@article{3057088,
    title = "Precise probes of type II interferon activity define the origin of interferon signatures in target tissues in rheumatic diseases",
    author = "Hall, J.C. and Casciola-Rosen, L. and Berger, A.E. and Kapsogeorgou, E.K. and Cheadle, C. and Tzioufas, A.G. and Baer, A.N. and Rosen, A.",
    journal = "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA",
    year = "2012",
    volume = "109",
    number = "43",
    pages = "17609-17614",
    doi = "10.1073/pnas.1209724109",
    keywords = "alpha interferon;  gamma interferon;  messenger RNA, article;  biological activity;  controlled study;  dermatomyositis;  epithelium cell;  human;  human cell;  human tissue;  immunoblotting;  inflammatory cell;  microarray analysis;  molecular probe;  muscle biopsy;  pathogenesis;  priority journal;  protein expression;  protein interaction;  protein localization;  salivary gland biopsy;  Sjoegren syndrome, Epithelial Cells;  Gene Expression Regulation;  Humans;  Interferon-gamma;  Rheumatic Diseases;  Salivary Glands",
    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-α 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."
}