S46 Abstracts / Neuromuscular Disorders 29 (2019) S37–S208 marked improvement only in patients with rapidly progressive dysphagia. This study identifies IBM and IMNM as the 2 most common causes of acquired myopathies with early or prominent dysphagia, accounting for approximately two-thirds of the patients in our cohort. Rapidly progressive course of dysphagia may predict immunotherapy responsiveness http://dx.doi.org/10.1016/j.nmd.2019.06.044 P.16 Cardiac and respiratory complications in necrotizing autoimmune myopathy J. Triplett , C. Kassardjian, T. Liewluck, A. Tahir, S. Kopecky, M. Milone Mayo clinic, Rochester, USA Necrotizing autoimmune myopathy (NAM) is an immune mediated myopathy (IMM) often associated with anti-3-hydroxy-3-methylglutaryl- coenzyme-A reductase antibodies (HMGCR-Ab) or signal recognition particle (SRP-Ab). Limited data exist regarding cardiac and respiratory dysfunction in NAM. We reviewed our neurology database (January 2004- October 2018) to characterize the cardiopulmonary features of NAM patients on the basis of antibody status and cardiac risk factors. We identified 109 NAM patients: 36 HMGCR-Ab (+), 18 SRP-Ab (+) and 58 antibody (-) [3 dual HMGCR-Ab and SRP-Ab (+).] Thirty-two patients had increased cardiac disease risk including coronary artery disease (n=10) and hypertension (n=28). Median age at diagnosis was 60 years (range 18- 86). Forty-three patients had dyspnea at presentation. ECG was abnormal in 55/86 patients (33/54 without cardiac risks), including prolonged QTc (n=31), conduction blocks (n=19), atrial or ventricular ectopics (n=10) and other nonspecific findings (n=21). Echocardiography was abnormal in 34/72 patients, including 19/45 without cardiac risks and 17/33 with dyspnea. Echocardiogram abnormalities included left ventricular diastolic dysfunction (LVDD) (n=31), systolic dysfunction (n=8) and pericardial effusion (n=2). An abnormal echocardiogram accompanied elevated troponins in 10/18 patients. LVDD improved in 4/11 patients following treatment. Among evaluated patients, pulmonary function tests were abnormal in 82% with all but one having changes suggestive of neuromuscular respiratory weakness; diffusing capacity of the lungs for carbon monoxide (DLCO) was reduced in 30%, and overnight oximetry revealed desaturations in 63%. Six patients had radiographic evidence of interstitial lung disease (ILD) [2 HMGCR-Ab (+) and 4 Ab (-)], accompanied by abnormal DLCO in the majority. This study revealed the majority of NAM patients exhibit cardiac and respiratory muscle dysfunction. Immunotherapy can improve echocardiographic abnormalities. ILD was a rare finding. Formal evaluation of cardiac and respiratory status should be included in the routine assessment of patients with NAM. http://dx.doi.org/10.1016/j.nmd.2019.06.045 P.17 Xenograft model of sporadic inclusion body myositis K. Britson 1 , K. Russell 2 , W. Tsao 1 , J. Montagne 1 , B. Larman 1 , K. Wagner 3 , L. Ostrow 1 , T. Lloyd 1 1 Johns Hopkins University, Baltimore, USA; 2 Thomas Jefferson University, Philadelphia, USA; 3 Kennedy Krieger Institute, Baltimore, USA Fundamental obstacles to the development of therapies for sporadic inclusion body myositis (IBM) include our limited understanding of disease pathogenesis as well as a lack of animal models. The primary invasion of myofibers by CD8+ T cells, an increased association of IBM with specific HLA haplotypes and other autoimmune diseases, and the presence of autoantibodies in many patients suggests that IBM is primarily an autoimmune disease. However, an association with aging, a lack of response to immunotherapy, and presence of ubiquitinated protein aggregates suggest the immune response may be secondary to myodegeneration. Here we describe a xenograft model of IBM we have developed to elucidate the pathogenesis of IBM and carry out pre-clinical therapeutic testing. In this model, human muscle biopsy specimens are transplanted into immunodeficient NOD-Rag1null-IL2rγ null mice. These transplanted myofibers die, but human muscle stem cells present in the xenograft subsequently expand and differentiate into new human myofibers which are spontaneously revascularized and innervated by the mouse host. Xenografts are collected at various post-operative timepoints and cryosectioned to carry out histochemical and immunohistochemical analysis. At 4 months, xenografts from non-myositis patients, myositis control patients, and IBM patients display successful regeneration. Regeneration appears less robust in IBM xenografts. This impairment is inversely correlated with the number of human CD3+ T cells in the xenograft and associated with sarcoplasmic MHC-I upregulation. Co-staining of CD8 and Ki-67 reveal that a majority of the CD8+ T cells within the IBM xenografts are proliferative at 4 months, and T cell receptor sequencing shows that T cells within the xenografts are oligoclonal. Preliminary experiments indicate that removal of these immune cells via low dose irradiation improves regeneration of IBM xenografts. In addition to these inflammatory features, at later timepoints, missplicing defects due to loss of nuclear TDP-43 can be detected, and IBM xenografts show rare fibers containing p62 positive aggregates. Thus, our xenograft model of IBM shows characteristic features of the human disease including protein aggregation and endomysial inflammation, and we are using this model for mechanistic studies and preclinical therapeutic testing in IBM. http://dx.doi.org/10.1016/j.nmd.2019.06.046 P.18 Comparing histological features and molecular gene expression in anti-Jo1-, anti-PL-7 and anti-PL-12 antibody-positive patients C. Preusse 1 , B. Paesler 1 , T. Ruck 2 , Y. Allenbach 3 , O. Benveniste 3 , N. Streichenberger 4 , S. Meuth 2 , W. Stenzel 1 1 Charité-Universitätsmedizin Berlin, Berlin, Germany; 2 University Hospital Münster, Münster, Germany; 3 Pitié-Salpêtrière Hospital, Paris, France; 4 Hospices Civils de Lyon, Lyon, France Some subgroups of idiopathic inflammatory myopathies are defined by myositis-specific autoantibodies, like the anti-synthetase syndrome (ASyS). These specific antibodies describe subsets of patients with distinct clinical phenotypes reflecting an underlying antigen-driven process, e.g. Jo-1 myositis is characterized by perifascicular necrosis, inflammation with MHC expression and unique myonuclear actin inclusions. The most frequently detected antibodies other than Jo1 are PL-7 and PL-12 also affecting a considerable proportion of patients. However, beyond some clinical descriptions there exist no in-depth characterization of PL-7/PL- 12 ASyS. Therefore, we focused on the detailed description of these subgroups, analyzing 40 patients using modern histopathology, qPCR, and electron microscopy to describe the disease more precisely. Besides clinical information, e.g. muscle affection, lung involvement, we quantified various morphological features like atrophy, necrosis, regeneration, MHC expression and cell infiltration. Of special interest are invading B and P cells, which we aim to characterize in combination with their attracting chemokines like CXCL13 or CXCR4. All three groups show similar histological features, but it became apparent that Jo1 + patients show a worse and more acute picture than PL-7/PL-12 + patients. In line with this results of the underlying immune response experiments with qPCR showed an upregulation of genes involved in a pro-inflammatory immune response in Jo1 (like strong upregulation of IFNG), whereas PL-7/PL-12 show a significantly increased expression of genes that are rather anti-inflammatory (e.g. upregulation of IL4R, TGFB). In conclusion, Jo1 + patients show different clinical features and appear more acute regarding the ongoing inflammation than PL-7/PL-12. Since the latter groups appeared very similar in terms of severity and accessory symptoms,