Drs. Liu and Ramot contributed equally to this work.
Mutations in proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity
Version of Record online: 28 FEB 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 3, pages 895–907, March 2012
How to Cite
Liu, Y., Ramot, Y., Torrelo, A., Paller, A. S., Si, N., Babay, S., Kim, P. W., Sheikh, A., Lee, C.-C. R., Chen, Y., Vera, A., Zhang, X., Goldbach-Mansky, R. and Zlotogorski, A. (2012), Mutations in proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis & Rheumatism, 64: 895–907. doi: 10.1002/art.33368
- Issue online: 28 FEB 2012
- Version of Record online: 28 FEB 2012
- Accepted manuscript online: 27 SEP 2011 10:22AM EST
- Manuscript Accepted: 20 SEP 2011
- Manuscript Received: 9 JUN 2011
- Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH
- Authority for Research and Development, Hebrew University of Jerusalem
- Hadassah Medical Center Young Clinician Award
Additional Supporting Information may be found in the online version of this article.
|ART_33368_sm_SupplTable1.doc||32K||Supplementary Table 1|
|ART_33368_sm_SupplTable2.pdf||72K||Supplementary Table 2|
|ART_33368_sm_SupplFig1.tif||28K||Supplementary Figure 1. Model of dysregulated IFN pathways in CANDLE. Mutant i-proteasome induced IFN signaling abnormality is depicted in this tentative model. In response to a trigger such as infections, IFNs are produced which upregulate the expression of the i-proteasome to process the accumulating polyubiquitinated proteins. Defects in i-proteasomes caused by PSMB8 mutations results in increase of polyubiquitinated proteins and cell stress, which then trigger more IFN production, leading to a vicious cycle.|
|ART_33368_sm_SupplFig2.tif||1483K||Supplementary Figure 2. IFN signature under treatment with biologics in one CANDLE patient. Various treatments with biologics [TNF-alpha inhibition (adalimumab), IL-6 inhibition (tocilizumab), inhibition of the CD28/CD86 interaction (abatacept), or a calcineurin inhibitor (tacrolimus)] led to persistence of the interferon signature on microarray analysis. In red are upregulated genes compared to healthy age matched children.|
Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.