staining of MHC-I, CD3 and CD20 molecules. According to the method of previous study on evaluating qMBS in juvenile dermatomyositis, the qMBS of adult IIM were evaluated in all patients at baseline (the time of muscle biopsy). Patients with a disease duration more than 6 months at baseline were assessed the Myositis Damage Index (MDI) according to IMACS outcome measures. All these patients were followed-up at least once then re-assessed MDI at last visit. The progression of MDI between baseline and last visit was used to represent the prognosis of IIM. Clinical data included myositis specific-autoantibodies (MSAs) status of all patients were collected.

**Results:** Patients with anti-TIF1-γ and anti-MDA5 antibodies had the highest and the lowest qMBS ($5 \pm 3.54$ vs $2 \pm 3.3$) at baseline within all patients. However there were no statistical significant difference among all MSAs subgroups. At baseline, 285 patients with disease duration more than 6 months were assessed MDI. There was positive correlation between qMBS and baseline MDI in anti-MDA5-positive subgroup ($r = 0.437, p = 0.042$) and negative correlation between qMBS and MDI in male patients ($r = -0.226, p = 0.039$). Of 105 patients with a minimum of 6 months of follow-up were re-assessed MDI at last visit. Mean follow-up for these patients was 19 months (range 25 - 75 months). In generalized linear model, patients with higher age of onset and longer duration of follow-up had increased risk of MDI progression ($B = 0.001$ and $0.002, p < 0.01$), respectively. Meanwhile, patients with anti-Mi-2 and anti-HMGCR-antibodies at diagnosis had decreased risk of MDI progression ($B = -0.037$ and $-0.063, p < 0.05$), respectively. However, for analysis of the correlation of qMBS and MDI outcome in combination with MSA subtype, we found that the higher qMBS at diagnosis in patients with anti-NXP2 and anti-MDA5 antibodies were associated with increased risk of MDI progression ($B = 0.022$ and $0.007, p < 0.05$), respectively.

**Conclusion:** The study suggested that evaluation of qMBS in combination with MSA subtype at diagnosis may be useful to predict the long-term outcome of adult IIM.

## P136

### Creatine Kinase in Systemic Sclerosis

Aurélien Chepy¹, Sandrine Morell-Dubois¹, Thomas Quémeneur², Eric Hachulla¹, Noémie Le Gouellec²

¹CHRU Lille Hopital Claude Huriez, Lille, France; ²Centre Hospitalier Valenciennes, Valenciennes, France

**Correspondence:** Aurélien Chepy

BMC Rheumatology 2019, **3**(Suppl 1):P136

**Context:** Elevated creatine kinase CK is frequent during systemic sclerosis (SSc) and associated with reduced survival.

**Objectives:** To describe the characteristics of patients with SSc and elevated CK, and identify the factors associated with the persistence of this elevation.

**Methods:** Forty-eight adult patients with SSc and high CK were identified among 541 SSc patients in Lille internal medicine department, tertiary center for autoimmune diseases. The diagnosis of SSc was based on ACR classification criteria. CK had to be measured at least twice and be at least once above the normal range (180 IU/L for women and 195 IU/L for men). Persistent elevation of CK was defined as at least 2 elevated CK measurements. Clinical, biological and imaging data were retrospectively collected.

**Results:** The sex ratio was 0.76 (21 men). Sixteen patients (33%) had diffuse cutaneous SSc (dcSSc), 31 (65%) had limited cutaneous disease (lcSSc) and one patient had a sine scleroderma type of SSc. Thirty-two patients (67%) had persistent elevation of CK. The following characteristics were associated with persistent elevated CK: a shorter delay between the onset of Raynaud phenomenon and the first rise of CK (7.5 ± 11.4 vs 14.9 ± 15.1 years, $p = 0.018$), an elevated CK-level at SSc diagnosis (71.9 % vs 25 %, $p = 0.005$), dcSSc (46.9 % vs 6.3%, $p = 0.008$), less frequent ACA (6 % vs 50 %, $p = 0.018$), the presence of muscle symptoms (56.3 % vs 6.3%, $p = 0.001$), a higher CK-level (786.2 ± 832 vs 223.5 ± 37.3 IU/L, $p < 0.001$) and a higher C-Reactive Protein (CRP) (15.8 ± 21.5 vs 3 ± 1.8 mg/L, $p = 0.007$). After a mean follow-up of 4.9 ± 3.6 years, myositis was suspected in 23 patients on the results of electroneuromyogram or muscle MRI. Muscle biopsy was performed in 16 patients in this group and found

myositis in 12 cases. Myositis was not diagnosed in any of the patients with transient elevation of CK.

**Conclusion:** In patients with SSc, the persistence of elevated CK was predictive of the occurrence of myositis. A diffuse cutaneous subtype of SSc, muscle symptoms, high level of CK at SSc diagnosis, CK-level over double normal values and CRP-level were predictive of a persistent elevation of CK in our cohort. Patients with these characteristics should be closely monitored for possible evolution toward myositis.

## P137

### PD-1 and PD-L1 inhibitors-associated myositis, Characteristic histopathological muscle pattern

Ana Matas¹, Albert Selva O'Callaghan², M. Noelia Antoniol¹, Sergio Prieto-González¹, Carlos Cabrera¹, Noemi Reguart¹, Gemma Vila Pijoan², Josep M. Grau¹, José C. Milisenda³

¹Hospital Clinic, Barcelona, Spain; ²Vall d'Hebron General Hospitalia, Barcelona, Spain; ³Hospital Clinic and IDIBAPS, Barcelona, Spain

**Correspondence:** Ana Matas; José C. Milisenda

BMC Rheumatology 2019, **3**(Suppl 1):P137

**Objectives:** Drug-induced myopathy is one of the most common causes of muscle disease. Recently, it has been described as an association between programmed death-1 (PD-1) inhibitors and immune-related adverse events affecting different organs including skeletal and cardiac muscle. Here, we describe the clinical and pathological findings of six unrelated patients with PD-1 and PD-L1 inhibitors-associated myopathy.

**Methods:** We did a retrospective study, analyzing our database from January 2017 to July 2018 where 317 muscle biopsies for diagnostic purposes were made. Two myology experts took care of the patients and, performed and analyzed muscle biopsies. Muscle biopsies were frozen in cooled isopentane, cryostat sectioned and stained and reacted routinely (minimum 16 staining's and reactions).

