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Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of new-onset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARS-COV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link. Disclosure A. Storrie: None. R.M. Hum: None. J. Lilleker: None. P. Ho: None.

Background/Aims An area of key unmet need in psoriatic arthritis (PsA) is the identification of biomarker(s) which predict those likely to respond to a specific therapy; in order to achieve that, an objective measure of disease activity would be ideal. Ultrasound power Doppler (PD) is a semi-quantitative measure of inflammation. However, ultrasound is time-consuming and requires specific expertise, whereas a blood-based surrogate biomarker of PD would be easier to apply clinically, and could serve as an objective outcome measure of response. Our aim is to identify proteomic biomarkers associated with PD in PsA patients. Methods Twenty-six patients with PsA (fulfilling CASPAR criteria) were recruited prospectively. All underwent 66-joint ultrasound examination and presence of PD was recorded. There were 7 patients without PD(-) and 19 with PD(+) detectable in at least 1 joint. Proteomics data for 1,073 proteins were generated using sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH MS). Proteins with high levels of missing data were filtered (>30%) followed by random forest analysis. Differentially expressed proteins (DEPs) based on PD status were identified. Protein-protein interaction network analysis was performed using the search tool for retrieval of interacting genes (STRING), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). Results Following pre-processing, 553 proteins were available for analysis. Seventeen DEPs were identified (p-values Conclusion We identified several potential serum proteomic biomarkers correlated with disease activity, as assessed by the presence of PD, in PsA; these provide insights into the biological mechanisms underlying synovitis in PsA. Validation in a larger cohort and functional studies are required to determine the role of these proteins in mediating inflammation in PsA. Disclosure R.M. Hum: None. N. Nair: None. S.F. Ling: None. A. Barton: None. P. Ho: None. D. Plant: None.

We present a case of certolizumab-associated renal sarcoidosis, the first reported case in a patient with psoriatic arthritis (PsA) that was effectively treated with corticosteroids. A 55-year-old Caucasian man with PsA diagnosed at age 47 and plaque psoriasis since his early twenties was on certolizumab pegol (CZP) for 7 months before presenting to the emergency department with seizures and renal failure. A renal biopsy confirmed renal sarcoidosis. His CZP therapy was stopped, and after several months taking prednisolone at a reducing regime, his renal function improved, and his PsA remained under control. When considering further treatment options for his PsA keeping in mind that other drugs, especially tumour necrosis factor-alpha inhibitors, have been reported to be associated with sarcoidosis, tofacitinib was considered to be a future treatment option acceptable to the patient, given current National Institute for Health and Care Excellence guidelines approving its use in PsA and the lack of reports of tofacitinib-associated sarcoidosis in the literature.

Objectives Interventions aimed at increasing TNF-α inhibitor serum drug levels (SDLs) may improve treatment response; however, previous studies suggesting SDL cut-offs have not accounted for treatment adherence. The aim of this study was to establish the relationship between adalimumab/certolizumab SDLs and EULAR good vs non-/moderate response and to define SDL cut-offs associated with good response in fully adherent patients. Methods In a prospective observational study, 475 patients with RA were treated with certolizumab (n = 192) or adalimumab (n = 283). At baseline and 3, 6 and 12 months, patients had 28-joint DAS, self-reported treatment adherence and SDLs measured. Fully adherent patients were analysed as a subgroup. Follow-up data at 3, 6 and 12 months were analysed separately. Median SDLs were compared in good vs non-/moderate response patients and receiver operating characteristics (ROC) curves were used to establish cut-off SDLs. Results Fully adherent good responders had significantly higher median adalimumab/certolizumab SDLs compared with non-/moderate responders (P = 0.04 and P = 0.0005, respectively). ROC analysis reported 3 month non-trough adalimumab SDLs discriminated good vs non-/moderate response with an area under the curve (AUC) of 0.63 (95% CI 0.52, 0.75), with a cut-off of 7.5 mg/l being 39.1% specific and 80.9% sensitive. Similarly, 3 month non-trough certolizumab SDLs discriminated good vs non-/moderate response with an AUC of 0.65 (95% CI 0.51, 0.78), with a cut-off of 26.0 mg/l being 43.9% specific and 77.8% sensitive. Conclusion In fully adherent patients, higher SDLs are detected in good responders, suggesting that interventions to improve SDLs, such as encouraging adherence, could improve treatment response. The 3 month non-trough SDL cut-offs of 7.5 mg/l for adalimumab and 26.0 mg/l for certolizumab may be useful in clinical practice.

