Background/Purpose: To investigate the expression of autophagy marker LC3, localization of macrophages and accumulation of misfolded proteins in myofibres of immune-mediated necrotizing myopathy (IMNM) muscle biopsies.

Methods: The analysis was made on muscle sections of 12 IMNM, 12 Dermatomyositis (DM), 5 Polymyositis (PM), 8 sporadic Inclusion Body Myositis (sIBM) patients and 6 healthy, age-matched controls immunolabelled with anti: -autophagy markers LC3b, -ubiquitin, – SQSTM1/p62, -TDP-43 (TAR DNA binding protein), -SMI31, -C5b-9, -CD68, -NCAM (neural cell adhesion molecule), -MHC I (major histocompatibility complex-I), -MHC II.

Results: In IMNM, inflammation was mild compared with DM, PM, sIBM; sporadic endomysial and/or perivascular inflammatory cells were CD68+ macrophages. The number of myofibres containing LC3b was statistically higher in IMNM and IBMs rather than in DM and PM.

In IMNM, LC3b was mainly located in regenerating myofibres, CD56 + and was associated with MHC-II⁺ vesicles. In sIBM, a high number of LC3b was found in vacuolated myofibers, whereas CD56+ myofibers appeared less pronounced.

SMI31 and p62 aggregates were significantly higher in sIBM rather than in the other IIMs, even if, also in IMNM they accumulated in non-necrotic myofibres, the latter colocalizing with LC3 as small puncta in IMNM myofibres and large vacuoles in sIBM myofibres. However, the highest number of ubiquitin⁺ myofibres was revealed in IMNM.

Conclusion: These findings suggest an involvement of cellular clearance systems in the pathophysiology of IMNM, like that of sIBM. LC3b⁺ puncta in regenerating myofibres can be considered a peculiar biomarker in IMNM. Further studies of larger patients cohorts are needed to better define IMNM.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autophagy-marker-lc3-accumulates-in-immune-mediated-necrotizing-myopathy-muscle-fibres/