**Results:** We have identified 6 patients receiving anti-PD-1 or PD-L1 inhibitors suffering from either muscle weakness, asthenia, myasthenic syndrome-like, cardiac involvement, or other muscle related-symptoms. Muscle biopsy showed unequivocally showed an inflammatory myopathy in all of them. Furthermore, muscle biopsy showed in most of the cases a marked phenomenon of necrosis, and muscle regeneration with perivascular and endomial inflammatory infiltrates with a large component of macrophagic cells (figure 1). Also, a tendency to perifascicular atrophy was noted in some cases. The positivity of MHC class I antigens predominated in the perifascicular zones of the affected areas. MAC (C5b9) positivity was observed either in the sarcolemma or in the cytoplasm of some cells (Table 2). To note that serum muscle enzymes were elevated in only 3 patients (Table 1).

**Conclusion:** Although skeletal and cardiac muscle involvement as an adverse effect of anti-PD-1 inhibitors seems to the rare, it is important their early diagnosis in order to prevent a poor outcome. In addition, the pathological picture seems to be quite different from other inflammatory myopathies, with a prominent aggregate of histiocytes.

## P138

### Immune checkpoint inhibitor-associated myositis: a new and severe entity amongst immune inflammatory myopathies

Céline Anquetil, Joe-Elie Salem, Bénédicte Lebrun-Vignes, Douglas B. Johnson, Andrew L. Mammen, Werner Stenzel, Sarah Leonard-Louis, Olivier Benveniste, Javid J. Moslehi, Yves Allenbach

**Correspondence:** Céline Anquetil

BMC Rheumatology 2019, **3**(Suppl 1):P138

**Objectives:** Immune checkpoint inhibitors (ICI) therapy is an expanding field in cancer treatment. Immune-related adverse events (irAE) can potentially affect any organ system with a different tropism depending on the therapeutic targets (Programmed cell Death 1 (PD-1), PD-ligand 1 (PD-L1) or Cytotoxic T Lymphocyte-Associated Protein 4 (CTLA-4)). ICI-associated myositis was initially reported as a rare irAE
with an incidence of < 1% in the pivotal clinical trials. However, with the wide use of ICI, numerous patients harbored a new clinical and histological phenotype combining myositis, myasthenia gravis-like symptoms (especially oculomotor disorders and ptosis) and myocarditis. Importantly, ICI-associated myositis was a severe irAE with an overall mortality rate of 21.2%, increased to 51.7% in patients with concomitant myocarditis. We aimed to better characterize ICI-associated myositis patients and identify factors associated with poor outcome.

**Methods:** Data were collected from the VigiBase (http://www.vigiaccess.org/) and the World Health Organization database of individual safety case reports (Uppsala, Sweden) through November 2018. Cases were assessed using the High Level Term "Muscle infections and inflammations" of the Medical Dictionary for Regulatory Activities terms and at least one of seven ICIs.

**Results:** 277 myositis patients were identified in Vigibase with a dramatic increase in the reporting rate over the last years (before 2016, 0.5 case/month vs 11.7 cases/month in 2018). They received monotherapy in 83.4% of the cases, usually anti-PD1/ICl. We confirmed the specific phenotype previously described combining cardiotoxicity (20.9%, n= 58) including myocarditis (n=38) and myasthenia gravis-like symptoms (n=44). Other concurrent irAE were reported: hepatitis (n=20), colitis (n=8), nephritis (n=4), meningitis or encephalitis (n=4), thyroiditis (n=3), hypophysitis (n=3), and vitiligo (n=2). The overall mortality was 21% (n=54/257). In univariate analysis, the mortality rate was significantly higher in patients with concurrent cardiotoxicity (53.7% vs 12.3%, p< 0.0001) and in patients treated with combotherapy (anti-PD1 and anti-CTLA-4) compared to monotherapy (25.9% vs 19.6%, p=0.04). In multivariate analysis, cardiotoxicity and cancer progression were the two independent factors associated with fatal outcome (respectively, OR=9.7 p< 0.0001 and OR=15.2 p= 0.0002). The median time of myositis onset was 32 days [18.3-54.5] after the initial exposure to ICIs (data available in 88 patients). In the group of patients with fatal outcome, the median time of myositis onset was significantly shorter 18 days [14.5-23.5] vs 34 days [21-65] p=0.002.

**Conclusion:** Mortality in patients with ICI-associated myositis is related to cardiotoxicity and cancer progression. Moreover, severe form occurs early after the first infusion of ICI.

P139

**Mass cytometry reveals an impairment of B cell homeostasis in Anti-synthetase syndrome**

Gaelle Dzangué-Tchoupou¹, Yves Allenbach², Corinna Preusse³, Werner Stenzel³, Olivier Benveniste²

¹Center of research in Myology, Paris, France; ²Pitié-Salpêtrière University Hospital, Paris, France; ³Charité Universitätsmedizin Berlin, Berlin Germany

**Correspondence:** Gaelle Dzangué-Tchoupou

BMC Rheumatology 2019, **3**(Suppl 1):P139

**Background:** Myositis is a heterogeneous group of auto-immune disease involving several extra-muscular manifestations. Well-defined homogenous groups of myositis have been described e.g: inclusion body myositis (IBM), anti-3-hydroxy-3-methylglutaryl coA reductase (HMGR) myopathy, anti-signal recognition particle (SRP) myopathy and the anti-synthetase syndrome (ASyS). Patients with the ASyS present antibodies directed against amino-acyl-t-RNA synthetases, amongst which histidyl t-RNA synthetases (Jo1) antibodies are the most frequent. Recent data suggest the implication of B and NK cells in the physiopathology of ASyS anti-Jo1+ patients; nevertheless their role and activation states are poorly described. In addition, the implication of other cell types is poorly described.

**Objectives:** Our aim was to describe precisely and deeply the immune profile of the different cell subsets potentially involved in the physiopathology of anti-Jo1+ ASyS. This could allow a better comprehension of disease mechanisms and the identification of potential therapeutic targets.

