Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Immune mediated necrotizing myopathy (IMNM) has been recently added as a new entity among dermatomyositis, polymyositis and sporadic inclusion body myositis. IMNM is defined by predominant muscle fiber necrosis and no or few inflammatory infiltrates. Two auto-antibodies are held to be specifically associated with IMNM: the anti-signal recognition particle antibody (SRP) and anti-3-Hydroxy-3-Methylglutaryl-CoA Reductase antibody (HMGCR). Those antibodies target ubiquitous cytoplasmic proteins. The clinical phenotype of SRP and HMGCR patients is characterized by severe proximal weakness of skeletal muscles, whereas extra-muscular manifestations are mild or absent. However, it is unknown to which extent pathological features are similar and muscular immune mechanisms especially those involved in the necrosis are largely unknown. It is crucial to gain insight in pathophysiology of the disease regarding its severity and refractory course.
Methods: Thus, we aim to precisely describe the morphology of skeletal muscle alterations of both conditions in a series of SRP and HMGCR patients, and analyze molecular immune mechanisms at the muscular level. Muscle biopsies from SRP (n=25) and HMGCR (n=19) patients were analyzed and compared to myositis patients (Jo-1, n=21 and dermatomyositis, n=7).
Results: SRP patients have the most important muscle deficit compare to HMGCR, Jo1 and dermatomyositis patients. Along that line, CK levels in SRP patients were the highest whereas the DM group had the lowest values. SRP patients showed the highest proportion of necrotic fibers and strikingly this proportion was similar in HMGCR and Jo1 patients. However, necrosis occurred in perifascicular regions only in Jo-1 patients, whereas it was randomly distributed in SRP and HMGCR patients. Creatine kinase levels correlated with proportion of necrotic fibers. Regeneration of fibers also correlated with necrosis and occurred much more frequently. Inflammation was regularly observed. Macrophages were the most abundant but T cells densities were in a quarter of cases in the same range as myositis controls. In addition, presence of T cells densities in SRP and HMGCR patients correlated with the proportion of necrotic fibers. qPCR and immunohistochemistry analysis showed the presence of classically activated macrophages in a Th-1 immune environment. These M1 macrophages were involved in myophagocytosis. In addition, humoral immunity with activation of the classical pathway of the complement cascade was observed. This was accompanied by a sarcolemmal immunoglobulins depositions and alternatively activated macrophages. Finally, positive membrane staining for SRP and HMGCR proteins were detected both in vitro (primary muscle cells culture) and in vivo(muscle biopsies for IMNM patients) on some muscle fibers.
Conclusion: SRP and HMGCR myopathies can no longer be considered as non-inflammatory myopathies since the inflammation is correlated with muscle necrosis, which involves humoral immunity including myositis-specific autoantibodies.
To cite this abstract in AMA style:Allenbach Y, Arouche-Delaperche L, Preusse C, Butler Browne G, Champtiaux N, Mariampillai K, Rigolet A, Hufnagl P, Zerbe N, Maisonobe T, Amelin D, Leonard-louis S, Duyckaerts C, Eymard B, Goebel HH, Drouot L, Boyer O, Benveniste O, Stenzel W. From ‘immune Mediated Necrotizing Myopathy’ to ‘antibody-Mediated Necrotizing Myositis: Towards the Pathogenic Role of Anti-SRP and Anti-Hmgcr Antibodies’ [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/from-immune-mediated-necrotizing-myopathy-to-antibody-mediated-necrotizing-myositis-towards-the-pathogenic-role-of-anti-srp-and-anti-hmgcr-antibodies/. Accessed November 29, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/from-immune-mediated-necrotizing-myopathy-to-antibody-mediated-necrotizing-myositis-towards-the-pathogenic-role-of-anti-srp-and-anti-hmgcr-antibodies/