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  Inclusion Body Myositis Laser Microdissection Reveals Differential Up-Regulation of IFN-gamma Signaling Cascade in Attacked versus Nonattacked Myofibers

Ivanidze, J., Hoffmann, R., Lochmueller, H., Engel, A. G., Hohlfeld, R., & Dornmair, K. (2011). Inclusion Body Myositis Laser Microdissection Reveals Differential Up-Regulation of IFN-gamma Signaling Cascade in Attacked versus Nonattacked Myofibers. AMERICAN JOURNAL OF PATHOLOGY, 179(3), 1347-1359. doi:10.1016/j.ajpath.2011.05.055.

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Ivanidze, Jana1, Autor           
Hoffmann, Reinhard2, Autor
Lochmueller, Hanns2, Autor
Engel, Andrew G.2, Autor
Hohlfeld, Reinhard1, Autor           
Dornmair, Klaus1, Autor           
Affiliations:
1Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              
2External Organizations, ou_persistent22              

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Schlagwörter: IDIOPATHIC INFLAMMATORY MYOPATHIES; MHC CLASS-I; MONOCLONAL-ANTIBODY ANALYSIS; CELL-RECEPTOR EXPRESSION; SKELETAL-MUSCLE LEADS; CYTOTOXIC T-CELLS; COMPLEX CLASS-I; AUTOIMMUNE MYOSITIS; MONONUCLEAR-CELLS; KAPPA-BPathology;
 Zusammenfassung: Sporadic inclusion body myositis (IBM) is a muscle disease with two separate pathogenic components, degeneration and inflammation. Typically, nonnecrotic myofibers are focally surrounded and invaded by CD8(+) T cells and macrophages. Both attacked and nonattacked myofibers express high levels of human leukocyte antigen class I (HLA-I) molecules, a prerequisite for antigen presentation to CD8(+) T cells. However, only a subgroup of HLA-I+ myofibers is attacked by immune cells. By using IHC, we classified myofibers from five patients with sporadic IBM as attacked (A(IBM)) or nonattacked (N-IBM) and isolated the intracellular contents of myofibers separately by laser microdissection. For comparison, we isolated myofibers from control persons (H-CTRL). The samples were analyzed by microarray hybridization and quantitative PCR. HIA-I up-regulation was observed in A(IBM) and N-IBM, whereas H-CTRL were negative for HLA-I. In contrast, the inducible chain of the interferon (IFN) gamma receptor (IFNGR2) and several IFN-gamma-induced genes were up-regulated in A(IBM) compared with N-IBM and H-CTRL fibers. Confocal microscopy confirmed segmental IFNGR2 up-regulation on the membranes of A(IBM), which positively correlated with the number of adjacent CD8(+) T cells. Thus, the differential up-regulation of the IFN-gamma signaling cascade observed in the attacked fibers is related to local inflammation, whereas the ubiquitous HLA-I expression on IBM muscle fibers does not require IFNGR expression. (Am J Pathol 2011, 179:1347-1359; DOI:10.1016/j.ajpath.2011.05.055)

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Sprache(n): eng - English
 Datum: 2011-09
 Publikationsstatus: Erschienen
 Seiten: 13
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000298307300029
DOI: 10.1016/j.ajpath.2011.05.055
 Art des Abschluß: -

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Titel: AMERICAN JOURNAL OF PATHOLOGY
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA : ELSEVIER SCIENCE INC
Seiten: - Band / Heft: 179 (3) Artikelnummer: - Start- / Endseite: 1347 - 1359 Identifikator: ISSN: 0002-9440