Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea Jack C. O’Brien, Yevgeniya Byekova Rainwater, Neeta.

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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 Journal of Investigative Dermatology Volume 137, Issue 8, Pages 1663-1670 (August 2017) DOI: 10.1016/j.jid.2017.04.008 Copyright © 2017 The Authors Terms and Conditions

Figure 1 CXCL9 and CXCL10 are elevated in morphea serum. (a) CXCL9 and CXCL10 are present at increased concentrations compared with control samples. (b, c) CXCL9 is increased in active morphea, decreases in inactive disease, and correlates with disease activity, but CXCL10 does not. (d) Both correlate with measures of disease damage. (e) CXCL9 concentrations correlate with CXCL10 concentrations. LoSDI, Localized Scleroderma Skin Damage Index; mLoSSI, modified Localized Scleroderma Skin Severity Index. Journal of Investigative Dermatology 2017 137, 1663-1670DOI: (10.1016/j.jid.2017.04.008) Copyright © 2017 The Authors Terms and Conditions

Figure 2 CXCL9 is increased in inflammatory morphea skin. (a) CXCL9 mRNA expression is increased in lesional skin compared with site-matched unaffected skin. (b, c) CXCL9 is present in dermal interstitial infiltrates and stains dendritic-appearing cells. Arrows indicate typical perinuclear cap staining pattern of CXCL9. Scale bar in b = 100 μm; scale bar in c = 25 μm. Journal of Investigative Dermatology 2017 137, 1663-1670DOI: (10.1016/j.jid.2017.04.008) Copyright © 2017 The Authors Terms and Conditions

Figure 3 Morphea skin, immunohistochemistry. (a) CD3- and (b) CD4-positive cells make up most of the inflammatory infiltrate. (c) CD8+ lymphocytes and (d) CD68+ macrophages were present less frequently. Scale bar = 50 μm. Journal of Investigative Dermatology 2017 137, 1663-1670DOI: (10.1016/j.jid.2017.04.008) Copyright © 2017 The Authors Terms and Conditions

Figure 4 Morphea skin, double-staining immunohistochemistry. (a) The inflammatory cell infiltrate was enriched with CXCR3+ cells that stained similar cells as CD4 (brown) and CXCR3 (purple) double immunostain. (b) CXCL9 co-localized with CD68. CXCL9 (purple) and CD68 (brown) double immunostain; arrows indicate double-staining. (c) CXCL9+ cells were in close proximity to CXCR3+ lymphocytes. CXCL9 (purple, arrow) and CXCR3 (brown, arrow). Scale bar = 25 μm. Journal of Investigative Dermatology 2017 137, 1663-1670DOI: (10.1016/j.jid.2017.04.008) Copyright © 2017 The Authors Terms and Conditions