BACKGROUND: Cutaneous sarcoidosis (CS) skin provides relatively noninvasive access to granulomatous sarcoidosis tissue. OBJECTIVE: We sought to explore the role of the T-helper (Th)1 and Th17 pathways in sarcoidosis. METHODS: We used molecular profiling and gene expression analysis to analyze the Th1 and Th17 pathways and other immune-mediated pathways in CS. Molecular profiles were obtained from sarcoidosis skin lesions (lesional skin [LS]), unaffected skin from patients with CS (non-LS), and the skin of healthy control subjects. Whole blood was collected to compare the molecular profile of sarcoidosis skin lesions and whole blood. RESULTS: Twenty participants were enrolled: 15 with active CS and 5 healthy volunteers. Microarray analyses comparing non-LS and healthy volunteer skin with LS showed several thousand genes differentially expressed (≥2-fold change false discovery rate, P < .01). Targeted selections of genes associated with Th1 and Th17 phenotypes showed a strong Th1 profile of sarcoidosis and expression of interleukin (IL)-23 and IL-23R with limited expression of other Th17 pathway genes. IL-21 and signal transducer and activator of transcription 3 (STAT3) were also dysregulated in skin and whole blood, providing additional evidence for involvement of the IL-12 pathway and potential activation of the Th17 pathway. LIMITATIONS: Measurements were made at a single point in time and may not identify mechanisms that may be identified in patients followed up longitudinally. CONCLUSION: These findings provide novel insight into the dysregulated pathways that may be involved in the pathogenesis of sarcoidosis.
BACKGROUND:Cutaneous sarcoidosis (CS) skin provides relatively noninvasive access to granulomatous sarcoidosis tissue. OBJECTIVE: We sought to explore the role of the T-helper (Th)1 and Th17 pathways in sarcoidosis. METHODS: We used molecular profiling and gene expression analysis to analyze the Th1 and Th17 pathways and other immune-mediated pathways in CS. Molecular profiles were obtained from sarcoidosis skin lesions (lesional skin [LS]), unaffected skin from patients with CS (non-LS), and the skin of healthy control subjects. Whole blood was collected to compare the molecular profile of sarcoidosis skin lesions and whole blood. RESULTS: Twenty participants were enrolled: 15 with active CS and 5 healthy volunteers. Microarray analyses comparing non-LS and healthy volunteer skin with LS showed several thousand genes differentially expressed (≥2-fold change false discovery rate, P < .01). Targeted selections of genes associated with Th1 and Th17 phenotypes showed a strong Th1 profile of sarcoidosis and expression of interleukin (IL)-23 and IL-23R with limited expression of other Th17 pathway genes. IL-21 and signal transducer and activator of transcription 3 (STAT3) were also dysregulated in skin and whole blood, providing additional evidence for involvement of the IL-12 pathway and potential activation of the Th17 pathway. LIMITATIONS: Measurements were made at a single point in time and may not identify mechanisms that may be identified in patients followed up longitudinally. CONCLUSION: These findings provide novel insight into the dysregulated pathways that may be involved in the pathogenesis of sarcoidosis.
Authors: Natalia V Rivera; Marcus Ronninger; Klementy Shchetynsky; Andre Franke; Markus M Nöthen; Joachim Müller-Quernheim; Stefan Schreiber; Indra Adrianto; Bekir Karakaya; Coline H M van Moorsel; Zdenka Navratilova; Vitezslav Kolek; Benjamin A Rybicki; Michael C Iannuzzi; Martin Petrek; Jan C Grutters; Courtney Montgomery; Annegret Fischer; Anders Eklund; Leonid Padyukov; Johan Grunewald Journal: Am J Respir Crit Care Med Date: 2016-05-01 Impact factor: 21.405
Authors: James T Rosenbaum; Dongseok Choi; David J Wilson; Hans E Grossniklaus; Christina A Harrington; Cailin H Sibley; Roger A Dailey; John D Ng; Eric A Steele; Craig N Czyz; Jill A Foster; David Tse; Chris Alabiad; Sander Dubovy; Prashant Parekh; Gerald J Harris; Michael Kazim; Payal Patel; Valerie White; Peter Dolman; Bobby S Korn; Don Kikkawa; Deepak P Edward; Hind Alkatan; Hailah Al-Hussain; R Patrick Yeatts; Dinesh Selva; Patrick Stauffer; Stephen R Planck Journal: JAMA Ophthalmol Date: 2015-07 Impact factor: 7.389