pathogenesis of arthritis... single organ AI disease

[Guest guest]

This pertains to my discussion on arthritis causes with Norman.

The authors also suggest it could help explain why autoreaction to

widely-distributed autoantigens might be be able to cause single-

organ pathology (which is currently a paradox). But I dont find this

claim of theirs strikingly believable.

It seems Ab against an antigen which is found (in equal abundance?)

throughout the mouse causes arthritis without causing other

observable pathos.

This lends credence toward the proposal that some arthritides could

be sustained by deposition of alloantigens from chronic infection

*outside* the afflicted joint, an idea I have formerly considered

somewhat akward. It could also be due to autoantibodies.

=================

Nat Immunol. 2006 Mar;7(3):284-92. Epub 2006 Jan 29. Related

Articles, Links

Particularities of the vasculature can promote the organ specificity

of autoimmune attack.

Binstadt BA, Patel PR, Alencar H, Nigrovic PA, Lee DM, Mahmood U,

Weissleder R, Mathis D, Benoist C.

[1] Harvard Medical School, Boston, Massachusetts 02115, USA. [2]

Section on Immunology and Immunogenetics, Joslin Diabetes Center,

Boston, Massachusetts 02215, USA. [3] Rheumatology Program,

Children's Hospital Boston, Boston, Massachusetts 02115, USA.

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 FcgammaRIII

but not complement, tumor necrosis factor or interleukin 1.

Unexpectedly, radioresistant FcRgamma-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.

PMID: 16444258 [PubMed - in process]

[Guest guest]

That was from eurolyme by the way.