ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 282

From ‘immune Mediated Necrotizing Myopathy’ to ‘antibody-Mediated Necrotizing Myositis: Towards the Pathogenic Role of Anti-SRP and Anti-Hmgcr Antibodies’

Yves Allenbach1, Louiza Arouche-Delaperche2, Corinna Preusse3, Gillian Butler Browne2, Nicolas Champtiaux4, Kuberaka Mariampillai5, Aude Rigolet6, Peter Hufnagl7, Norman Zerbe8, Thierry Maisonobe9, Damien Amelin2, Sarah Leonard-louis10, Charles Duyckaerts11, Bruno Eymard12, Hans-Hilmar Goebel3, Laurent Drouot13, Olivier Boyer14, Olivier Benveniste2,5 and Werner Stenzel3, 1Pitié-Salpêtrière University Hospital, AP-HP, Department of Internal Medicine and Clinical Immunology, Paris, France, Paris, France, 2Sorbonne Universités UPMC Univ Paris 06, Myology research center, INSERM UMRS974, CNRS FRE3617, Pitié-Salpêtrière University Hospital, Paris, France, Paris, France, 3Charité - Universitätsmedizin, Department of Neuropathology, Berlin, Germany, Berlin, Germany, 4Department de Internal Medicine and Clinical Immunology, Hôpital Pitié-Salpêtrière, AP-PH, UPMC, Paris, France, 5Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Internal Medicine and Clinical Immunology, Hospital University Department: inflammation, immunopathology and biotherapy (DHU i2B), Paris, France, Paris, France, 6Internal Medicine, Pitié-Salpêtrière University Hospital, Paris, France, 7Pathology departmen, Charite Hospital, Berlin, Germany, 8Department of Pathology, Charite Hospital, Berlin, Germany, 9Pitié-Salpêtrière University Hospital, AP-HP, Department of Neuropathology, Paris, France, Paris, France, 10Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Neuropathology, Paris, France, Paris, France, 11Neuropathology, Pitie-Salpetriere Hospital, Paris, France, 12Department of Neurology, Hôpital Pitié-Salpêtrière, AP-PH, UPMC, Paris, France, 13Immunology, INSERM U905, University of Rouen, Rouen, France, 14Immunology, Inserm 905 & Institute for Biomedical Research, University of Rouen, Rouen, France

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , , ,

Session Information

Date: Sunday, November 13, 2016

Title: Muscle Biology, Myositis and Myopathies - Poster I: Basic/Translational

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.

Disclosure: Y. Allenbach, None; L. Arouche-Delaperche, None; C. Preusse, None; G. Butler Browne, None; N. Champtiaux, None; K. Mariampillai, None; A. Rigolet, None; P. Hufnagl, None; N. Zerbe, None; T. Maisonobe, None; D. Amelin, None; S. Leonard-louis, None; C. Duyckaerts, None; B. Eymard, None; H. H. Goebel, None; L. Drouot, None; O. Boyer, None; O. Benveniste, None; W. Stenzel, None.

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 .

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