Background/Aims Mycoplasma hominis is a commensal bacterium of the genitourinary tract which can be associated with infection in immunocompromised patients. Colonisation with M. hominis has been associated with reactive arthritis and septic arthritis. We describe a case of M. Hominis septic arthritis in a patient with SLE on maintenance immunosuppression. Methods A 27-year-old woman presented with a 2-week history of a swollen left elbow and fatigue which affected her ability to work. Otherwise, she was systemically well and afebrile. She had an established diagnosis of SLE since she was aged 8 years, and her SLE had included mucocutaneous, central nervous system, renal involvement, and haemolytic anaemia. Her SLE was controlled on azathioprine, hydroxychloroquine, and prednisolone 5mg daily. Clinical examination revealed a mildly warm, non-erythematous, tender and swollen left elbow with a 40° flexion deformity. Initial investigations showed raised CRP 41mg/L and ESR 32mm/hr. White blood cell and platelet count were normal. Procalcitonin was insignificant at < 0.1ng/mL. Complements and urine analysis were normal, and dsDNA was negative. X-ray of the left elbow showed joint effusion. Ultrasound revealed active synovitis, subcutaneous oedema and purulent material in the joint. The fluid aspirate was straw coloured. Microscopy showed inflammatory cell count of 4230 white blood cells/mm, with 91% neutrophils. She was treated as probable septic arthritis with intravenous (IV) flucloxacillin. After 48 hours on IV antibiotics, her CRP remained elevated, and she developed pyrexia. Blood and joint fluid cultures were negative. MRI scan confirmed active synovitis with features suggesting joint infection. On discussion with microbiology, oral doxycycline was added on day 3 to cover possible atypical organisms. After a further 4 days the swelling, range of movement, and pain in her elbow had significantly improved. She was discharged home with oral flucloxacillin and doxycycline. On day 16 M. hominis was identified from the Bacterial Identification Services Colindale, by partial sequencing of 16s rDNA from the joint aspirate. She was therefore advised to continue with oral doxycycline for a total of 6 weeks. Results After treatment, her CRP, ESR and range of movement returned to normal. Conclusion This case highlights the potential pathogenicity of M. hominis in immunocompromised patients. A literature review found 35 published case reports of septic arthritis by M. hominis, with two occurring in patients with SLE. Approximately 70% of the affected cases were in immunocompromised patients who had a poor response to empirical antibiotic therapy. However, identification of M. hominis on joint aspiration and subsequent treatment with appropriate antibiotics resulted in good outcomes for all published cases. Disclosure R.M. Hum: None. H. Iftikhar: None. E.Y. Tang: None. I. Bruce: None. P. Ho: None.

Background/Aims Anti-synthetase syndrome (ASS) represents a distinct entity within myositis spectrum disorders; however, correct classification of patients with anti-tRNA synthetase autoantibodies and skin manifestations akin to dermatomyositis (DM) remains uncertain. Our aim was to compare clinical characteristics, skin involvement, and malignancy, between patients with ASS and DM, classified by disease-specific autoantibodies. Methods Data from 05/2009-03/2016 from 9 countries from the prospective, myositis EuroMyositis registry were downloaded. Those with anti-tRNA synthetase autoantibodies (Jo-1/PL-7/PL-12/OJ/EJ/KS) were classified as ASS, and those with Mi-2/TIF1-γ/NXP2/SAE/MDA5 autoantibodies as DM. Clinical phenotypes including malignancies (except skin malignancies) were tabulated. Characteristics of patients with skin involvement (excluding mechanic’s hands and Raynaud’s phenomenon) were compared using Fisher’s exact test with Bonferroni corrected p-values. Results Of 3,067 patients, 2,028 had autoantibody profiling results (66.1%), of which 783 (38.6%) were positive for at least one of the autoantibodies being considered. Five patients with dual autoantibody specificities were excluded. Of the remaining 778, 320 (41.1%) were classified as DM, and 458 (58.9%) as ASS. Median age at diagnosis was 48.2 years (interquartile range [IQR] 37.5 to 57.8) in the DM cohort and 49 (IQR 38.3 to 62.2) in the ASS cohort. Skin involvement was present in 277 (86.6%) DM patients (DM skin) vs 204 (44.5%) ASS patients (ASS skin) (pcorr Conclusion Patients with ASS have frequent skin involvement but also a distinct clinical phenotype compared to DM. These findings may inform the development of future classification criteria for ASS. Disclosure R.M. Hum: None. J.B. Lilleker: None. J.A. Lamb: None. W.E. Ollier: None. G. Wang: None. L.R. Wedderburn: None. L.P. Diederichsen: None. J. Schmidt: None. P. Oakley: None. O. Benveniste: None. M.G. Danieli: None. K. Danko: None. N.T.P. Thuy: None. M.V.D. Mercado: None. H. Andersson: None. B.D. Paepe: None. J.L.D. Bleecker: None. B. Maurer: None. L.J. McCann: None. N. Pipitone: None. N. McHugh: None. P. New: None. J. Vencovsky: None. I.E. Lundberg: None. H. Chinoy: None.

