Molecular profiling and gene expression analysis in cutaneous sarcoidosis: The role of interleukin-12, interleukin-23, and the T-helper 17 pathway - 13/05/12
, Richard M. Marchell, MD a, MaryAnn Mascelli, PhD b, Alexa Piantone, PharmD b, Elliot S. Barnathan, MD b, Kevin J. Petty, MD b, Dion Chen, PhD b, Hongtao Fan, PhD b, Heidi Grund, RN a, Keying Ma, PhD b, Frédéric Baribaud, PhD b, Carrie Brodmerkel, PhD b
Reprint requests: Marc A. Judson, MD, Division of Pulmonary and Critical Care Medicine, AMC Pulmonary and Critical Care Medicine, 47 New Scotland Ave, MC 91, Physicians Pavilion, Fourth Floor, Albany, NY 12208.Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : interferon-gamma, interleukin-12, interleukin-21, interleukin-23, lesional sarcoidosis, nonlesional sarcoidosis
Abbreviations used : cDNA, CS, CXCL, FDR, IFN, IL, LS, NLS, PCR, RRT, STAT, TGF, Th, TNF
Plan
| Dr Judson is currently affiliated with Division of Pulmonary and Critical Care Medicine, AMC Pulmonary and Critical Care Medicine, Albany, New York. |
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| Funded by Centocor Research and Development, a Division of Johnson & Johnson Pharmaceutical Research & Development, LLC. |
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| Disclosure: Dr Mascelli is a salaried consultant and Drs Piantone, Barnathan, Petty, Chen, Fan, Ma, Baribaud, and Brodmerkel are salaried employees of Centocor Research and Development, a subsidiary of Johnson & Johnson. Drs Barnathan, Petty, Baribaud, and Brodmerkel own stock and stock options in Johnson & Johnson. Drs Judson and Marchell, and Ms Grund have no conflicts of interest to declare. |
Vol 66 - N° 6
P. 901 - juin 2012 Retour au numéro
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