Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Abnormal Morphology and Excessive Synthesis of Collagen V Affects Skin Thickness and Disease Activity in Systemic Sclerosis.
Martin1, Patricia, Teodoro1, Walcy R., Velosa2, Ana Paula P., de Morais1, Jymenez, Carrasco3, Solange, Braga1, Francine F. R., Christmann4, Romy
Universidade de São Paulo, São Paulo, Brazil
Univerdidade de São Paulo, São Paulo, Brazil
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
Boston University, Boston, MA
University of São Paulo, São Paulo, Brazil
Background/Purpose:
Physiological and mechanical properties of skin, one of the primary organs affected in systemic sclerosis (SSc), depends on collagen types I, III and V assembly, forming heterotypic fibers. Collagen V (COLV) regulates fibril diameter and maintenance of its properties is important to keep normal tissue architecture and function. Based on experimental model of SSc discovered in our laboratory, in which over expression of abnormal COLV was a prominent feature, we assumed that this abnormality could be also present in SSc patients.
Methods:
skin biopsies of 18 patients (5 at early and 13 at late disease stage) and 10 healthy controls were studied for histological, molecular and biochemical profiles of COLV. Assessment of skin thickness was performed using the Modified Rodnan Skin Score (MRSS) and disease activity was calculated by Valentini Disease Activity Index. Quantification of COLV was obtained by histomorphometry done in dermis and quantitative RT-PCR of dermal fibroblasts culture. Additionally, fibroblasts culture supernatant immunoblotting and tridimentional reconstruction of COLV were performed.
Results:
The COLV content in the dermis was higher in early-SSc (44.60 + 10.63%) when compared to controls (24.61 + 5.61%, p<0.01) and late-SSc (33.30 + 4.38%, p<0.01) A positive correlation between COLV and MRSS (r=0.42, p=0.04) as well as disease activity (r=0.45, p=0.03) was observed. The gene expression of COLV alpha 1 and COLV alpha 2 was increased in SSc patients when compared to controls (2.2-fold, p=0.02 and 5.9-fold, p<0.01; respectively). Higher expression of both chains were observed in SSc dermal fibroblasts culture supernatant. Tridimensional reconstruction of collagen fibers confirmed expression of thickened and distorted COLV in SSc patients, different from thin fibrils observed in healthy controls.
Conclusion:
Increased synthesis of structurally abnormal COLV is observed in dermis of SSc patients. Since this collagen participates of heterotypic fiber assembly, morphological changes of COLV could explain histoarchitectural disarrangement and skin thickening, mainly at early SSc stage. The positive correlation between dermal COLV expression and disease activity, suggests that besides structural role and loss of regulatory function, COLV may be involved in additional pathophysiological mechanisms.
To cite this abstract, please use the following information:
Martin, Patricia, Teodoro, Walcy R., Velosa, Ana Paula P., de Morais, Jymenez, Carrasco, Solange, Braga, Francine F. R., et al; Abnormal Morphology and Excessive Synthesis of Collagen V Affects Skin Thickness and Disease Activity in Systemic Sclerosis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1486
DOI:
