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Urinary type II collagen helical peptide (HELIX-II) as a new biochemical marker of cartilage degradation in patients with osteoarthritis and rheumatoid arthritis.
Arthritis Rheum. 2005 Apr; 52(4):1081-90.AR

Abstract

OBJECTIVE

Type II collagen, which consists of a large helical domain and telopeptides at each end, is the most abundant protein of cartilage matrix. The aim of this study was to develop a biochemical marker reflecting the degradation of the helical region of type II collagen and to evaluate its clinical performance in patients with osteoarthritis (OA) and rheumatoid arthritis (RA).

METHODS

We developed a competitive polyclonal antibody-based enzyme-linked immunosorbent assay (ELISA) using the 622-632 peptide derived from the sequence of the alpha1 chain of human type II collagen (HELIX-II) as immunogen and standard. We measured urinary levels of HELIX-II peptide and C-terminal crosslinking telopeptide of type II collagen (CTX-II) in 90 patients with knee OA (73% women; mean +/- SD age 63.0 +/- 8.0 years, mean +/- SD disease duration 6.1 +/- 6.8 years), 89 patients with early RA (disease duration </=3 years) (79% women; mean +/- SD age 48.7 +/- 11.6 years), 25 patients with Paget's disease of bone (HELIX-II only), and 162 healthy controls. In RA patients, we investigated the relationships between baseline urinary HELIX-II and CTX-II levels and the progression of joint destruction as measured by the changes in the total Sharp score (average from 2 independent readers) over 1 year.

RESULTS

The intraassay and interassay variations of the HELIX-II ELISA were lower than 13% and 15%, respectively. The HELIX-II ELISA showed no significant cross-reactivity with human intact or denatured type II collagen, with the homologous peptides from human type I or type III collagens, or with HELIX-II peptides elongated (by 1 amino acid) or shortened (by 1 or 2 amino acids) at the C-terminal end, indicating that the HELIX-II ELISA recognized a neoepitope from the alpha1 chain of type II collagen. Median urinary HELIX-II levels were increased in patients with knee OA (by 56%; P < 0.0001) or early RA (by 123%; P < 0.0001) compared with those in age- and sex-matched healthy controls. Baseline urinary HELIX-II levels in the highest tertile were associated with an increased risk of radiographic progression in RA (increase in the total Sharp score >/=0.5 units/year), with an odds ratio (OR) of 5.9 (95% confidence interval [95% CI] 2.0-17.2) after adjustment for serum C-reactive protein (CRP) levels and baseline joint damage. Patients with increased levels of both urinary HELIX-II and CTX-II had the highest risk of progression (OR 17.5 [95% CI 3.1-99]).

CONCLUSION

The HELIX-II ELISA is specific for type II collagen degradation, has adequate technical performance, and can distinguish patients with knee OA or RA from healthy controls. Elevated HELIX-II levels are associated with increased risk of radiographic progression in RA independently of CRP levels, baseline joint damage, and urinary CTX-II levels. The HELIX-II ELISA should be useful for the clinical investigation of patients with arthritis and for identifying RA patients at higher risk of progression.

Authors+Show Affiliations

Synarc, Lyon, France.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15818703

