Autoimmunity is triggered by cPR-3 (105-201), a protein complementary to human autoantigen proteinase-3

Speaker: 徐毅玲         Commentator: 葉才明 老師

Date: 2/25/2004; 13:00-14:00 (Room 601)

Abstract:

    It remains unclear how and why autoimmunity occurs. Pathogenic

autoantibodies against the body’s self proteins are associated with inflammatory autoimmune diseases. Antineutrophil cytoplasmic antibodies (ANCA) which recognize myeloperoxidase (MPO) and proteinase-3 (PR-3) are such examples. In vitro, the pathogenicity begins when ANCA binds to the MPO or PR-3 on the surface of neutrophils. Neutrophils are then activated and release inflammatory mediators. e.g. ROS, which in turn lead to vasculitis. The authors found that some PR-3 ANCA patients not only have antibodies to PR-3, but also antibodies to the peptides produced by the antisense strand of the PR-3. They also confirmed that antibody to cPR-3 is distinct, rather than being a single cross-reactive polyclonal antibody. Furthermore, antibodies to PR-3 and cPR-3 can bind to each other. This indicate that the two antibodies are an idiotypic pair. The author recapitulate the human idiotypic response in mice by immunizing mice with human recombinant cPR-3. They found that mice produce antibodies to cPR-3 and PR-3 as well. So, cPR-3 may be an initiator of the autoimmune disease. When searching for microbial or fungal mimics of cPR-3, they found several candidates such as S. aureus and E histolytica. The authors implicate antisense transcripts as potential pathological agents for the first time. Their results suggest that antibody transfer or gene therapy to induce or prevent anti-idiotype antibody formation may important than immunosuppressive therapy.

References:

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(1998)