Session Information
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose: The extent of skin disease in patients with systemic sclerosis is typically measured through physical examination of patients at 17 sites and involvement is quantified on a scale from uninvolved to severe involvement (0 to 3). The total of all 17 sites scores is defined as the Modified Rodnan Skin Score (MRSS). We have shown previously that gene expression of skin biopsies taken from the mid-forearm correlates well with overall skin disease as assessed by the MRSS. However, it remained unclear whether the success of such an approach represented a particularly accurate, molecular, quantification of local skin disease or a manifestation of altered gene expression known to occur in all the skin of systemic sclerosis patients, both lesional and non-lesional.
Methods: Skin biopsies (n=42) from the forearms of patients with diffuse cutaneous SSc (dcSSc) and healthy donors (n=5) were assessed for expression of genes we have previously identified as elevated in SSc skin. The results were assessed for difference (one-way ANOVA) in gene expression (p≤0.05) with forearm skin score (0 to 3) and correlation with forearm skin score (Pearson’s).
Results: Expression of all genes examined form patients showing a local skin score of 1 or greater were different from healthy control. Several inflammatory, TGFβ, and WNT regulated genes (CCL2, IL13RA1, COMP, THBS-1, ADAM12, and WIF1) showed a significant correlation with the local forearm score (1 or greater). Other inflammatory and macrophage related genes (IFI44, CD163, SIGLEC1, CD14) showed no significant correlation between the level of gene expression and the local skin score.
Conclusion: The different relationships between local gene expression, and local versus systemic assessment of the skin score (MRSS) suggest a hierarchy of molecular events. Gene expression correlating most highly with the local skin score may represent molecular events closest to clinical manifestations. Altered gene expression that does not correlate with the skin score may represent more molecular events earlier in the pathogenic cascade, or alternatively epiphenomena without direct roles in pathogenesis. These results have particular implications for biomarker selection in clinical trials of drugs delivered by local topical application.
Disclosure:
L. Rice,
None;
G. Stifano,
None;
J. Ziemek,
None;
R. Lafyatis,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/assessment-of-mrna-gene-expression-based-on-forearm-skin-score-in-systemic-sclerosis-patients/