Background/Purpose:

Catabolism of type II collagen (COLII) involves multiple metalloproteinases, aggrecanases and cathepsin, releasing heterogeneous triple helix cleavage products. The complex regulation of these enzymes and of inducible NOS (iNOS)includes inflammatory cytokines. Col2-1 peptide (Col), located towards the N-telopeptide region of COLII contains a tyrosine residue susceptible to endogenous nitration by reactive nitrogen species, forming Col-2-1-NO2 (NCol). Specific immunoassays allow for estimation of nitration index (NI). Using these assays in OA and RA should show differences since RA, unlike OA, is treated with DMARDs known to inhibit structural damage progression.

Methods:

Serum (S) and Urine (U) Col and NCol were measured by ELISA in a cross-sectional study (49 RA and 118 outpatients with active hand OA). The ratio of NCol (nmol)/Col (nmol) provided NI. Clinical variables were age, sex, DAS and VAS. Urinary fractional excretions (UFE) of biomarkers was calculated in RA patients.Statistical analysis used STATA® Version 12.1

Results:

OA patients were older (64 years vs 58 in RA). Mean DAS28 was 2.64 with 60% receiving corticoids or synthetic and biological DMARD treatment in RA. VAS pain was higher in OA than RA patients (46 vs. 34;p<0.0001). Mean SCol concentrations (nmol/l) and SNCol (pmol/l) were higher in RA (308±17 and 687 ±90) than OA (241 ± 13 and 465±39; p<0.0001). Mean UCol (nmol/mmol creatinine) was higher in RA than in OA (16.3 vs. 8.1; p<0.0001) whereas UNCol (pmol/mmol creatinine) values were similar between the 2 groups (22.4 ±4.3 in RA and 26.2 ±2.1 in OA; p>0.1). Col and NCol UFE were 2.87% (2.25-3.48; 95%CI) in RA and 2.63 % (1.81-3.46; 95%CI) and highly correlated (r-square=0.53; p<0.0001).The SCol2-1NI was similar in RA (0.238 %, 95% CI: 0.214-0.262) and in OA (0.217, 95% CI: 0.19-0.24; p>0.05) but the UCol2-1NI was markedly lower in RA (0.164, 95%CI: 0.141-0.187) than OA (0.37, 95%CI: 0.33-0.42; p<0.0001). In both RA and OA, pairwise comparisons of serum and urine NI indicated highly significant differences ( p<0.0001). None of the disease activity indices were associated with any of the two biomarkers or their ratios in serum or urine.

Conclusion:

Data indicate excess nitrated forms of Col2-1 in the urine of patients suffering from active OA in comparison to DMARD treated RA patients, indicating that a greater proportion of OA SNCol immunoreactive forms pass through the renal glomerular membrane than in RA. In RA, fractional excretion of both Col and NCol was low and similar for Col and NCol, excluding a differential renal handling of the detected epitopes. The excess of urinary nitrated forms in OA vs RA may result from the OA disease process itself or from DMARD interference with the iNOS activity in RA. Within patients’ differences between serum and urine NI values indicate biological heterogeneity of immunoreactive species containing the Col2-1 epitope. The clinical relevance of this heterogeneity is unknown since the half-life of measured components have not been studied. Additional investigations with specific enzyme inhibitors in OA and biological DMARDs in early RA are warranted to quantify the dynamics of serum and urine components of Col2-1 and its nitrated forms.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunoreactive-collagen-type-ii-cleavage-products-and-their-nitrated-forms-in-rheumatoid-arthritis-and-osteoarthritis-an-outpatient-cross-sectional-study/