PMID- 21855683
OWN - NLM
STAT- MEDLINE
DCOM- 20111209
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 179
IP  - 3
DP  - 2011 Sep
TI  - Inclusion body myositis: laser microdissection reveals differential up-regulation 
      of IFN-gamma signaling cascade in attacked versus nonattacked myofibers.
PG  - 1347-59
LID - 10.1016/j.ajpath.2011.05.055 [doi]
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) 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.
CI  - Copyright (c) 2011 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Ivanidze, Jana
AU  - Ivanidze J
AD  - Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Munich, 
      Germany.
FAU - Hoffmann, Reinhard
AU  - Hoffmann R
FAU - Lochmuller, Hanns
AU  - Lochmuller H
FAU - Engel, Andrew G
AU  - Engel AG
FAU - Hohlfeld, Reinhard
AU  - Hohlfeld R
FAU - Dornmair, Klaus
AU  - Dornmair K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (HLA Antigens)
RN  - 0 (IFNGR2 protein, human)
RN  - 0 (Receptors, Interferon)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Aged
MH  - Case-Control Studies
MH  - Female
MH  - HLA Antigens/metabolism
MH  - Humans
MH  - Interferon-gamma/*metabolism
MH  - Laser Therapy
MH  - Male
MH  - Microdissection
MH  - Middle Aged
MH  - Muscle Fibers, Skeletal/*metabolism/pathology
MH  - Muscle, Skeletal/pathology/surgery
MH  - Myositis, Inclusion Body/*metabolism/pathology
MH  - Receptors, Interferon/metabolism
MH  - Signal Transduction/physiology
MH  - *Up-Regulation
PMC - PMC3157228
EDAT- 2011/08/23 06:00
MHDA- 2011/12/14 06:00
PMCR- 2012/09/01
CRDT- 2011/08/23 06:00
PHST- 2011/02/10 00:00 [received]
PHST- 2011/05/25 00:00 [revised]
PHST- 2011/05/31 00:00 [accepted]
PHST- 2011/08/23 06:00 [entrez]
PHST- 2011/08/23 06:00 [pubmed]
PHST- 2011/12/14 06:00 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
AID - S0002-9440(11)00555-4 [pii]
AID - 10.1016/j.ajpath.2011.05.055 [doi]
PST - ppublish
SO  - Am J Pathol. 2011 Sep;179(3):1347-59. doi: 10.1016/j.ajpath.2011.05.055.