| Markers of collagen metabolism in the assessment of rheumatoid arthritis.: With special reference to cross-linked carboxyterminal telopeptide of type I collagen (ICTP) | ||
|---|---|---|
| Prev | Chapter 2. Review of the literature | Next |
A radioimmunoassay for human PICP was first described in 1974 (Taubman et al.). The molecular weight of the propeptide is 100 kd, and two main bands of about 30 kd each appear after reduction. The propeptide was first thought to be derived from the aminoterminal end of type I procollagen, but was later identified as a carboxypeptide. Elevated serum levels have been found in patients with Paget’s disease (Simon et al. 1984) and various liver diseases (Savolainen et al. 1983). The elevated values observed in Paget’s disease correlated with the extent and activity of the disease as determined by serum alkaline phosphatase (Partiff et al. 1987). Exogenous hormone treatment elevated the serum PICP concentrations in growth hormone-deficient children (Carey et al. 1985). A low rate of type I collagen synthesis, as assessed by PICP in serum, has been previously reported in RA (Kröger et al. 1993)
The aminoterminal propeptide of type I procollagen contains a collagenous domain and thus has the shape of a short rod with a more globular part at the end. The molecular mass of the propeptide is about 35 kd. The circulating antigenicity related to PINP can be resolved into two peaks with different molecular sizes, the first of which is identical to the free, authentic trimeric antigen, while the latter resembles part of a single domain of the pro-α1(I) chain of PINP (Melkko et al. 1996). The origin of the smaller forms of PINP is most probably the degradation of newly synthesized type I procollagen or type I pN-collagen with the retained propeptide. Thus, the exclusive assay of intact PINP seems to be more sensitive than total PINP for detecting changes in the rate of bone collagen synthesis (Risteli & Risteli 1999). For instance, estrogen treatment in postmenopausal women leads to a 42% decrease in the circulating concentrations of intact PINP, compared with the 30% decrease observed with an assay measuring both antigenic forms (Suvanto-Luukkonen et al. 1997). In postmenopausal women with hormone replacement therapy, the changes in intact PINP were twofold compared to those in PICP (Sharp et al. 1996). In a study where 206 pre- and postmenopausal breast cancer patients with nonmetastatic disease were followed up for two years, an increase in the concentration of intact PINP at 12 months predicted a further loss of BMD at 24 months (Saarto et al. 1998).
The aminoterminal propeptide of type III procollagen is an elongated molecule with an overall molecular mass of 42 kd that consists of three identical polypeptide chains linked by disulphide bonds. The elongated shape of PIIINP is due to the fact that the central part of PIIINP contains a collagen-like triple helix, where every third amino acid is glycine and where several hydroxyproline residues are also located. PIIINP resembles PINP in overall structure (Risteli et al. 1993).
The helical domain of PIIINP can be digested away with bacterial collagenase. The different parts of PIIINP are conventionally named according to their elution positions in gel filtration after such digestion. The aminoterminus, known as Col 1, is the most immunogenic region in the molecule, while most anti-PIIINP antibodies recognize the antigenic determinants present in this part (Risteli et al. 1993).
The serum concentrations of PIIINP were elevated in active RA and showed some correlation with the clinical and serological signs of disease activity (Hørslev-Petersen et al. 1986, Hørslev-Petersen et al. 1988a). Inflammatory synovial fluid (SF) contains large amounts of PIIINP (Gressner et al. 1984, Hørslev-Petersen et al. 1988). The high SF:S PIIINP ratios found in such patients suggest local production and release of the protein from the joint via lymphatics into the circulation (Hørslev-Petersen et al. 1988b, Jensen et al. 1993).