I guess thats a fair question.. I dont believe that the article bothered to answer that question! But dont be surprised, this is a journalists writing (i think). But you can be certain that it has something to do with our genes, ie your genes make you susceptible.
Start by going to the source of the article :
http://www.arthritis.org/resources/news/carbohydrates_ra.asp"" High levels of GAG (glycosaminoglycans), she says, could be caused by bacteria, which produce enzymes that break down connective tissue, releasing the carbohydrates. And many bacteria and other organisms produce GAG on their cell surfaces, she says, so the immune response to an invading microbe, may mistakenly discern GAG in healthy cartilage as another invader. ''That might explain why so many infections can lead to arthritis,'' she says""
I think most rheumatologists agree that there is an unknown trigger factor - otherwise why is the desease starting later in life, why not have inflammation since birth?
Anyways, dont lose sight of the infectious root of AS :-). The following journal articles talk about how rodent studies have shown that AS really is initiated by an infection. Why?, because rodents bred with HLA B27+ do not get the desease until removed from a pathogen free environment !!
Keywords used in my search queries on pubmed:
- transgenic rodent / rat spondylitis HLA B27
###################################################################
Journal of Experimental Medicine, Vol 182, 1153-1158, Copyright © 1995 by Rockefeller University Press
Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin: a model of human spondyloarthropathies
SD Khare, HS Luthra and CS David
Department of Immunology, Mayo Clinic and Medical School, Rochester, Minnesota 55902, USA.
Human class I major histocompatibility complex allele HLA-B27 is associated with a group of human diseases called "spondyloarthropathies." Studies on transgenic rats expressing HLA-B27 and human beta 2-microglobulin have confirmed the role of HLA-B27 in disease pathogenesis. Here we report spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin (B27+ beta 2m-/- ). In the absence of beta 2-microglobulin, B27+ beta 2m-/- animals do not express the HLA-B27 transgene on the cell surface and have a very low level of CD8+ T cells. Most of the B27+ beta 2m-/- male mice showed nail changes, hair loss, and swelling in paws, which leads to ankylosis.
The symptoms occur only after the B27+ beta 2m-/- mice are transferred from the specific pathogen-free mouse colony. These results suggest that aberrant assembly, transport, and expression of the HLA- B27 molecule may predispose an individual for development of the disease when exposed to an appropriate environmental trigger. http://www.jem.org/cgi/content/abstract/182/4/1153###################################################################
Journal of Experimental Medicine, Vol 180, 2359-2364, Copyright © 1994 by Rockefeller University Press
The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats
JD Taurog, JA Richardson, JT Croft, WA Simmons, M Zhou, JL Fernandez-Sueiro, E Balish and RE Hammer
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235.
A number of inflammatory disease states occur with greatly increased frequency in individuals inheriting the human major histocompatibility complex class I allele HLA-B27.
In a minority of cases, namely those with B27-associated reactive arthritis, there is good evidence that the disease state is triggered by infection with an enteric or genitourinary bacterial pathogen. For the majority of B27-associated disease, no definite pathogenetic role for bacteria has been established. However, in these latter cases intestinal inflammation can often be demonstrated, and it sometimes occupies a major part of the clinical picture. Rats transgenic for B27 are known to develop a disorder resembling B27-associated human disease, with prominent intestinal, joint, skin, and male genital inflammatory lesions.
We report here that B27 transgenic rats raised in a germfree environment do not develop inflammatory intestinal or peripheral joint disease, whereas the skin and genital inflammatory lesions are unaffected by the germfree state. These findings support the concept that gut and joint inflammation are pathogenetically closely related, and they provide direct evidence that the commensal gut flora play an important role in the pathogenesis of B27-associated gut and joint inflammation. http://www.jem.org/cgi/content/abstract/180/6/2359###################################################################
http://www.mult-sclerosis.org/news/Nov2001/FullTextAnimalModelsOfAutoimmuneDiseases.htmlThe first spontaneous disease models that expressed a human HLA were HLA-B27–Tg rats and mice (6, 7).
When animals are moved from pathogen-free environments to conventional colonies, animals from both species develop spondylitis-like features, which indicates that the onset of the disease requires an environmental trigger. The disease primarily affects male rodents, as with the human disease. These models confirmed that the gene encoding HLA-B27 itself, and not other closely linked genes, is responsible for spondylitis. But the model also generated controversies and additional questions. Why did the B27-Tg rats require more than 100 copies of the genes encoding HLA-B27 and human b2-microglobulin (b2M) for the onset of disease and why did HLA-B27 mice develop disease only in the absence of the mouse b2M? Studies in mice have suggested that the B27 molecule may reach the cell surface as an empty or free heavy chain in the absence of b2M and present an exogenous antigen to activate autoreactive T cells. Data from studies on human cells have shown that b2M-free B27 homodimers are transported to the cell surface and have the capacity to load exogenous peptides (8). These homodimers resemble a class II molecule that can present peptides in a classical class II antigen-processing pathway. Thus, the studies in rodent models and humans are converging in delineating spondylitis.
###################################################################
Pronase and Papain: the following medical journal article seems to indicate that they damaged / destroyed the Klebsiella organisms "modifying factor". Which I assume would have a very very positive effect on our desease.
This study showed
Klebsiella having a "modifying factor" reacting with HLA-B27 lymphocytes and other cells. "Pronase and papain destroyed the modifying factor activity whereas trypsin and alpha-chymotrypsin degraded the factor into smaller fragments without destroying its ability to modify B27 AS- lymphocytes."I took this article from:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3539895&dopt=Abstract
