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

Michelle S. Min, Jianni Wu, Helen He, Juan Luis Sanz-Cabanillas, Ester Del Duca, Ning Zhang, Yael Renert-Yuval, Ana B. Pavel, Mark Lebwohl, Emma Guttman-Yassky

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Background: 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. Objective: To elucidate the immune pathogenesis and identify potential therapeutic targets for GA. Methods: 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. Results: 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). Limitations: Limited sample size. Conclusions: 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.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalJournal of the American Academy of Dermatology
Issue number1
StatePublished - Jul 2020


  • dermatology
  • granuloma annulare
  • immunology
  • pathogenesis


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