Circulating type I collagen degradation products: a new serum marker for clinical severity in patients with scleroderma?

Abstract

Systemic sclerosis (SSc; scleroderma) results in the excessive deposition of extracellular matrix components in affected organs. This is partly due to enhanced synthesis; however, the role of degradative processes in this disease is still poorly understood. Sera of 32 patients with SSc (22 with the diffuse, 10 with the limited form) and of six patients with morphoea were assessed using radioimmunoassays for the cross-linked carboxy terminal telopeptide of type I collagen (ICTP) and for the amino terminal propeptide of type I procollagen (PINP) reflecting type I collagen degradation and synthesis, respectively. In 27 of the 32 patients with SSc, the concentration of ICTP was above the upper limit of the normal value (4.6 micrograms/L) and the mean level was clearly elevated at 7.92 micrograms/L. The ICTP concentration correlated with the skin score measuring the extent of the lesions, whereas no such correlation was found for PINP. The ICTP antigen in serum, studied by immunoblotting, had a molecular weight of about twice that of the trypsin-generated fragment isolated from human bone collagen. The mean concentration of serum PINP was 43.9 micrograms/L and no patient exceeded the upper limit of the normal range (80 micrograms/L). We report here for the first time that the concentration of the type I collagen degradation product ICTP in serum shows a close correlation with the extent of skin fibrosis in patients with SSc. We conclude that the increased deposition of type I collagen in this disease is accompanied by an increased turnover of this molecule, indicating a more complex derangement of synthetic and degradative processes than previously acknowledged.

Losartan therapy for Raynaud's phenomenon and scleroderma: Clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial

“…The observed reduction in serum levels of PINP among patients in our study, reflecting the down-regulation of collagen synthesis, was statistically significant in the losartan group. Serum markers of collagen turnover may reflect fibrotic disease activity (40,41), raising the possibility that losartan might have additional diseasemodifying potential in SSc, although such a conclusion would be premature from the current study.…”

Serum Markers of Type I Collagen Synthesis and Degradation in Amyotrophic Lateral Sclerosis

“…ICTP has been demonstrated in suction blister obtained from human skin by Western blot analysis [7]and by radioimmunoassay [39]and it can be detected immunohistochemically throughout the dermis of adult human skin using the same antibody as in the radioimmunoassay [7]. ICTP is cleared rapidly from the human circulation by the kidney, and renal failure may influence the values [36].…”

“…in multiple myeloma [36], osteolytic bone metastases [40]or rheumatoid arthritis [38]. Increased serum concentrations of ICTP have also been noted under conditions associated with systemic sclerosis [7], generalized morphea [7], chronic liver disease [41], Graves’ disease [42], and primary hyperparathyroidism [43]. Since neither ALS patients nor control groups A and B had the above conditions and disorders, a metabolic alteration in type I collagen may take place in ALS.…”

“…Type I collagen is the most abundant collagen type in many soft tissues and accounts for over 90% of the organic matrix of bone [6]. Type I collagen accounts for 80–85% and type III collagen for 10–15% of the total skin collagen [7]. Modulation of collagen metabolism is thus clinically important.…”

Biomarkers in Systemic Sclerosis

“…The increased expression of the genes encoding interstitial collagens types I and III and the marked elevation of the production of the corresponding proteins in SSc led to numerous studies investigating circulating or urinary levels of collagen molecules or collagen fragments as www.futuremedicine.com biomarkers that may reflect the activity of the ongoing fibrotic process [104][105][106][107][108][109]. The serum levels of the telopeptide corresponding to the crosslinked carboxy-terminal end of type I collagen, as well as the amino-terminal propeptide of type I procollagen, have been given substantial attention as they reflect the degradation and synthesis of type I collagen, respectively.…”