THU0242   COLLAGEN DEGRADATION PRODUCTS AND INFLAMMATORY ACTIVITY IN SYSTEMIC AND LOCALIZED SCLERODERMA

R. Becvar1, H. Hulejova2, M. Braun2, J. Stork3
1Outpatient dept, 2Connective tissue research lab, Institute of Rheumatology, 3Clinic of dermatovenerology, General Teaching Hospital, Praha 2, Czech Republic

Background: There are no simple and relevant activity markers for scleroderma as acute phase reactants do not reflect its activity. During the activation of immune system the increased production of certain proinflammmatory cytokines occurs among other IL-6 and sIL-2R (Kahaleh and LeRoy, 1989). In the fibrotic phase of SSc a massive deposition of collagen and elastin fibrils occurs which leads to an impaired equilibrium in formation and degradation of these fibrous proteins. The collagen turnover can be reflected in in urine by excretion of its cross-links pyridinoline and deoxypyridinoline, and metabolism of elastin can be monitored by excretion of desmosine and isodesmosine.
Objectives: The aim of this study was to assess the degradation of collagen type I and proinflammatory cytokines in systemic and localized scleroderma compared with psoriasis and healthy controls.
Methods: Total 99 individuals were examined – 24 with systemic sclerosis (SSc), 22 with localized scleroderma (LSc), 39 patients with psoriasis vulgaris (PsV) and 14 healthy controls. Urinary excretion of pyridinoline (U-PD) and deoxypyridinoline (U-DPD) were measured using sensitive isocratic HPLC method. Serum levels of interleukin-6 (IL-6) and and soluble interleukin-2 receptor (IL-2R) were assayed using commercial ELISA kits.
Results: In SSc group U-PD and U-DPD levels (nmol/mmol creat.) were increased compared with controls (p 0.001) and with PsV (p 0.006). IL-6 levels were increased compared with controls (p 0.004) and with PsV (p 0.002). IL-2R concentrations were insignificantly increased in comparison with controls and were lower than in PsV but the difference was not significant. In LSc group excretion of U-PD and U-DPD did not differ from controls, but were insignificantly decreased compared with PsV. IL-6 levels were increased compared with controls (p 0.001) and also with PsV (p 0.03). IL-2r concentrations were significantly increased in comparison only with controls (p 0.03).

Conclusion: In patients with SSc our data have shown the most intensive collagen degradation and simultanously an active inflammation as documented by IL-6 which reflects the pathological processes in the skin and visceral organs, compared with PsV patients and healthy inviduals. In LSc group collagen degradation was similar to that in control groups but a certain inflammatory activity was observed.
This work was supported by the Ministry of Healthcare research grant No. NR/7886-3.

References: 1. Becvar, R., Stork, J., Pesakova, V. et al. (2005) Clinical correlations of potential activity markers in systemic sclerosis. Ann. N. Y. Acad. Sci. 1051, 404-412.
2. Brinckmann, J., Neess, C.M., Gaber Y et al. (2001) Different pattern of collagen cross-links in two sclerotic skin diseases: lipodermatosclerosis and circumscribed scleroderma. J. Invest. Dermatol. 117, 269-273.
3. Farber, E.M., Raychaudhuri, S.P. (1999) Is psoriasis a neuroimmunologic disease? Int .J. Derm., 38, 12-15.
4. Istok, R., Bely, M., Stancikova, M., Rovensky, J. (2001b) Evidence for increased pyridinoline concentration in fibrotic tissues in diffuse systemic sclerosis. Clin. Exp. Dermatol., 26, 545-547.
5. Ištok, R., Czirják, L., Lukáč, J. et al. (2001a) Increased urinary pyridinoline cross-link compound of collagen in patients with systemic sclerosis and Raynaud’s phenomenon. Rheumatology, 40, 140-146.