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Circulating Protein Fragments of Cartilage and Connective Tissue Degradation Are Markers of Rheumatoid Arthritis and Ankylosing spondylitis

pattismith

Senior Member
Messages
3,931
Circulating Protein Fragments of Cartilage and Connective Tissue Degradation Are Diagnostic and Prognostic Markers of Rheumatoid Arthritis and Ankylosing Spondylitis
  • Anne C. Bay-Jensen ,
  • Stephanie Wichuk,
  • Inger Byrjalsen,
  • Diana J. Leeming,
  • Nathalie Morency,
  • Claus Christiansen,
  • Morten A. Karsdal,
  • Walter P. Maksymowych


Abstract

Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS). Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions.

Type II collagen is the primary structural protein of cartilage and type III collagen of connective tissues, and obvious targets for the collagenalytic, which increase during tissue inflammation.

The objective of the study was to investigate the diagnostic and prognostic utility of cartilage, C2M, and synovial, C3M, turnover biomarkers in AS.

Serum samples were retrieved from patients suffering from AS (n = 103), RA (n = 47) and healthy controls (n = 56). AS progressors were defined as having new vertebral syndesmophytes or more that 3 unit change in mSASSS over a two-year period. Type II collagen degradation markers in serum were measured by the C2M ELISA, and type III collagen degradation by the C3M ELISA. Logistic regression and dichotomized decision tree were used to analyze the prognostic value of the markers individually or in combination.

Both C2M and C3M levels were significantly higher in RA patients than in healthy controls (p<0.0001).

Diagnostic utility was analyzed by ROC and areas under the curve (AUCs) were 72% and 89% for C2M and C3M, respectively.

Both C2M and C3M, were significantly higher in serum samples from AS patient than from healthy controls (p<0.0001).

The AUCs of C2M and C3M, respectively, were 70% and 81% for AS. A combination of C2M and C3M, dichotomized according to best cut-offs for individual markers, could correctly identify 80% of the progressors and 61% of the non-progressors. The present study is the first to show that specific biomarkers of cartilage and connective tissue degradation facilitate both diagnosis and prediction of progression of RA and AS.
 

Sidny

Senior Member
Messages
176
Very interesting!

type III collagen of connective tissues, and obvious targets for the collagenalytic, which increase during tissue inflammation.

The question is, what could be driving the inflammation of these tissues? Could it be chronic infection of these structures with persistent pathogens?


Given what we know about how HSV increases the expression of MMP-9, Coxsackie Virus B infecting fibroblasts (a collagen producing cell) not to mention how Lyme is known to degrade connective tissues as well as the innumerable associations between the activity of other pathogens and connective tissue degradation I’m surprised diseases like RA and AS are still being referred to autoimmune vs infectious.

It’s interesting how a large number of infectious assaults/foreign agents could be upstream of and possibly trigger conditions like CCI/RA. It sounds to me by the nature of the descriptions of diseases like RA and AS that the underlying processes could be quite similar to CCI. Thanks for posting.
 
Last edited:

pattismith

Senior Member
Messages
3,931
@Sidny
I also thought it would be interesting to test fragments of connective tissue in blood of CFS/ME, Fibro and some other diseases to investigate if connective tissue degradation is part of the mechanism, and if the result can serve as markers