Particularities of the vasculature can promote the organ specificity of autoimmune attack

BA Binstadt, PR Patel, H Alencar, PA Nigrovic… - Nature …, 2006 - nature.com
BA Binstadt, PR Patel, H Alencar, PA Nigrovic, DM Lee, U Mahmood, R Weissleder
Nature immunology, 2006nature.com
How certain autoimmune diseases target specific organs remains obscure. In
the'K/BxN'arthritis model, autoantibodies to a ubiquitous antigen elicit joint-restricted
pathology. Here we have used intravital imaging to demonstrate that transfer of arthritogenic
antibodies caused macromolecular vasopermeability localized to sites destined to develop
arthritis, augmenting its severity. Vasopermeability depended on mast cells, neutrophils and
FcγRIII but not complement, tumor necrosis factor or interleukin 1. Unexpectedly …
Abstract
How certain autoimmune diseases target specific organs remains obscure. In the 'K/BxN' arthritis model, autoantibodies to a ubiquitous antigen elicit joint-restricted pathology. Here we have used intravital imaging to demonstrate that transfer of arthritogenic antibodies caused macromolecular vasopermeability localized to sites destined to develop arthritis, augmenting its severity. Vasopermeability depended on mast cells, neutrophils and FcγRIII but not complement, tumor necrosis factor or interleukin 1. Unexpectedly, radioresistant FcRγ-expressing cells in an organ distant from the joint were required. Histamine and serotonin were critical, and systemic administration of these vasoactive amines recapitulated the joint localization of immune complex–triggered vasopermeability. We propose that regionally distinct vascular properties 'interface' with immune effector pathways to foster organ-specific autoimmune damage, perhaps explaining why arthritis accompanies many human infectious and autoimmune disorders.
* Note: In the version of this article initially published online, the end of the third sentence of the second subsection of Results is incorrect. The sentence should read “Intravenous administration of preaggregated normal mouse IgG elicited an increase in joint-localized vasopermeability very similar to that induced by the administration of arthritogenic serum (Fig. 2b and data not shown).” Also, the final acknowledgement is incorrect; it should read “… and by the National Institute of Diabetes and Digestive and Kidney Diseases–supported Diabetes and Endocrinology Research Center cores of the Joslin Diabetes Center.” The errors have been corrected for the HTML and print versions of the article.
nature.com