**Methods:** We performed deep immune-profiling using 37 markers by mass cytometry on peripheral blood cells from 10 active untreated anti-Jo1 patients. Results were compared to those of 17 healthy

controls (HD) and a pool of 26 other active myositis control patients (IBM: n=10, anti-HMGR+ myopathy: n=9 and anti-SRP+ myopathy: n=7).

**Results:** We observed a decrease in the frequency of memory B cells in anti-Jo1 patients (mean±SEM: anti-Jo1 = 13±3%, HD = 37±4% and other myositis = 32±3), counterbalanced by an increase in the frequency of naïve B cells (mean±SEM: anti-Jo1 = 86±3%, HD = 61±4% and other myositis = 66±3). Interestingly, immunostainings of muscle biopsies from anti-Jo1 patients show perifascicular infiltrations of memory B cells, suggesting that they niche within the muscle. Activation markers such as CD95 and HLA-DR did not show any differences within B cells of Anti-Jo1+ ASyS patients in comparison to myositis controls. In line with the literature, we also observed an increase in the frequency of activated CD57+ CD56+ NK cells in anti-Jo1+ ASyS patients compared to control groups.

**Conclusion:** Here, we show an impairment of B cell homeostasis in anti-Jo1+ ASyS patients in comparison to other myositis patients and healthy subjects.

P140

**Anti-Jo1 positive myositis patients display a characteristic IgG Fc-glycan profile which is further enhanced in anti-Jo1 autoantibodies**

Catia Fernandes-Cerqueira, Nuria Renard, Antonella Notarnicola, Edvard Wigren, Susanne Gräslund, Roman Zubarev, Ingrid E. Lundberg, Susanna Lundström

Karolinska University Hospital, Stockholm, Sweden

**Correspondence:** Catia Fernandes-Cerqueira

BMC Rheumatology 2019, **3**(Suppl 1):P140

**Objectives:** IgG Fc-glycans affect IgG function and are altered in autoimmune diseases and autoantibodies. Anti-histidyl tRNA synthetase autoantibodies (anti-Jo1) are frequent in myositis associated with interstitial lung disease (ILD). We tested if total IgG Fc-glycans from Jo1+ versus Jo1- myositis patients and anti-Jo1-IgG showed characteristic differences, and if particular Fc-glycan features could be associated with specific clinical manifestations.

**Methods:** Total IgG was isolated by affinity purification from serum of 44 myositis patients (19 Jo1+ and 25 Jo1-) and 24 age/sex matched healthy controls (HC). Anti-Jo1-IgG was further purified from eleven patients using a recombinant Jo1-coupled affinity column. A shotgun proteomics approach was used to profile serum-derived IgG-Fc-glycans and IgG-chain distributions. Uni- and multivariate statistics were used to find characteristics and correlate data with clinical information.

**Results:** A high abundance of agalactosylated IgG1 Fc-glycans was observed in myositis patients compared to HC. Using intra-individual normalization of the main agalactosylated glycan (FA2) of IgG1 vs FA2-IgG2, myositis and HC were distinguished with an area under the curve (AUC) of 79±6%. For Jo1+ the AUCs went up to 88±6%. Bisected and afucosylated Fc-glycans were significantly lower in Jo1+ compared to Jo1- patients. Anti-Jo1 IgG enriched from eleven patients contained even lower abundance of bisected, afucosylated and galactosylated forms compared to matched total IgG. ASS and ILD diagnosis correlated with Jo1+ characteristic Fc-glycan features via multivariate analysis.

**Conclusion:** The anti-Jo1+ patient IgG Fc-glycan profile contains phenotype specific features which may underlie the pathogenic role of Jo1 autoantibodies.

P141

**Association of anti-Ro52 autoantibodies with interstitial lung disease and more severe disease manifestations in juvenile idiopathic inflammatory myopathies**

Sara Sabbagh¹, Iago Pinal-Fernandez¹, Takayuki Kishi¹, Ira Targoff², Frederick Miller¹, Andrew Mammen¹, Lisa Rider¹

¹National Institutes of Health, Bethesda, USA; ²Oklahoma Medical Research Foundation, Oklahoma City, USA

**Correspondence:** Sara Sabbagh

BMC Rheumatology 2019, **3**(Suppl 1):P141
**Objectives:** Myositis specific autoantibodies (MSA) and myositis associated autoantibodies (MAA) in adult and juvenile idiopathic inflammatory myopathies (JIM) confer specific phenotypes. In adults, anti-Ro52 autoantibodies (Abs) are associated with anti-synthetase (ARS) Abs and severe interstitial lung disease (ILD). There are few studies examining anti-Ro52 Abs in JIM. Our purpose was to define the prevalence and clinical features of anti-Ro52 Abs in a large cohort of JIM patients.

**Methods:** Sera from 307 patients with juvenile dermatomyositis (JDM), 26 patients with juvenile polymyositis (JPM), and 44 patients with juvenile connective tissue disease-myositis overlap (JCTM) were screened for anti-Ro52 Abs by ELISA. Clinical characteristics were compared between patients with and without anti-Ro52 Abs.

**Results:** Anti-Ro52 Abs were detected in 14% of JIM patients. Anti-Ro52 Abs were more common in patients with ARS Abs (64%, p < 0.001) and anti-MDA5 Abs (31%, p < 0.008). After controlling for the presence of MSAs, anti-Ro52 Abs were highly associated with ILD (36% vs 4%, p < 0.001), dyspnea on exertion (59% vs 25%, p < 0.001), and higher pulmonary scores at diagnosis (median 0.18 vs 0.08, p=0.004). Among anti-MDA5+ patients, Ro52 reactivity was associated with ILD: 70% (7/10) of anti-Ro52+ and 9% (2/22) of anti-Ro52- patients had ILD. Among ARS+ patients, 100% (9/9) of anti-Ro52+ and 40% (2/5) of anti-Ro52- patients had ILD (p=0.03). Patients with co-existing anti-p155/140 and anti-Ro52 Abs also had an increased frequency of ILD (15% vs 1%, p=0.03) and dyspnea on exertion (50% vs 16%, p=0.01) compared to anti-p155/140 positive patients who were anti-Ro52 negative. Anti-Ro52 Abs were also associated with more severe disease. Anti-Ro52+ patients more often had chronic continuous (78% vs 52%, p=0.05) and less often monocyclic disease course (3% vs 24%, p=0.02). Anti-Ro52+ patients were more often ACR functional class IV (11% vs 4%, p=0.008). Anti-Ro52 Abs were associated with an increased total number of medications received (mean 4.8 vs 3.8, p=0.04) and anti-Ro52+ patients more often received intravenous pulse steroids (79% vs 52%, p=0.03). Anti-Ro52+ patients less frequently had a remission (5% vs. 27%, p=0.05). Anti-Ro52 Abs had a weak association with HLA DRB1*1402 and DQA1*0503, which lost significance after adjustment for multiple comparisons.