Citation

Charni, Nadine, et al. "Urinary Type II Collagen Helical Peptide (HELIX-II) as a New Biochemical Marker of Cartilage Degradation in Patients With Osteoarthritis and Rheumatoid Arthritis." Arthritis and Rheumatism, vol. 52, no. 4, 2005, pp. 1081-90.
Charni N, Juillet F, Garnero P. Urinary type II collagen helical peptide (HELIX-II) as a new biochemical marker of cartilage degradation in patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 2005;52(4):1081-90.
Charni, N., Juillet, F., & Garnero, P. (2005). Urinary type II collagen helical peptide (HELIX-II) as a new biochemical marker of cartilage degradation in patients with osteoarthritis and rheumatoid arthritis. Arthritis and Rheumatism, 52(4), 1081-90.
Charni N, Juillet F, Garnero P. Urinary Type II Collagen Helical Peptide (HELIX-II) as a New Biochemical Marker of Cartilage Degradation in Patients With Osteoarthritis and Rheumatoid Arthritis. Arthritis Rheum. 2005;52(4):1081-90. PubMed PMID: 15818703.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urinary type II collagen helical peptide (HELIX-II) as a new biochemical marker of cartilage degradation in patients with osteoarthritis and rheumatoid arthritis. AU - Charni,Nadine, AU - Juillet,Fabrice, AU - Garnero,Patrick, PY - 2005/4/9/pubmed PY - 2005/5/13/medline PY - 2005/4/9/entrez SP - 1081 EP - 90 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 52 IS - 4 N2 - OBJECTIVE: Type II collagen, which consists of a large helical domain and telopeptides at each end, is the most abundant protein of cartilage matrix. The aim of this study was to develop a biochemical marker reflecting the degradation of the helical region of type II collagen and to evaluate its clinical performance in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: We developed a competitive polyclonal antibody-based enzyme-linked immunosorbent assay (ELISA) using the 622-632 peptide derived from the sequence of the alpha1 chain of human type II collagen (HELIX-II) as immunogen and standard. We measured urinary levels of HELIX-II peptide and C-terminal crosslinking telopeptide of type II collagen (CTX-II) in 90 patients with knee OA (73% women; mean +/- SD age 63.0 +/- 8.0 years, mean +/- SD disease duration 6.1 +/- 6.8 years), 89 patients with early RA (disease duration </=3 years) (79% women; mean +/- SD age 48.7 +/- 11.6 years), 25 patients with Paget's disease of bone (HELIX-II only), and 162 healthy controls. In RA patients, we investigated the relationships between baseline urinary HELIX-II and CTX-II levels and the progression of joint destruction as measured by the changes in the total Sharp score (average from 2 independent readers) over 1 year. RESULTS: The intraassay and interassay variations of the HELIX-II ELISA were lower than 13% and 15%, respectively. The HELIX-II ELISA showed no significant cross-reactivity with human intact or denatured type II collagen, with the homologous peptides from human type I or type III collagens, or with HELIX-II peptides elongated (by 1 amino acid) or shortened (by 1 or 2 amino acids) at the C-terminal end, indicating that the HELIX-II ELISA recognized a neoepitope from the alpha1 chain of type II collagen. Median urinary HELIX-II levels were increased in patients with knee OA (by 56%; P < 0.0001) or early RA (by 123%; P < 0.0001) compared with those in age- and sex-matched healthy controls. Baseline urinary HELIX-II levels in the highest tertile were associated with an increased risk of radiographic progression in RA (increase in the total Sharp score >/=0.5 units/year), with an odds ratio (OR) of 5.9 (95% confidence interval [95% CI] 2.0-17.2) after adjustment for serum C-reactive protein (CRP) levels and baseline joint damage. Patients with increased levels of both urinary HELIX-II and CTX-II had the highest risk of progression (OR 17.5 [95% CI 3.1-99]). CONCLUSION: The HELIX-II ELISA is specific for type II collagen degradation, has adequate technical performance, and can distinguish patients with knee OA or RA from healthy controls. Elevated HELIX-II levels are associated with increased risk of radiographic progression in RA independently of CRP levels, baseline joint damage, and urinary CTX-II levels. The HELIX-II ELISA should be useful for the clinical investigation of patients with arthritis and for identifying RA patients at higher risk of progression. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15818703/Urinary_type_II_collagen_helical_peptide__HELIX_II__as_a_new_biochemical_marker_of_cartilage_degradation_in_patients_with_osteoarthritis_and_rheumatoid_arthritis_ L2 - https://doi.org/10.1002/art.20930 DB - PRIME DP - Unbound Medicine ER -