Umbilical cord blood (UCB) is the preferred donor cell source for children with Hurler syndrome undergoing transplant, and its use has been associated with improved “engrafted survival” rates. However, as in other pediatric recipients of UCB transplants for nonmalignant disease, immune-mediated cytopenia (IMC) is a significant complication. This article describes 8 episodes of IMC in 36 patients with Hurler syndrome undergoing UCB transplant. The incidence of IMC was increased in those with a higher preconditioning absolute lymphocyte count and in those conditioned with fludarabine-containing regimens rather than cyclophosphamide, and it included red cell alloantibodies directed at cord blood group antigens that are novel to the recipient. In several cases, IMC was a precursor to immune-mediated complete graft rejection. We describe IMC as part of a spectrum of graft rejection by a residual competent host immune system and a forme fruste of complete graft rejection.

Summary Background Faecal shedding of adenovirus following allogeneic haematopoietic stem-cell transplantation (HSCT) is an early sign of loss of immune control over adenovirus, but there is no consensus on the role of monitoring of faecal adenoviral load by serial testing. We investigated whether serial faecal PCR monitoring could predict the risk of adenoviraemia and survival outcomes after HSCT. Methods We did a retrospective cohort study at the Royal Manchester Children's Hospital, Manchester, UK, of patients who had received their first allogeneic HSCT between Feb 1, 2003, and Sept 1, 2016, and adenovirus infection recorded in their medical records. We excluded patients who had received second or third transplants or autologous HSCT transplants. We obtained characteristics of patients and transplants, including mortality and adenoviral reactivation, from medical records and the hospital database. All patients had blood samples tested weekly for adenovirus by PCR until immunosuppression was stopped and CD3 T-cell count recovered to greater than 0·3 × 10 9 /L. Faecal PCR was done before transplantation in all patients, and after transplantation in patients who had diarrhoea, at the onset of symptoms and weekly thereafter until diarrhoea resolved. We analysed all samples available before and after HSCT. We did subgroup analyses for patients undergoing HSCT for cancer versus non-malignant conditions. We also assessed whether 5 log 10 copies per g faeces was a suitable predictive threshold for adenoviraemia. Findings We included 341 patients who had undergone a first allogeneic HSCT (median age 4·6 years, IQR 1·5–8·0, range 0–20·0). After HSCT, PCR was done in 4116 faecal samples from 293 (86%) patients who had diarrhoea and in 10 649 blood samples from 341 patients. Follow-up ended on July 14, 2017. 173 (59%) of 293 patients had adenovirus in faecal samples and 63 (18%) of 341 had adenovirus in blood samples. Maximum faecal viral load before adenoviraemia correlated significantly with maximum blood viral load ( r =0·51, 95% CI 0·38–0·61, p 10 copies per g faeces was predictive of adenoviraemia (odds ratio 10·2, 95% CI 4·9–21·6, p vs 7·8%, 3·8–13·7 in those with positive faeces only), but was significantly increased in patients who developed adenoviraemia (27·0%, 95% CI 16·7–38·4, p Interpretation We identified a threshold faecal viral load that can predict the risk of adenoviraemia. Our findings support proliferation of adenovirus in the gastrointestinal tract before viraemia develops. Faecal PCR is suitable for early detection of children and young adults at risk of adenoviraemia, and its use might help reduce non-relapse mortality in allogeneic HSCT recipients. Funding None.