**Conclusions:** Anti-Ro52 Abs are most prevalent in juvenile myositis patients with anti-MDA5 and ARS Abs. Even after adjusting for the presence of MSAs, anti-Ro52+ patients were more likely to have ILD and other pulmonary manifestations. Anti-Ro52+ patients have more severe disease with poorer outcomes.

P142

Anti-Jo-1 antibody-positive patients show different clinical symptoms, histological features and molecular gene expression compared to anti-PL-7 and anti-PL-12 antibody-positive patients

Barbara Paesler, Laure Gallay, Yves Allenbach, Olivier Benveniste, Nathalie Streichenberger, Werner Stenzel, Corinna Preuße
Charité Universitätsmedizin Berlin, Berlin, Germany

**Correspondence:** Barbara Paesler

BMC Rheumatology 2019, **3**(Suppl 1):P142

**Objective:** To compare skeletal muscle biopsies of patients with the three most common anti-synthetase syndrome-associated antibodies, using modern myopathologic methods in order to define common or divergent pathomechanisms.

**Methods:** Skeletal muscle biopsies from patients carrying one out of three anti-synthetase syndrome-associated antibodies Jo-1 (n=16), PL-7 (n=10) or PL-12 (n=13) were analyzed by histopathology, quantitative PCR, and electron microscopy.

**Results:** Evaluating the clinical history of 39 patients with anti-synthetase syndrome we discovered that anti-Jo-1 positive patients show eminently higher disease activity and more severe muscle symptoms than anti-PL-7 or anti-PL-12 positive patients. Thus, arthralgia and mechanic hands occurred more often, while anti-PL-7 or anti-PL-12 positive patients rather tended to show lung involvement and fever. All three groups showed similar histological features in typical topographic distribution, e.g. atrophic and necrotic myofibers

in the perifascicular region surrounded by infiltrating immune cells and prominently fragmented connective tissue. However, it became apparent that anti-Jo-1 positive patients showed a more severe and acute clinical picture than PL7/PL12+ patients. In keeping with this, qPCR analyses showed an up regulation of genes involved in a proinflammatory immune responses such as INFγ, TNFα, IL-6, IL-1β and STAT1 in muscle tissue derived from anti-Jo-1+ patients, whereas muscle from anti-PL-7+ and PL-12+ patients showed a significantly increased expression of cytokines providing rather profibrogenic and immune regulatory effects such as TGFβ and IL-4R. Of note, considerable amounts of plasma cells occurred in the skeletal muscle tissue of all three groups, accompanied by elevated levels of chemokines (CXCL12, CXCR4) and transcription factors (IL-6, APRIL, BAFF) that attract plasma cells and regulate their function. On the ultrastructural level, Jo1+ patients harbored intranuclear actin aggregates in about 75% whereas in PL7, and PL12+ patients they occurred more rarely. Conclusion: Anti-Jo-1 antibody-positive patients show distinct clinical features and their muscles appeared more severely affected as compared to muscle biopsies from anti-PL7 & -PL-12-positive patients. Conversely anti-PL-7 or anti-PL-12 positive patients appeared very similar in terms of milder skeletal muscle affection and non-muscular symptoms such as lung involvement. The striking occurrence of plasma cells in affected skeletal muscle tissue is overt in all three antibody groups and may therefore be considered as a characteristic and diagnostic feature of anti-synthetase syndrome-associated myositis. Based on their molecular profile we hypothesize that they may use the skeletal muscle as a survival niche.

P143

Hand Radiographic Lesions Are Frequent in Antisynthetase Syndrome Arthritis and Are Associated with a Longer Duration of the Disease

Cerise Guillochon-Petitcuenot¹, Gwenael Balazuc¹, Thibault Willaume¹, Guillaume Bierry¹, Francois Maurier², Naji Afif³, Laurent Messer⁴, Jacques-Eric Gottenberg¹, Jean Sibilia¹, Alain Meyer¹

¹Strasbourg University, Stasbourg, France; ²Hôpitaux Privés de Metz, Metz, France; ³Centre hospitalier de Mulhouse, Mulhouse, France;

⁴Hôpitaux civils de Colmar, Colmar, France

**Correspondence:** Alain Meyer

BMC Rheumatology 2019, **3**(Suppl 1):P143

**Objectives:** to report prevalence, characteristics and risk factors of radiographic abnormalities in antisynthetase syndrome (ASS) patients with joint involvement.

**Methods:** Mono-centric cohort of 101 patients with ASS was screened for hand X-ray availability. All the X-rays were read by two radiologists experienced in osteoarticular diseases. Patients with osteoarthritic lesions, chondrocalcinosis, gout or ACPA positive test were excluded from the analysis. ASS patients with hand radiographic lesions were compared to ASS patients with normal hand Xray.

