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Granuloma annulare skin profile shows activation of T-helper cell type 1, T-helper cell type 2, and Janus kinase pathways - 19/06/20

Doi : 10.1016/j.jaad.2019.12.028 
Michelle S. Min, MD, MSci a, Jianni Wu, BS a, b, Helen He, BS a, Juan Luis Sanz-Cabanillas, MD c, Ester Del Duca, MD a, d, Ning Zhang, MD a, Yael Renert-Yuval, MD e, Ana B. Pavel, PhD a, Mark Lebwohl, MD a, Emma Guttman-Yassky, MD, PhD a, e,
a Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 
b College of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York 
c Department of Dermatology, Reina Sofia University Hospital, Córdoba, Spain 
d Department of Dermatology, University of Rome Tor Vergata, Rome, Italy 
e Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 

Correspondence to: Emma Guttman-Yassky, MD, PhD, Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, 5 E 98th St, New York, NY 10029.Department of Dermatology and Laboratory of Inflammatory Skin DiseasesIcahn School of Medicine at Mount Sinai5 E 98th StNew YorkNY10029



Granuloma annulare (GA) is an inflammatory skin disorder. Localized GA is often self-resolving, but generalized GA is often recalcitrant to treatments. There are no targeted treatments for GA, largely due to lack of mechanistic understanding. Recently, tumor necrosis factor antagonism showed promise in GA, suggesting an underlying immune pathogenesis.


To elucidate the immune pathogenesis and identify potential therapeutic targets for GA.


Lesional and nonlesional skin biopsy samples were obtained from patients with GA and evaluated for a large array of inflammatory markers compared with inflammatory markers from normal skin of healthy individuals.


We found differential expression of many inflammatory genes compared with normal skin. These genes were associated with T-helper (Th) cell type 1/innate immunity (tumor necrosis factor-α, interleukin [IL]-1β, IL-12/23p40, signal transducer and activator of transcription 1, chemokine [C-X-C motif] ligand 9/10), Janus kinase signaling, and Th2 (IL-4, IL-31, chemokine (C-C motif) ligands 17 and 18; P < .05). Unexpectedly, IL-4 showed significant upregulation in GA lesional skin vs control skin (15,600-fold change).


Limited sample size.


Our findings shed light on the inflammatory pathways of GA, supporting the notion that immune mechanisms could be driving disease, as suggested by the promising data of tumor necrosis factor-α inhibitors in GA. The significant Janus kinase and particularly Th2 signaling in GA advocates for the investigation of specific Janus kinase- and Th2- targeted drug therapy.

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Graphical abstract

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Key words : dermatology, granuloma annulare, immunology, pathogenesis

Abbreviations used : AD, CAMP, CCL, CXCL, FCH, GA, IFN-γ, IL, JAK, KRT16, MMP, mRNA, OSM, RT-PCR, STAT, SYK, Th, TNF-α, TYK


 Authors Min and Wu contributed equally to this article as cofirst authors.
 Funding sources: None.
 Conflicts of interest: Drs Zhang and Pavel are employees of Mount Sinai. Dr Lebwohl is an employee of Mount Sinai, which receives research funds from Amgen Inc, Anacor Pharmaceuticals, Inc, Boehringer Ingelheim, Celgene Corporation, Eli Lilly & Co, Janssen Biotech, Kadmon Corporation, LLC, LEO Pharma, MedImmune, LLC, Novartis AG, Pfizer Inc, Sun Pharmaceutical Industries Inc, and Valeant Pharmaceuticals North America LLC. Dr Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from AbbVie, Celgene, Eli Lilly, Janssen, MedImmune, AstraZeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB, and is also a consultant for Sanofi, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, LEO Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. Authors Min, Wu, He, Sanz-Cabanillas, Del Duca, and Renert-Yuval have no conflicts of interest to disclose.
 Reprints not available from the authors.
 IRB approval status: Reviewed and approved by the Mount Sinai Institutional Review Board (approval HS #14-00436.)

© 2019  American Academy of Dermatology, Inc.. Publié par Elsevier Masson SAS. Tous droits réservés.
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