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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Baer, Alan N. Rosen, Antony Kapsogeorgou, Efstathia K. Tzioufas, Athanasios G. Casciola-rosen, Livia Berger, Alan E. Hall, John C. Cheadle, Chris |
| Description | Author Affiliation: Hall JC ( Division of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.); |
| Abstract | Elucidating the molecular pathways active in pathologic tissues has important implications for defining disease subsets, selecting therapy, and monitoring disease activity. The development of therapeutics directed at IFN- or IFN-γ makes the discovery of probes that report precisely on the activity of different IFN pathways a high priority. We show that, although type I and II IFNs induce the expression of a largely overlapping group of molecules, precise probes of IFN-γ activity can be defined. Used in combination, these probes show prominent IFN-γ effects in Sjögren syndrome (SS) tissues. In contrast, dermatomyositis muscle shows a dominant type I IFN pattern. Interestingly, heterogeneity of IFN signatures exists in patients with SS, with some patients demonstrating a predominant type I pattern. The biochemical patterns largely distinguish the target tissues in patients with SS from those with dermatomyositis and provide a relative weighting of the effects of distinct IFN pathways in specific biopsies. In SS, type I and II IFN effects are localized to the same epithelial cells, surrounded by inflammatory cells expressing IFN-γ-induced proteins, suggesting reinforcing interactions. Precise probes of the different IFN pathways active in tissues of complex rheumatic diseases will be critical to classify disease, elucidate pathogenesis, and select therapy. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 43 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Interferon-gamma Physiology Rheumatic Diseases Physiopathology Epithelial Cells Metabolism Gene Expression Regulation Salivary Glands Cytology Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Validation Studies Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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