**Results:** Twenty-four patients had at least one available hand X-ray, three were excluded because of osteoarthritic lesions or ACPA positivity. Thus, twenty-one were included followed during nineteen years (399 patient-years). Patients had history of arthralgia (n= 19), arthritis (n=15). Twelve patients (57.1%) had normal hand X-ray(s), while nine (42.9%) had radiographic lesions including: periarticular calcifications (77.8%), joint pinching (66.7%), subluxations (66.7%), erosions (22.2%) and demineralization (11.1%). Sex-ratio and age at diagnosis were not significantly different between the two groups. However, duration of ASS was much longer in the abnormal Xrays group (11 years IQR 5-18.5; vs 2 years IQR 0.5-6.5, p = 0.02), as was the duration of joint involvement (8 years IQR 2.3-15.5; vs 2 years IQR 0-5, p = 0.06). History of extra-articular involvements (fever, myositis, interstitial lung disease, Raynaud's phenomenon, sclerodactylia, mechanic's hands) did not differ between the two groups, except for calcinosis that tended to be more frequent in case of radiographic lesion (33.3 % vs 0%, p = 0.06). Distribution of anti-tRNA synthetase antibodies (anti-Jo1 n=15, anti-PL7 n=2, anti-PL12 n=1, anti-EJ n=3 and anti-OJ n=1) was similar in the two groups. Rheumatoid factor tended to be more frequently positive in case of radiological
abnormality (22.2 % vs 9.1 %, p = 0,57). Despite much higher disease duration, presence of persistent joint symptoms was similar in both groups (one third). However, patients with radiographic lesions did not receive significantly higher number of immunomodulatory drugs (1 IQR 0-2.8; vs 1 IQR 0-1.5, p = 0.48) and their dosage of corticosteroids at diagnosis of hand radiographic lesions tended to be higher than the patients without hand radiographic lesions at last X-ray (5 mg IQR 0-7.5; vs 1 mg IQR 0-6.5, p = 0.37). Handicap, evaluated by Health Assessment Questionnaire, tended to be higher in patients with radiographic lesions (0.85 IQR 0.3-1.2; vs 0.45 IQR 0.1-0.9, p= 0,49).

Conclusion: Hand radiographic lesions are frequent in ASS-arthritis and increase with duration of the disease.

P144

A rare case of anti-PL12 syndrome and Amyotrophic Lateral Sclerosis

Ejaz Shamim¹, Loraine Yarngo¹, Abigail Rapp², Christabel Chan², Melissa Sinkiewicz¹, Melvin Kong¹, Ivan Lim¹

¹Kaiser Permanente, Potomac, USA; ²The George Washington University, Washington, USA

Correspondence: Ejaz Shamim

BMC Rheumatology 2019, 3(Suppl 1):P144

Background: Idiopathic inflammatory myopathies (IIM) are a rare group of systemic muscle disorders. Amyotrophic Lateral Sclerosis (ALS) is the commonest of the motor neuron disorders. It is extremely rare that the two conditions occur together.

Objective: Here we describe a unique patient with IIM and ALS. Methods: in our neuromuscular multidisciplinary clinic in Kaiser Permanente MidAtlantic States, we follow patients with ALS and IIM from Washington, DC, Maryland and Virginia. This is a very rare case that has not been reported in the past.

Results: The patient is a left hand African American Male who initially presented to rheumatology department with joint swelling. His anti-CCP and anti-SSA were mildly elevated with elevation in the CK. Electromyographic (EMG) studies suggested chronic neurogenic changes in several cervical and lumbar nerve roots affecting distal and proximal muscles. Myopathic changes were also noted. MRI of the lumbar and cervical spine indicated degenerative joint disease. He started to develop mild proximal muscle weakness. He also started to have shortness of breath on mild exertion. Myositis specific antibody panel was sent as he also had mild proximal muscle weakness, revealing the presence of anti-PL 12 antibody. The result was confirmed. His pulmonary function tests were normal and continue to be normal. For the shortness of breath, no etiology was found. The patient had an EMG of the diaphragm which was suggestive of ALS. He had a muscle biopsy of the right thigh. It revealed chronic inflammation with scattered atrophic and necrotic muscle fibers. His muscle biopsy was sent for another opinion. In the meantime, he is being treated for ALS and for myositis. Compared to other ALS patients in our clinic, his progression is slower than expected.

Conclusion: Here we describe a rare instance of patient who has been diagnosed with ALS and meets Bohan Peter criteria for probably myositis with anti-PL 12 syndrome. He is being treated for both conditions. In a recent population-based study from Taiwan, 6 of more than 9,000 IIM patients with polymyositis had ALS. None were noted to have anti-synthetase syndrome.

P145

Diagnostic value of perifascicular HLA-DR expression in anti-synthetase syndrome associated myopathy

Jantima Tanboon, Michio Inoue, Ichizo Nishino
National Center of Neurology and Psychiatry, Tokyo, Japan

Correspondence: Jantima Tanboon

BMC Rheumatology 2019, 3(Suppl 1):P145

Objective: To assess diagnostic value of perifascicular (PF) HLA-DR expression for anti-synthetase syndrome associated myopathy (ASM)

Method: We retrospectively review 565 consecutive muscle biopsies with known associated myositis specific autoantibody (MSA) diagnosed as ASM (n=175), Dermatomyositis (DM, n=101) and immune mediated necrotizing myopathy (IMNM, n= 289) in National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan. Immunohistochemical study including HLA-ABC, HLA-DR, C5b-9, and MxA are available in all cases. ASM and IMNM include in study cohort are negative for MxA. Inclusion body myositis (IBM) is not included in this study. We evaluate HLA-DR expression pattern by classifying it into 5 categories: 0 = negative staining, 1 = scattered or patchy HLA-DR staining muscle fibers without definite PF localization, 2 = a few to several discontinuous HLA-DR positive fibers with PF localization, 3 = small number of (2-5) continuous HLA-DR positive fibers with PF localization, 4 = large number of continuous HLA-DR positive fibers with PF localization involving at least one side of a fascicle, 5 = large continuous HLA-DR positive fibers with PF localization plus > 10 positive fibers scattered in fascicles. We postulate significant PF expression for category 4 and 5.

Result: HLA expression is most commonly present in ASM (54.3%, 95/175) follow by DM (27.9%, 28/101) and IMNM (4.8%, 14/289: anti-SRP IMNM 5/170 and anti-HMGCR IMNM 9/119), respectively. Category 4 and 5 expressions are most commonly present in ASM (38.3%, 67/175) and occasionally and rarely present in DM (7.9%, 8/101) and IMNM (0.3%, 1/289), respectively. Anti-Jo1 associated myopathy is the most common ASM subtype associated with HLA-DR expression (60.7%, 34/56).

Conclusion: Perifascicular HLA-DR expression may help narrow scope of muscle pathology differential diagnosis to ASM especially anti-Jo-1 associate myopathy in MxA negative case.

