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. 2007 Feb 7;1:61–76.

Table 2.

Currently available biomarkers of type II collagen degradation and synthesis.

Biomarker Namea AA Sequence AA Residuesb Specificityc Body Fluid or Tissued Abe BIPED Classificationf References Related to Assay Development
Collagen Degradation
Cleavage Neoepitopes
Col2-1/4N1 LAGQRG 907–912 Not specified C p(Fab)2 I (Billinghurst et al., 1997)
Col2-1/4N2 QRGIVG 910–915 CII C p(Fab)2 I (Billinghurst et al., 1997)
C1,2C (COL2-3/4Cshort) GPP(OH)GPQG 899–906 CI and CII S, SF, C p P (combined with C2C or CPII), D (Billinghurst et al., 1997)
C2C (COL2-3/4Clong mono) E GPP(OH)GPQG 898–906 CII in humans S, SF, U m P (combined with C1,2C Or CPII), E, D (Poole et al., 2004)
uTIINE (5109 and 9A4 ELISA; 5109 capture in LC-MS/MS format) GEPGDDGPS/GPPGPQG;ARGDSGPPGRAGEPGLQGPAGPPGEKGEPGDDGPSGAEGPPGPQG 888–896/899–906; 862–906 CII U m/m; m/LC-MS/MS B, P, E, D (Otterness et al., 1999, Downs et al., 2001, Burgeson and Nimni, 1992, Hellio Le Graverand et al., 2006)
Denaturation Neoepitopes
COL2-3/4m APGEDGRPGPPG 511–522 CII, CXI C, S m D (Hollander et al., 1994)
Coll 2-1
Coll 2-1 NO2 		HRGYPGLDG 220–228 CII S, U p P, D (Deberg et al., 2002, Henrotin et al., 2004)
Helix-II∞ ERGETGPP(OH) GTS 754–764 CII U p P, D (Charni et al., 2005)
AH12 GAPGPQGFQGNPGEPGEPGVS 147–167 CII C p I (Croucher and Hollander, 1999)
AH8 GPPGPPGKPGDDGEAGKPGKA 174–194 CII C m and p I (Croucher and Hollander, 1999)
AH9 GPP(OH)GP RGRSGETGPAGPP(OH)GNP(OH) 1116–1136 CII C p I (Croucher and Hollander, 1999)
CII CNBr9.7 (18:6:D6 and 14:7:D8 ELISA) Epitope within CNBr 9.7/GPQGPRGDKGEAGEP 1028–1151/1041–1055 CII/CI, CII, CIII, CV SF m/m D (Barrach et al., 1996, Elsaid and Chichester, 2006)
Telopeptide Epitopes
col2CTx g
CTX-II (Urine CartiLaps and preclinical serum assay) g 		(R)EKGPDP 1160–1166 CII cross-links C, S, P(EDTA), SF, U m, m/m B, P, E, D (Eyre, 1991, Christgau et al., 2001, Oestergaard et al., 2006, Matyas et al., 2004, Eyre, 1989)
Collagen Synthesis
CPII PIICP (chondrocalcin) Sequence within C-propeptide: DQAAGGLR Q…DIGPVCFL 1173–1418 (of procollagen IIB in Figure 1a or 1242–1487 in procollagen IIA in Figure 1b) CII S, SF, C p p/p B, P, E, D (Van der Rest et al., 1986, Sugiyama et al., 2003, Mansson et al., 1995, Shinmei et al., 1993)
PIIANP QEAGSCVQDG QRYNDKDVW KPE PCRICVCDTGT VLCDDIICEDV KDCLSPEIPFG ECCPICPTDLA TAS 29–97 (of procollagen IIA in figure 1b) CII S (not plasma) p P (combined with uCTXII), E, D (Oganesian et al., 1997, O’Leary et al., 2004)
a

The biomarker name is the usual one in the literature and does not discriminate if it applies to an antibody, an epitope, or an assay name.

b

Categories are based on localization of an epitope in the type II collagen molecule and residue numbering is based on the human type II collagen sequence, P024588 in UniProtKB/Swiss sequence shown in Figure 1a:

  • -Cleavage neoepitopes localized to the collagenase cleavage site between Gly906 and Leu907
  • -Denaturation neoepitopes localized to the triple-helical domain
  • -Epitopes localized to the telopeptides
  • -Collagen synthesis epitopes localized to the N-propeptide domain (AA 26–112) or C-propeptide domain (AA 1173–1418).
c

CII = type II collagen; CI = type I collagen; CIX = type IX collagen.

d

The table shows human body fluid or tissue for which the application of the assay is documented in the literature: S = serum; SF = synovial fluid; U = urine; C = cartilage explant.

e

m - monoclonal antibody (mAb), p - polyclonal antiserum, m/m - a sandwich of two mAbs, LC-MS/MS - liquid chromatography with mass spectroscopy.

f

Provisional BIPED classification categories based on Bauer et al. (Bauer et al. 2006): B = burden of disease; I = investigative; P = prognostic; E = efficacy of intervention; D = diagnostic marker.

g

The antibodies to Col2CTx and CTX-II are specific for a peptide that happens to be present in the cross-linked structure in human body fluids but the cross-link is not a part of the epitope.