| Description |
Morphea is an inflammatory disorder of the skin and soft tissue characterized by fibrosis that has been likened to systemic sclerosis (SSc). We sought to capture the molecular heterogeneity of morphea by examining lesional skin gene expression and blood biomarkers, and compare the gene expression profiles with those from SSc lesional and site matched non lesional skin, as well as sera obtained from adult patients with untreated morphea. We found the morphea transcriptome is dominated by IFNg-mediated Th1 immune dysregulation, with relative paucity of pathways associated with fibrosis. These results were mirrored when morphea gene expression profiles were compared with SSc. Interestingly, expression profiles of morphea skin samples clustered with the SSc inflammatory subset and distinct from the SSc fibro-proliferative subset. Unaffected morphea skin also differed from unaffected SSc skin in that it did not exhibit pathological gene expression signatures. Examination of downstream IFNg-mediated chemokines, CXCL9 and CXCL10, revealed increased transcription in the skin but not in sera. While elevated serum CXCL9 proteins quantified by ELISA were associated with active disease and widespread cutaneous disease. Taken together, these results indicate that inflammatory and sclerotic morphea is a skin directed process characterized by Th1 immune mediated dysregulation, which contrasts with fibrotic signatures and systemic transcriptional changes associated with SSc. The association of circulating CXCL9 concentration with clinical activity and burden of skin disease supports its potential as a readily accessible biomarker.
Overall design: We profiled the transcriptome of inflammatory (n=10) and sclerotic (n=15) lesional morphea versus site-matched unaffected skin (n=11) using microarray analysis. |
