Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea

Jack C. O'Brien, Yevgeniya Byekova Rainwater, Neeta Malviya, Nika Cyrus, Lorenz Auer-Hackenberg, Linda S. Hynan, Gregory A. Hosler, Heidi T. Jacobe

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

IFN-related pathways have not been studied in morphea, and biomarkers are needed. We sought to characterize morphea serum cytokine imbalance and IFN-related gene expression in blood and skin to address this gap by performing a case-control study of 87 participants with morphea and 26 healthy control subjects. We used multiplexed immunoassays to determine serum cytokine concentrations, performed transcriptional profiling of whole blood and lesional morphea skin, and used double-staining immunohistochemistry to determine the cutaneous cellular source of CXCL9. We found that CXCL9 was present at increased concentrations in morphea serum (P < 0.0001), as were other T helper type 1 cytokines. CXCL9 serum concentration correlated with the modified Localized Scleroderma Skin Severity Index (r = 0.44, P = 0.0001), a validated measure of disease activity. CXCL9 gene expression was also increased in inflammatory lesional morphea skin (fold change = 30.6, P = 0.006), and preliminary transcriptional profiling showed little evidence for IFN signature in whole blood. Double-staining immunohistochemistry showed CXCL9 co-localized with CD68+ dermal macrophages. In summary, inflammatory morphea is characterized by T helper type 1 cytokine imbalance in serum, particularly CXCL9, which is associated with disease activity. CXCL9 expression in lesional macrophages implicates the skin as the source of circulating cytokines. CXCL9 is a promising biomarker of disease activity in morphea.

Original languageEnglish (US)
Pages (from-to)1663-1670
Number of pages8
JournalJournal of Investigative Dermatology
Volume137
Issue number8
DOIs
StatePublished - Aug 1 2017

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Localized Scleroderma
Biomarkers
Skin
Cytokines
Blood
Macrophages
Gene expression
Serum
Immunohistochemistry
Staining and Labeling
Gene Expression
Immunoassay
Case-Control Studies
Healthy Volunteers

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea. / O'Brien, Jack C.; Rainwater, Yevgeniya Byekova; Malviya, Neeta; Cyrus, Nika; Auer-Hackenberg, Lorenz; Hynan, Linda S.; Hosler, Gregory A.; Jacobe, Heidi T.

In: Journal of Investigative Dermatology, Vol. 137, No. 8, 01.08.2017, p. 1663-1670.

Research output: Contribution to journalArticle

O'Brien, Jack C. ; Rainwater, Yevgeniya Byekova ; Malviya, Neeta ; Cyrus, Nika ; Auer-Hackenberg, Lorenz ; Hynan, Linda S. ; Hosler, Gregory A. ; Jacobe, Heidi T. / Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea. In: Journal of Investigative Dermatology. 2017 ; Vol. 137, No. 8. pp. 1663-1670.
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