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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. 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)