Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Necrotizing auto-immune myopathies (NAM) are a group of acquired idiopathic inflammatory myopathies characterized by severe muscle weakness and no or mild extra-muscular involvement. Definition of NAM is based on morphological features including fiber necrosis with no or few inflammation. Anti-SRP and anti-HMGCR auto-antibodies are specifically associated with NAM. However, to date data concerning histological features of anti-SRP or anti-HMGCR auto-antibody positive NAM patients (SRP+ or HMGCR+ NAM) are rare and mechanisms involved in fiber necrosis are totally unknown. We aim to describe the histological pattern of the skeletal muscle of a large series of SRP+ or HMGCR+NAM patients and to analyze mechanisms involved in muscle necrosis.
Methods:
Fiber necrosis was detected on combined dystrophin stain and eosin counterstaining. Fiber necrosis were manually counted and normal fibers were automatically counted using imageJ software on digitally completely scanned slides. For immunohistochemical analysis, cell density was measured. Results are compare to a myositis group of anti-Jo-1 auto-antibody positive patients. A panel of immune mediators was tested by quantitative PCR in muscle biopsies (expressed as normalized fold change relative to normal muscle).
Results:
The percentage of fiber necrosis is higher (3.2±2.5%) in SRP+ NAM patients (n=22) compared to 1.6±1.5% in HMGCR+ NAM patients (n=19) (p=0.02) and 1.6±2.5% in Jo-1+ patients (n=17) (p=0.007). Amount of necrosis is not different in HMGCR+ NAM patients vs. Jo1+ patients but 80.7±6.7% of necrosis occurs in perifasciuclar region in Jo-1+ patients (25.3±2.8% in NAM; p<0.001). T cells and CD8+ T cells densities are higher in Jo-1+ patients (33.2±7.9 cells/mm2 and 22.3±24.6 cells/mm2) compared to NAM patients (10.2±2.3 and 4.1±6.0 cells/mm2; p=0.001) but 17.7% of NAM patients harbored significant T cells infiltrates (>20 cells/mm2). A diffuse MHC-I expression was observed in 22.7% of NAM patient vs. 87% in Jo1+ patients (p<0.001). In NAM patients T cells, CD8+ T cell densities are correlated with amount of necrosis (r=0.5 and r=0.4; p<0.01) and an up-regulation of IFN-γ gene expression is observed in NAM patients (SRP+ (n=7) and HMGCR+(n=7)).
On the other hand, a Th-2 immune polarization is observed in SRP+ (n=7) and HMGCR+ (n=7) NAM patients attested by the up-regulation of STAT6expression (11.5±5.1). In the same line 95.2% of NAM patients harbor complement membrane attack complex (C5b-9) deposits with 13.8±16.1% of muscle fibers decorated by C5b-9. Sarcolemmal C1q and IgG deposits are observed in all tested NAM patients (n=3).
Conclusion:
SRP+ and HMGCR+ NAM patients present mostly a NAM pattern with a randomly distributed necrosis (contrary to Jo-1+ patients) more pronounced in SRP+ patients. Nevertheless a subgroup of patients presents inflammatory infiltrates which could be involved partly in muscular necrosis. In addition the Th-2 immune response with signs of classical complement pathway activation suggests the pathogenic role of auto-antibodies.
Disclosure:
Y. Allenbach,
None;
A. Rigolet,
None;
B. Eymard,
None;
T. Stojkovic,
None;
A. Behin,
None;
P. Laforet,
None;
P. Hufnagl,
None;
N. Zerbe,
None;
T. Maisonobe,
None;
K. Mariampillai,
None;
S. Herson,
None;
O. Benveniste,
None;
W. Stenzel,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mechanisms-of-muscular-necrosis-in-auto-immune-myopathies-associated-with-anti-signal-recognition-particle-and-anti-3-hydroxy-3-methylglutaryl-coenzyme-a-reductase-antibodies-pathogenic-role-of-auto/