Genome-wide association studies (GWAS) have uncovered the genetic basis behind many diseases and conditions. However, most of these genetic loci affect regulatory regions, making the interpretation challenging. Chromatin conformation has a fundamental role in gene regulation and is frequently used to associate potential target genes to regulatory regions. However, previous studies mostly used small sample sizes and immortalized cell lines instead of primary cells. Here we present the most extensive dataset of chromatin conformation with matching gene expression and chromatin accessibility from primary CD4+ and CD8+ T cells to date, isolated from psoriatic arthritis patients and healthy controls. We generated 108 Hi-C libraries (49 billion reads), 128 RNA-seq libraries and 126 ATAC-seq libraries. These data enhance our understanding of the mechanisms by which GWAS variants impact gene regulation, revealing how genetic variation alters chromatin accessibility and structure in primary cells at an unprecedented scale. We refine the mapping of GWAS loci to implicated regulatory elements, such as CTCF binding sites and other enhancer elements, aiding gene assignment. We uncover BCL2L11 as the probable causal gene within the rheumatoid arthritis (RA) locus rs13396472, despite the GWAS variants’ intronic positioning relative to ACOXL, and we identify mechanisms involving SESN3 dysregulation in the RA locus rs4409785. Given these genes’ significant role in T cell development and maturation, our work deepens our comprehension of autoimmune disease pathogenesis, suggesting potential treatment targets. In addition, our dataset provides a valuable resource for the investigation of immune-mediated diseases and gene regulatory mechanisms.

Sleep disturbance has been associated with chronic widespread pain (CWP), but their causal relationship remains unclear. We aimed to examine the causal relationship and direction between CWP and sleep traits, namely insomnia, sleep duration and chronotype, using Mendelian Randomization. We used genetic association data from 0.5 million individuals and up to 1.8 million controls from the UK Biobank (UKB). All traits were defined predominantly by self-report. Short sleep duration was defined as average ≤6 hours per 24 hours. Chronotype refers to the inclination to sleep at certain times where some wake and go to bed early (‘morning’ person), and others wake and go to sleep later (‘evening’ person). To permit use of the largest available genetic association data, we used the Causal Analysis Using Summary Effect estimates (CAUSE) method, which allows for sample overlap. Insomnia (OR 1.009, 95

Background: The global obesity epidemic presents a major challenge to chronic disease management. Obesity is a core component of metabolic syndrome and related comorbidities. Although studies have described the prevalence of metabolic syndrome in individual inflammatory arthritides, few have compared their prevalence in parallel. Objectives: To describe the prevalence of metabolic syndrome in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Methods: This was an observational cross-sectional study using data from the UK Biobank, which is a study of over 500,000 adults between the ages of 40 and 69 who were recruited between 2006 and 2010. The participants with RA, PsA and AS were identified using ICD 10 codes from hospital admission data and Read codes from primary care, as well as by self-report. Metabolic syndrome was defined as per the widely adopted National Cholesterol Education Programme (NCEP) Adult Treatment Panel III (ATP III) criteria, which necessitates the fulfilment of at least three out of five specified criteria for diagnosis. These include: 1) Blood pressure >130/85 (we utilised baseline blood pressure measurements, a self-reported or coded diagnosis of hypertension, or the use of antihypertensives). 2) Fasting blood sugar ≥ 5.6 mmol/l (we utilised baseline blood glucose measurements, a self-reported or coded diagnosis of Type 2 Diabetes Mellitus, or the use of diabetes medications (excluding insulin). 3) Waist circumference ≥ 102 cm in men or 88 cm in women. 4) High-density lipoprotein (HDL) cholesterol <1 mmol/l in men or 1.293 mmol/l in women or use of a lipid-lowering medication. 5) Triglyceride levels ≥ 1.693 mmol/l (we utilised baseline blood triglyceride levels). Results: The study included a total of 502,422 participants with a mean (SD) age of 57 (8.1) years; comprising 229,088 (45.6%) males and 273,334 (54.4%) females. Among them, 3220 (0.6%) had Rheumatoid arthritis (RA), 1067 (0.2%) had Psoriatic Arthritis (PsA), 1483 (0.3%) had Ankylosing Spondylitis (AS) and the remaining 496652 (98.9%) without the three in inflammatory arthritides served as controls. Participants with RA, PsA and AS exhibited a higher prevalence of metabolic syndrome compared to the control group. Specifically, 1342 (41.7%) of those with RA, 432 (40.5%) with PsA, and 535 (36.1%) with AS had metabolic syndrome, compared to 152380 (30.7%) in the control group. Individuals in the RA, PsA and AS groups consistently exceeded controls in the proportions meeting each of the five metabolic syndrome criteria. Notably, RA group consistently surpassed the PsA and AS except for the triglyceride criterion. The most substantial disparity was observed in the proportions of individuals meeting the low HDL cholesterol criteria; 1385 (44.5%) in RA, 378 (37.7%) in PsA, 521 (37.8%) in AS, versus 147490 (31.4%) in the control group. Additionally, a significant difference was noted in the proportions of participants attaining the high glucose criteria: 702 (21.8%) in RA, 205 (19.2%) in PsA, 248 (16.7%) in AS, versus 75754 (15.3%) in the control group. On top of this, a much larger proportion of participants in the RA and PsA groups were on antihypertensive medication; 1206 (68.8%) in RA and 329 (47.1%) in PsA versus 448 (41.0%) in AS and 109417 (38.8%) in the control group. In a similar way, those with the inflammatory arthritides under investigation were more likely to have a previous diagnosis of hypertension: 1240 (38.7%) in RA, 399 (37.5%) in PsA, 520 (35.2%) in AS compared to 136744 (27.7%) in the control group. Conclusion: The findings of this cross-sectional study show that metabolic syndrome is highly prevalent even among individuals of the UK Biobank who are recognised to be healthier than the general population. Metabolic syndrome was more prevalent among people with RA, PsA and AS compared to those without these inflammatory arthritides, with RA having the highest prevalence, then PsA and AS. These results highlight the importance of identifying and managing metabolic syndrome among people with inflammatory arthritis. Acknowledgements: NIL. Disclosure of Interests: Kira Rogers: None declared, Joshua Southworth: None declared, Ryan Malcolm Hum: None declared, Pauline Ho Abbvie, Novartis, Janssen, Sizheng Steven Zhao UCB, Novartis, UCB

