We conclude that the endothelial apoptosis and vascular collagen V interaction reinforce the vascular pathway in the SSc pathogenesis. Further studies are needed to determine whether this relationship is causal or consequential.

Although the fibrotic process is more intense in the SSc group, it does not affect the prognosis of these patients. Because the elastotic process is higher in the SSc group, this might suggest that autoimmune inflammatory mechanisms affecting the elastic fibre system play a greater role in the pathogenesis and pulmonary remodelling process of SSc NSIP than in idiopathic NSIP.

Abnormal collagen V fibres are overproduced in lungs from SSc patients and may play an important role in the pathogenesis of the disease as this molecule regulates tissue collagen assembly. The aberrant histoarchitecture observed in SSc can be related to the overexpression of the [alpha2(V)] gene of unknown origin.

Background: Interstitial lung disease is a well-recognized prognostic factor in systemic sclerosis (SSc). As the prognosis in nonspecific interstitial pneumonia (NSIP) has been described to be better in collagen vascular disorders compared to the idiopathic forms, we hypothesize that the mechanisms of repair and remodeling are different between these 2 forms of the disease. Objectives: To compare the mechanisms of repair and remodeling between SSc-associated NSIP and the idiopathic form, its impact on pulmonary function tests and survival rates. Methods: We analyzed 18 biopsies from patients with NSIP associated with SSc and 22 with idiopathic NSIP and compared the epithelial and vascular densities as well as vascular activity. Results: Epithelial cell density was lower in SSc-NSIP when compared with idiopathic NSIP (p < 0.0001). Type II pneumocytes and Clara cells were reduced in idiopathic NSIP (p = 0.02). A decrease in microvessel density was found in SSc-NSIP compared to idiopathic NSIP (p < 0.0001). The vascular activity measured by VCAM expression was higher in NSIP-SSc when compared to the idiopathic group (p < 0.0001). The DLCO/VA in SSc-NSIP was more compromised. A direct association between vascular density and DLCO/VA was found (p = 0.02). There was no difference in the survival rate between the 2 groups after a follow-up of 36 months. Conclusions: Alterations in the epithelium and vasculature seem to differ in the pathogenesis of SSc-NSIP when compared to the idiopathic form of the disease. Further studies may be required to assess the significance of these findings and explore if they can provide prognostic and/or treatment information.

Background: Pulmonary fibrosis is a frequent complication and a major cause of death in Systemic sclerosis (SSc); however, the pathogenesis is unclear and no safe and effective therapy exists The abnormal collagen deposition and the autoantibodies observed are significant important in this situation, in the last years we postulate that the pathogenetic mechanisms of the tissue fibrosis en SSc is mediate by collagen V alteration. Methods: We examined the amount of collagen V and mRNA chains expression using immunofluorescence, Real−time PCR and computer morphometric analysis in 15 open lung biopsies of patients with SSc without pulmonary hypertension. Normal lung tissue was obtained from 8 individuals who had died from traumatic injuries, as a control group. The pulmonary function tests were analyzed in theses cases and correlated with collagen amount and PCR chains expression. Results: The amount of collagen type V (45.28±13.21) in pulmonary interstitum was significance higher when compared with control (22.90±4.13) group (p<0.001). In SSc we found increase in both, alpha 1 (1.32±0.34) and 2 (0.86±0.19) chains mRNA expression when compared with alpha 1 (0.50±0.10) and 2 (0.11±0.05) chains of control group, being the proportion between alpha 1 and 2 chains of 2:1 in the control group not maintained in SSc. In fact, alfa 2 chain was more increased in SSc. Interestingly, a significant inverse association was found between collagen V VC (rs = −0.72; p=0.002), FCV (rs = −0.76; p<0.001) and FEV1 (rs = −0.89; p<0.001) pulmonary function tests. Conclusions: We concluded that pulmonary fibrosis in SSc probably occurs by abnormal collagen V chains mRNA synthesis reinforcing the participation of this collagen in pathogenesis of SSc and open new therapeutic perspectives for these patients. This abstract is funded by: FAPESP, CNPq. Am J Respir Crit Care Med 179;2009:A3942 Internet address: www.atsjournals.org Online Abstracts Issue