Background: Hurler's syndrome is the most severe phenotype of Mucopolysaccharidosis 1 (MPS1H) with severe deficiency of the lysosomal enzyme alpha-L-iduronidase causing heparan and dermatan sulfate accumulation, CNS and somatic manifestations and premature death. Haematopoeitic Stem Cell Transplant (HSCT) alters the disease phenotype and prevents early death, and is standard of care in this condition. The use of an established 'donor hierarchy' recommending Unrelated Cord Blood Transplantation (UCBT) in the absence of a HLA-matched, non-carrier sibling, has resulted in improved engrafted and surviving rates and better post-enzyme levels with improved somatic and CNS clinical outcomes. However, UCBT for malignant and non-malignant conditions has led to high rates of post-transplant autoimmune disease, most frequently Autoimmune Cytopenia (AIC). We report a large cohort of MPS1H patients receiving busulfan-based UCBT and show that AIC is a frequently encountered complication of treatment with significant associated morbidity and we identify important risk factors for its occurrence. Methods: This was a retrospective observational study of patients undergoing first UCBT for Hurler's Syndrome at the Royal Manchester Children's Hospital between 30th September 2004 and 15th March 2018. An episode of AIC was defined as an episode of single or multi-lineage cytopenia occurring post-engraftment, confirmed by the presence of antibodies or diagnosed on the basis of clinical, biochemical and pathologic features. All patients received pK targeted busulfan to achieve myeloablative levels between 80-90 mg/L x hr. Conditioning between 2004 and May 2010 was with Busulfan and Cyclophosphamide (BuCy), and Fludarabine and Busulfan (FluBu) thereafter based on the reported equivocal efficacy and favourable toxicity profile of FluBu conditioning. All patients received serotherapy with Anti-Thymocyte Globulin (ATG) 10mg/kg for In Vivo T-Cell depletion. Timing of ATG was either distal (day -4 to -1) or proximal (day - 9 to -6) in accordance with international consensus at the time. Variables assessed in statistical analysis were conditioning drugs, ATG timing, Absolute Lymphocyte Count pre-conditioning, age-at-transplant, Graft-versus-Host Disease (GVHD) and Total Nucleated Cell dose. Results and Discussion: Thirty-six patients underwent first UCBT for Hurler's Syndrome. There were 8 episodes of AIC (22%), with median onset post-UCBT of 66 days (range 22-236 days). The median number of therapies required was 4 (range 0-8), with duration of illness ranging from 10 to 215 days. There were no deaths, though there were 2 episodes of life-threatening bleeding. Absolute Lymphocyte Count pre-conditioning (p=0.004), FluBu conditioning (p=0.03) and use of proximal-ATG (p=0.016) were significant risk factors for AIC in univariate analysis(see figure 1). Absolute Lymphocyte Count pre-conditioning was the most significant predictor in multivariable analysis (AOR 5.796, CI 0.921-36.474). This confirms that AIC is a frequent, serious but survivable complication of UCBT for Hurler's Syndrome. This data indicates that the balance between recipient immunity and graft immunity impacts AIC risk and severity, mandating a larger international review of registry data to define the frequency of AIC in this population, and an analysis of the risk factors that predispose to it. By better defining these risk factors, we can identify patients in whom conditioning might be altered to reduce risk. Figure 1. Univariate analysis of variables predicting an episode of Autoimmune Cytopenia. ALC (p=0.004), ATG timing (0.016) and Conditioning drugs (p=0.032) were significant risk factors. GVHD= Graft-versus-Host Disease ATG= Anti-Thymocyte Globulin Disclosures Wynn: Orchard SAB: Membership on an entity's Board of Directors or advisory committees; Orchard Therapeutics: Equity Ownership; Chimerix: Research Funding; Genzyme: Honoraria; Bluebird Bio: Consultancy; Orchard Therapeutics: Consultancy; Chimerix: Consultancy.