- 作者：Marc A. Judson ; MD<sup>asup><sup> ; sup><sup>judsonm@mail.amc.edusup> ; Richard M. Marchell ; MD<sup>asup> ; MaryAnn Mascelli ; PhD<sup>bsup> ; Alexa Piantone ; PharmD<sup>bsup> ; Elliot S. Barnathan ; MD<sup>bsup> ; Kevin J. Petty ; MD<sup>bsup> ; Dion Chen ; PhD<sup>bsup> ; Hongtao Fan ; PhD<sup>bsup> ; Heidi Grund ; RN<sup>asup> ; Keying Ma ; PhD<sup>bsup> ; Fré ; dé ; ric Baribaud ; PhD<sup>bsup> ; Carrie Brodmerkel ; PhD<sup>bsup>
- 关键词：interferon-gamma ; interleukin-12 ; interleukin-21 ; interleukin-23 ; lesional sarcoidosis ; nonlesional sarcoidosis
- 刊名：Journal of the American Academy of Dermatology
- 出版年：2012
- 出版时间：June, 2012
- 年：2012
- 卷：66
- 期：6
- 页码：901-910.e2
- 全文大小：638 K
ss=""h4"">Background
Cutaneous sarcoidosis (CS) skin provides relatively noninvasive access to granulomatous sarcoidosis tissue.ss=""h4"">Objective
We sought to explore the role of the T-helper (Th)1 and Th17 pathways in sarcoidosis.
ss=""h4"">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.
ss=""h4"">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 (?-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.
ss=""h4"">Limitations
Measurements were made at a single point in time and may not identify mechanisms that may be identified in patients followed up longitudinally.
ss=""h4"">Conclusion
These findings provide novel insight into the dysregulated pathways that may be involved in the pathogenesis of sarcoidosis.