P146

Interstitial lung disease in Idiopathic Inflammatory Myopathies: ultrasound assessment of pleural irregularities and comparison with clinical, serological and functional aspects

Elisa Cioffi, Simone Barsotti, Chiara Romei, Alessandra Tripoli, Claudia Roncella, Chiara Cardelli, Marts Mosca, Fabio Falaschi, Rossella Neri University of Pisa, Pisa, Italy

Correspondence: Elisa Cioffi

BMC Rheumatology 2019, 3(Suppl 1):P146

Background: Interstitial Lung Disease(ILD) is one of the most frequent and significant extra-muscular manifestations in Idiopathic Inflammatory Myopathies(IIM). Recently, several authors proposed ultrasound-US quantification of pleural irregularities(PIs) as a possible method to detect ILD in IIM patients. The objective of our study was to evaluate the prevalence of PIs and to compare the results obtained to clinical symptoms/signs, autoantibodies, high resolution chest TC(HRCT) and Pulmonary Function Test(PFT).

Methods: 45 patients(30 females, 15 males, mean duration disease 54.4 ±86.1 months, median age 63.6±11.9 years) with a diagnosis of IIM according to Bohan and Peter criteria (19PM, 20DM, 1MCI, 3ovер-lap and 1paraneoplastic form) who required HRCT evaluation were enrolled. Data collected included presence of anti-synthetase autoantibodies(ASS), dyspnoea assessment by means MRC scale, PFT parameters, questionnaires as Leicester Cough Questionnaire(LCQ) and Saint George Respiratory Questionnaire(SGRQ). Thoracic US evaluation in 53 anterior and posterior thoracic areas was performed using a high frequency 8-18MHz linear probe. We evaluated the pleural profile aspect assigning each space a score (regular=0, mild irregular=1, irregular=2), the sum of the scores at anterior, posterosuperior, posteroinferior and the total PIs score were calculated. HRCTs were assessed by an expert radiologist for the presence of signs of ILD.

Results: The mean PIs total score obtained with lung US was 26.6±13.9(anterior 10±6.5, posterosuperior 4.8±4.4 and posteroinferior 11.7±6). Patients with ILD at HRCT had a PIs total score significantly higher than patients without ILD (p= 0.003) and it was true also for the singular lung sites, especially for the posteroinferior (p= 0.001) and posterosuperior (p= 0.032) areas. Dyspnoea more than2 MRC scale was related with a different mean PIs total score compared to dyspnoea less-equal 2MRC scale (p=0.01). The presence of oough
and fine crackles at the thoracic auscultation were associated to higher PIs score (respectively p= 0.049 and p=0.001), particularly in posterosuperior areas. Also, the LCQ significantly correlated with the PIs total score (p=0.02, r=-0.448), particularly in the posterosuperior areas(p=0.02,r=-0.446). Patients with ASS (p= 0.002) and particularly anti-Jo1 (p= 0.001), showed a PIs total score significantly higher than patients without ASS. FEV1(p=0.001, r=-0.591), TLC(p=0.001,r=-0.695) and LCO(p=0.004,r=-0.532) significantly correlated to the US PIs score.

**Conclusions:** The US PIs score is correlated to presence of ILD, clinical, serological and functional parameters in patients with IIM-related ILD and may improve the bedside evaluation of the patient in the routine clinical practice. Further studies are needed in particular to assess the prognostic value of lung ultrasound in IIM

## P147

### A case of myositis with positive anti-PM/Scl antibody

Suur Bilciler, Ali Reza Shoraka
UTHealth Science Center, Housten, USA

**Correspondence:** Suur Bilciler
BMC Rheumatology 2019, **3**(Suppl 1):P147

**Introduction:** Even though Anti-PM/Scl is a common marker of either systemic sclerosis or its overlap syndromes pathological findings in muscle and clinical presentation of patients harboring this antibody is very variable.

**Case Presentation:** We present a case of 71 year-old female with sub-acute progressive weakness which started in legs then progressed to arms and face over three months. She developed head drop within six months of presentation. Patient was found to have telangiectasias, weakness upper more than lower extremities, proximal more than distal, head drop and bilateral scapular winging, scaly finger tips with no ulcers or necrosis. On further workup, she showed myopathic changes in EMG and muscle biopsy showed dense collections of inflammatory cells in a nodular fashion. Laboratory work up showed elevated CK, ESR, high titer ANA and positive double-stranded ANA, rheumatoid factor and anti-PM/Scl antibody. Genetic testing was negative for known muscular dystrophies including fascioscapulohumeral dystrophy. Although voltage gated potassium channels complex antibody was found in serum, malignancy workup was negative. She was started on steroid treatment followed by addition of steroid sparing agents. Her lower extremity weakness improved significantly in lower extremities with some improvement in arm and neck muscles. Our case did not meet criteria for systemic sclerosis.

**Conclusions:** The fact that our patient has prominent cervico-brachial weakness is compatible with previous cases. There are few studies that show anti-PM/Scl antibody prevalence in patients with no definite systemic sclerosis upon presentation. Such cases are important to determine and diagnose to improve our knowledge about disorders related of positive anti-PM/Scl antibody.

## P148

### Anti-tRNA Synthetase and PmScl antibody status is associated with distinct immunophenotypes irrespective of clinical classification

Erin Wilfong, Katherine Vowell, Leslie Crofford, Peggy Kendall
Vanderbilt University, Nashville, USA

**Correspondence:** Erin Wilfong
BMC Rheumatology 2019, **3**(Suppl 1):P148

**Introduction:** In 2015, the ATS/ERS published preliminary classification criteria for interstitial pneumonia with autoimmune features (IPAF) with a goal of identifying patients with interstitial lung disease who might benefit from immunosuppression. The inclusion of the myositis associated antibodies – particularly the anti-tRNA synthetase (ARS) and anti-Pm/Scl antibodies – has been debated as clear systemic syndromes have been described for these antibodies. Here, we aimed to investigate the immunophenotypes of patients with both ARS and anti-Pm/Scl antibodies and ascertain if immunophenotypes correlated with clinical classification criteria or serologic status.

**Method:** Peripheral blood mononuclear cells (PBMCs) were collected from 12 patients with idiopathic inflammatory myopathy (IIM) or IPAF; patients were phenotyped by chart abstraction. Clinical classification was performed using the 2015 IPAF and 2017 ACR/EULAR IIM criteria. 18 healthy controls were used for comparison. Cryopreserved PBMCs were subjected to cytometry by time of flight (CyTOF) to investigate B, T, and innate cell subsets. Analysis was performed in Cytobank using unsupervised multiparameter methods as well as traditional biaxial gating. Statistical significance was determined with Mann-Whitney tests.

**Result:** 6/12 patients met classification criteria for IIM; the remainder met criteria for IPAF. Serologically, 5 patients were anti-PmScl positive, 2 were anti-Jo1 positive, 2 were anti-PL7 positive, 2 were anti-PL12 positive, and 1 was anti-EJ positive. All patients required escalation of immunosuppression at enrollment due to active disease. Compared to healthy controls, several B- and T-cell populations were decreased for all clinical and serologic statuses, including class-switch and unclass-switched memory B-cells, T follicular helper cells, and CXCR5+PD1- central memory CD4+ T-cells. Patients with anti-Jo1 or anti-PmScl antibodies had increased frequency of classical monocytes compared to non-Jo1 ARS patients or healthy controls (27.5% vs. 12.61% and 7.73%, p=0.03 and p=0.002). Compared to other positive serology and healthy controls, patients with anti-Jo1 antibodies had increased frequency of CXCR4+CD21lo B-cells (53% v. 1.6% and 0.79%, p=0.03 and p=0.02), CD8+CD11c+CD38- T cells (12.84% vs. 0.2% and 0.2%, p=0.03 and p=0.01), and CD4+CXCR4hi naïve T cells (21.7% vs. 0.29% and 0.01%, p=0.03 and p=0.01).

**Conclusion:** Various anti-tRNA synthetase and anti-PmScl antibodies are associated with distinct immunophenotypes. These immunophenotypes may serve as biomarkers if verified in larger cohorts and may also inform treatment strategies in patients who have similar clinical phenotypes but divergent underlying immunologic pathophysiology.

## P149

### Autoantigen Histidyl-tRNA Synthetase (HisRS) is secreted into circulation and inversely correlates with anti-HisRS autoantibody levels

Catia Fernandes-Cerqueira¹, Ryan Adams², Antonella Notarnicola¹, Andrea Cubitt², David J. King², Ingrid E. Lundberg¹, Per-Johan Jakobsson¹, Leslie A. Nangle²

¹Karolinska University Hospital, Stockholm, Sweden; ²aTyr Pharma, San Diego, USA

**Correspondence:** Catia Fernandes-Cerqueira
BMC Rheumatology 2019, **3**(Suppl 1):P149

**Objectives:** Histidyl-transfer RNA synthetase (HisRS) is a cytoplasmic enzyme and a major autoantigen in idiopathic inflammatory myopathy (IIM) and anti-synthetase syndrome (ASS). We investigated if HisRS is detectable in circulation and whether the free extracellular HisRS levels correlate with anti-HisRS autoantibodies.

**Methods:** HisRS and anti-HisRS autoantibodies were quantified in sera from 357 IIM/ASS patients (61 anti-HisRS+ and 286 anti-HisRS-) and 115 age/gender matched healthy controls (HC). Levels of HisRS antigen were measured by an immunoassay employing two non-competing monoclonal antibodies targeting the N-terminal (WHEP) domain of HisRS. Anti-HisRS autoantibodies were accessed by an immunoassay which used a commercial N-terminal HARS monoclonal antibody. Interstitial lung disease (ILD) status was present in 51 of 70 anti-HisRS+ IIM/ASS patients.

**Results:** HisRS was detectable in circulation with higher levels in patients with IIM/ASS compared to HC. When subgrouping patients into autoantibody status (Jo1+ vs Jo1-) significantly lower levels of serum HisRS (3 pM) were detected in anti-HisRS+ IIM/ASS patients, compared to anti-HisRS- IIM/ASS and matched HC and (13 pM and 8 pM, respectively p < 0.001). Levels of free HisRS in HC were also significantly lower in comparison to the anti-HisRS- IIM/ASS group (p < 0.001). IIM/ASS diagnosed with ILD had significantly lower serum HisRS levels (6 pM) compared to IIM/ASS patients without ILD (11 pM, n=209). This observation may reflect the fact that a large
majority of anti-HisRS+ IIM/ASS were diagnosed with ILD (86%). Al-
though the low number of anti-HisRS+ IIM/ASS patients without ILD
in our cohort (n=7), we nonetheless observed slightly elevated serum
HisRS levels in this group (5 pM), compared to 3 pM in anti-HisRS+
IIM/ASS diagnosed ILD (n=44). Presence of anti-HisRS autoantibodies
in serum of anti-HisRS+ IIM/ASS individuals correlated negatively with
levels of free HisRS (Spearman correlation r=-0.57; p < 0.0001).

Conclusion: The identification of HisRS autoantigen in serum, and the inverse correlation between levels of HisRS and cognate anti-HisRS antibodies in circulation may explain the access autoantibodies have to intracellular targets. Free extracellular HisRS may exert unknown non-canonical functions which may be impaired in Jo1+ IIM/ASS due to neutralization by the anti-HisRS autoantibodies, and consequently contributing to IIM/ASS pathogenesis.

P150

Course of interstitial lung disease in antisynthetase syndrome with
immunosuppressive therapy

Linn Riedel, Jens Schmidt, Jan-Gerd Rademacher, Radovan Vasko, Peter
Korsten

Universitätsmedizin Göttingen, Göttingen, Germany

Correspondence: Peter Korsten

BMC Rheumatology 2019, 3(Suppl 1):P150

Objectives: The antisynthetase syndrome (ASS) is characterized by the presence of myositis, fever, arthritis, raynaud's phenomenon, mechanic's hands and interstitial lung disease (ILD). While not present in all patients, ILD represents a major organ complication, potentially leading to pulmonary fibrosis and increased mortality. While various treatment regimens have been used, there are no consensus guidelines on how to optimally treat patients with ASS-ILD. Therefore, we aimed to analyze the disease course of patients at our center.

Methods: This is a single-center retrospective observational trial of prospectively collected routine medical data. Patients were identified by the presence of anti-tRNA-synthetase-antibodies (ARS) through our laboratory's database. Patients were included if ILD was present and if sufficient data were available for further analysis. Immunosuppressive treatment regimens were recorded. As outcome measures, we analyzed creatinine kinase levels and pulmonary function tests (PFT, forced vital capacity, FVC, and diffusion capacity of carbon monoxide, DLCO) at various time points (0-6, 7-12, and >12 months after first diagnosis). Also, we quantitatively assessed pulmonary fibrosis/infiltrates with Pixmeo OsiriX Lite software on computed chest tomography (CT) scans before and during treatment.

