Inclusion body myositis

Laser microdissection reveals differential Up-regulation of IFN-γ signaling cascade in attacked versus nonattacked myofibers

Jana Ivanidze, Reinhard Hoffmann, Hanns Lochmller, Andrew G Engel, Reinhard Hohlfeld, Klaus Dornmair

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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. HLA-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) γ receptor (IFNGR2) and several IFN-γinduced 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-γ 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.

Original languageEnglish (US)
Pages (from-to)1347-1359
Number of pages13
JournalAmerican Journal of Pathology
Volume179
Issue number3
DOIs
StatePublished - Sep 2011

Fingerprint

Inclusion Body Myositis
Microdissection
Interferons
Lasers
Up-Regulation
HLA Antigens
T-Lymphocytes
Interferon Receptors
Inflammation
Muscles
Antigen Presentation
Confocal Microscopy
Macrophages

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Inclusion body myositis : Laser microdissection reveals differential Up-regulation of IFN-γ signaling cascade in attacked versus nonattacked myofibers. / Ivanidze, Jana; Hoffmann, Reinhard; Lochmller, Hanns; Engel, Andrew G; Hohlfeld, Reinhard; Dornmair, Klaus.

In: American Journal of Pathology, Vol. 179, No. 3, 09.2011, p. 1347-1359.

Research output: Contribution to journalArticle

Ivanidze, Jana ; Hoffmann, Reinhard ; Lochmller, Hanns ; Engel, Andrew G ; Hohlfeld, Reinhard ; Dornmair, Klaus. / Inclusion body myositis : Laser microdissection reveals differential Up-regulation of IFN-γ signaling cascade in attacked versus nonattacked myofibers. In: American Journal of Pathology. 2011 ; Vol. 179, No. 3. pp. 1347-1359.
@article{6f36ec504d67427ab81cfb72815393e9,
title = "Inclusion body myositis: Laser microdissection reveals differential Up-regulation of IFN-γ signaling cascade in attacked versus nonattacked myofibers",
abstract = "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. HLA-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) γ receptor (IFNGR2) and several IFN-γinduced 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-γ 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.",
author = "Jana Ivanidze and Reinhard Hoffmann and Hanns Lochmller and Engel, {Andrew G} and Reinhard Hohlfeld and Klaus Dornmair",
year = "2011",
month = "9",
doi = "10.1016/j.ajpath.2011.05.055",
language = "English (US)",
volume = "179",
pages = "1347--1359",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Inclusion body myositis

T2 - Laser microdissection reveals differential Up-regulation of IFN-γ signaling cascade in attacked versus nonattacked myofibers

AU - Ivanidze, Jana

AU - Hoffmann, Reinhard

AU - Lochmller, Hanns

AU - Engel, Andrew G

AU - Hohlfeld, Reinhard

AU - Dornmair, Klaus

PY - 2011/9

Y1 - 2011/9

N2 - 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. HLA-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) γ receptor (IFNGR2) and several IFN-γinduced 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-γ 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.

AB - 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. HLA-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) γ receptor (IFNGR2) and several IFN-γinduced 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-γ 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.

UR - http://www.scopus.com/inward/record.url?scp=80052854800&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052854800&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2011.05.055

DO - 10.1016/j.ajpath.2011.05.055

M3 - Article

VL - 179

SP - 1347

EP - 1359

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -