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SAT0317 Type vi collagen formation: a new objective blood-based marker reflecting fibrosis of the skin in systemic sclerosis
  1. P Juhl1,
  2. L Iversen2,
  3. T Karlsmark2,
  4. M Karsdal1,
  5. A-C Bay-Jensen1,
  6. M Mogensen2,
  7. AS Siebuhr2
  1. 1Nordic Bioscience, Herlev
  2. 2Department of dermatology, Bispebjerg Hospital, Copenhagen, Denmark

Abstract

Background Systemic sclerosis (SSc) is characterized by fibrosis of the skin. The dermis of the skin is rich in type I and III collagen, but other collagens as type VI collagen are present in the skin and play a key role in the organization of type I and III collagen. There is a lack of objective disease activity markers in SSc for frequent assessment of patients. The only measurement of disease activity currently is the subjective modified Rodnan skin score (mRSS).

Objectives The objective is to examine blood-based markers of type I, III, and VI collagen formation as surrogates of disease activity and fibrosis in SSc.

Methods SSc patients fulfilling the ACR criteria (n=121) were included. The study included both limited SSc (lSSc, n=79) and diffuse SSc (dSSc, n=42) (approval number H-B-2008–131). Markers of type I, III and VI collagen formation (P1NP, PRO-C3 and PRO-C6, respectively) were measured in serum by ELISA. Difference in the markers between groups were tested by Mann-Whitney T test and correlations were assessed by multiple linear regression adjusting for age, gender and BMI. Discriminative power of the markers was analyzed by ROC AUC on tertiles of mRSS.

Results There were no significant difference in gender, BMI or disease duration between lSSc and dSSc. The mean age of the population was 57.4 (SD 11.6) years, 84% were female, mean disease duration was 11.7 (SD 8.9) years and mean mRSS was 11.2 (SD 8.6).

PRO-C3 and PRO-C6 were significantly higher early (<4 years) dSSc compared to early lSSc patients (both p=0.006). PRO-C6 was significantly elevated in early dSSc compared to late dSSc (p=0.04) and increased in late dSSc compared to late lSSc (p=0.02; Figure). Both PRO-C3 and PRO-C6 correlated with mRSS when adjusted for age, gender, and BMI with R-partial of 0.36 (p=0.0001) and 0.29 (p=0.002), respectively.

Both PRO-C3, and PRO-C6 could separate the patient group having the highest tertile of mRSS from the rest with an AUC (95% CI) of 0.73 (0.62–0.82), and 0.74 (0.63–0.83), respectively. Together, PRO-C3 and PRO-C6 could separate the groups with an AUC (95% CI) of 0.77 (0.67–0.86) (Table 1).

PRO-C3 and PRO-C6 performed equally well for identification of patients with the highest skin score (highest tertile vs. the middle and lower tertile) with a relative risk of 2.3 (1.4–3.8) (Table 2). The risk of being in the highest tertile of mRSS compared to the lowest were significantly higher with a high PRO-C6 (relative risk 2.6, 95% CI: 1.3–5.2) compared to PRO-C3 (relative risk: 2.2, 95% CI: 1.2–3.8) (Table 2).

Table 1
Table 2

Conclusions Markers reflecting fibrosis (measures of type III and VI collagen formation) could be novel objective, and potentially predictive, biomarkers of disease activity and severity.

Disclosure of Interest None declared

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