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Cartilage has been found to act as a molecular sponge that can absorb blood-borne molecules, which are then targeted by pathogenic antibodies. Two reports in the April issue of Nature Immunology show that joint cartilage is a passive surface that absorbs proteins from the bloodstream. Cartilage lacks the normal cellular controls to prevent antibody-triggered immune attacks. Its unique surface properties help to explain the tissue-specificity of arthritic disease.
In a mouse model of arthritis and in some arthritis patients, pathogenic autoantibodies develop to the ubiquitous enzyme glucose-6-phosphate isomerase (GPI). Why the immune system only attacks joints has been a mystery. Benoist and colleagues show that nothing is unusual about GPI expression in the joint, however GPI from the bloodstream selectively settles on the joint’s articular surfaces. This exposed GPI serves as the target for the pathogenic autoantibodies of arthritic patients. In a second report, Wipke et al. show rapid (within minutes) deposition of anti-GPI in joints of mice infused with these pathogenic antibodies. This latter report confirms the Benoist paper in that even normal joints are coated with GPI. Benoist’s group identifies the second key to joint specificity: the inability of this tissue to regulate the activation of the inflammatory proteins called complement. Their activation on antibody-coated surfaces initiate a cascade of inflammatory responses – a good thing if there’s an infection, but deleterious to the health of a joint. Author contacts:
Christophe Benoist
Joslin Diabetes Center
Harvard Medical School, Boston
MA, USA
Tel: +1 617 264 2742
E-mail: cb@joslin.harvard.edu Paul Allen
Department of Pathology
Washington University School of Medicine
St. Louis, MO, USA
Tel: +1 314 362 8758
E-mail: allen@pathbox.wustl.edu Additional contact for comment on both papers: Toshio Hirano
Dept of Molecular Oncology
Graduate School of Medicine
Osaka University, Japan
Tel: +81 6 6879 3880
E-mail: hirano@molonc.med.osaka-u.ac.jp (C) Nature Immunology press release.
Message posted by: Trevor M. D'Souza
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