Results: 27 patients with ASS were identified. Of these, 13 were ex-
cluded because they did not have ILD. Of the remaining 14 patients
(51,8%) 10 were female (71,42%), and 4 were male (28,57%). Median
disease duration was 51 months, follow-up was 21 months. Of these,
12 (85,71%) received treatment with glucocorticosteroids, 7 (50%)
azathioprine, 6 (42,9%) methotrexate, 1 (7,1%) mycophenolate, 2
(14,3%) leflunomide, 6 (42,9%) rituximab, 3 (21,4%) cyclophosphamid,
1 (7,1%) cyclosporine, and 1 (7,1%) tocilizumab. Median CK level at
diagnosis was 673,5 U/L, which decreased to 78,5 U/L, 78 U/L, and 83
U/L after 6, 12 and >12 months, respectively. Pulmonary function
testing was only inconsistently assessed. Quantitative fibrosis score
analysis on CT scans showed a marked decrease during treatment.

Conclusions: Our data suggest that immunosuppressive treatments are effective in reducing CK levels. ILD improved or stabilized in all but one patient. CT scans showed a reduction of areas with ILD in the majority of patients undergoing immunosuppressive therapies. Our data suggest that a standardized fashion of ILD assessment in myositis patients is warranted. Glucocorticoid treatment is effective in improving CK levels and ILD findings. However, all patients required additional immunosuppression, mostly with azathioprine or rituximab, to achieve an improvement of ILD on chest imaging.

P151

Association between pathological features of skeletal muscle and
clinical phenotypes in anti-synthetase syndrome

Xiaolan Tian, Lining Zhang, Hhongxia Yang, Yamei Zhang, Wenli Li,
Qingyan Liu, Qinglin Peng, Xin Lu

China-Japan Friendship Hospital, Beijing, China

Correspondence: Xiaolan Tian

BMC Rheumatology 2019, 3(Suppl 1):P151

Objective: To analyze the characteristics of skeletal muscle involve-
ment and muscle pathology in patients with anti-synthetase syn-
drome (ASS).

Methods: 486 patients with idiopathic inflammatory myopathy (IIM) diagnosed in China-Japan Hospital from May 2008 to March 2018 were retrospectively analyzed. All patients underwent muscle biopsy. According to the pathological characteristics of muscle biopsy, they were divided into six pathological types: pathologic DM (pDM), pathologic PM (pPM), unspecified myositis(USM), necrotizing myositis (NAM), and MHC-I group and the normal pathological group. Immunoblotting was used to detect myositis specific antibody (MSA). The relationships between the clinical features of different anti-synthetase antibodies and the pathological features of muscle biopsy were analyzed.

Results: Among 486 IIM patients, 77 (15.8%) were positive for anti-ARS antibody, 55 (70.5%) were female, the onset age was 50.1±11.6 years, and the disease course was 21.8 ±42.7 months. The most commonly seen subgroup was the Anti-Jo-1 antibody positive patients (36 cases, 7.4%), while the anti-PL-7 positive patients with 22 cases (4.5%), anti-PL-12 positive patients with 9 cases (1.9%), anti-EJ positive patients with 10 cases (2.1%) and no anti-OJ antibody positive patients. There was no significant difference in the characteristics of muscular and extramuscular involvement between the groups. The most commonly seen pathological type of muscles was USM (37 cases, 48.1%), followed by pDM (14 cases, 18.2%), the normal pathological group (13 cases, 16.9%), NAM group (10 cases, 13.0%) and MHC-I group (3.9%), and no patients of pPM. There was no statistical difference in the pathological characteristics of muscle among the antibody subgroups. There were 16 CADM patients and 61 non-CADM patients. The proportion of patients with normal muscle pathology in the former group was higher than that in the latter group. Perifascicular lesions including perifascicular atrophy and perifascicular necrosis were rare in patients with ASS.

Conclusion: ASS is a subtype of IIM with relatively high homogeneity.
Muscle involvement is common and the pathological characteristics
of muscle are not specific.

P152

The experience of Juvenile Dermatomyositis described through
poetry

Polly Livermore, Lucy R. Wedderburn, Faith Gibson
Great Ormond Street Institute of Child Health, London, UK

Correspondence: Polly Livermore

BMC Rheumatology 2019, 3(Suppl 1):P152

Objectives: Juvenile Dermatomyositis (JDM) is a rare, potentially life-threatening condition with no known cure. There is no research to date that documents how children and young people feel about their condition, from their perspective. This study asked children and young people what it is like to have JDM. Presented here are their experiences told through the medium of poetry.

Methods: Interpretive Phenomenology interviews aided by creative methods, were used to capture the lived experience. Data were obtained from 15 young people with JDM, between 8 and 19 years of age from one tertiary institution's Paediatric Rheumatol-
ogy department in the UK using audio-taped interviews. Data were analysed phenomenologically, using a process that derives narratives from transcripts resulting in a phenomenon which is evident in the experiences shared. The data were crafted into stories. During this process, the words of the young people were shaped into ‘research poems’ which illustrate the real emotions and experience of children and young people living with JDM.

Results: Fifteen stories were crafted, with one phenomenon and five shared narratives for each of the five themes identified. Eleven individual poems have been constructed. Titles of which reflect these experiences, such as ‘Tomato face’ and ‘The day my JDM came to town’. An example of a poem follows: Worry “You give me a name that I can’t say, But I have to explain what it is every day, I’m 10 now, but I worry about what my JDM is doing to me, It’s not easy to see, But I know it’s there, Inside me”.

**Conclusion:** This study is the first of its kind to ask young people to talk about what it is like to have Juvenile Dermatomyositis. This process of reducing the transcripts into poetry will be discussed and all the poems will be presented for the first time as a powerful method of sharing real life voices from young people themselves. The results will aid clinicians to gain a deeper understanding of what daily life is like for these young people, and provide ideas on how to enhance psychosocial functioning. Through sharing these poems it will encourage health professionals to consider the impact JDM has, not only on the physical health, but more importantly, the impact on a young person's psychological well-being.

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