explain a novel mechanism where peripheral tolerance is broken in SLE patients.