Abstract Background/Aims The Psoriatic Arthritis Impact of Disease 12-item questionnaire (PsAID-12) was developed and validated to improve assessment of disease activity from the patient’s perspective. Several patient-reported outcome measures (PROMs) are relevant to PsA but completing several questionnaires at each clinic visit creates a time and administrative burden for patients and clinicians. Furthermore, the Minimal Disease Activity (MDA) for assessing disease activity in PsA requires the Health Assessment Questionnaire (HAQ) to be collected; however, a Canadian study found that PsAID-12 can replace HAQ in the MDA using a cut-off of < 3.7. A previous study also found sex-specific differences in PsAID-12 scores, with scores being higher in females. The aim of this study was to assess whether PsAID-12 correlates well and could replace other PROMs in clinical practice, and to validate previously published findings related to the use of PsAID-12 instead of HAQ in determining MDA, and sex-specific differences in PsAID-12 scores. Methods Clinical data were collected from 75 consecutive patients attending a PsA clinic in a tertiary centre at their first review in 2023. Clinical characteristics, PROMs, examination findings, and measures of disease activity were recorded. Correlation with PsAID-12 was assessed using Spearman’s rank correlation coefficient. Sex-specific differences were assessed using Mann-Whitney U tests. Bonferroni correction was used to adjust for multiple comparisons. Results PsAID-12 scores were significantly correlated with all PROMs, and with composite measures of disease activity (DAPSA, MDA), but not with clinical measures of disease activity (TJC, SJC, PASI, BSA), or acute-phase reactants (CRP, ESR). PsAID-12 scores were not affected by age or disease duration. There was no sex-dependent difference in PsAID-12 scores; however, female patients had significantly higher HAQ and HAD scores. MDA scores using PsAID-12 correlated significantly with MDA scores using HAQ. Conclusion PsAID-12 is a suitable replacement for other PROMs in clinical practice, and for HAQ when determining MDA status to reduce the time and administrative burden on patients and clinicians, and to facilitate monitoring of disease activity in patients with PsA regardless of age or disease duration. Contrary to previous studies, there were no sex-dependent differences in PsAID-12 scores. Disclosure R.M. Hum: None. K. Hasanein: None. L.T. Hao: None. J.C. Williams: None. A. Cheung: None. A. Adhikarla: None. A. Choyce: None. A. Newton: None. C. Clegg: None. A. Barton: None. P. Ho: None.

Psoriatic arthritis (PsA) is an inflammatory joint and entheseal disease associated with significant personal and public health burden. PsA has a prevalence of up to 1%, affecting ~20% of people suffering with psoriasis. PsA is frequently accompanied by metabolic syndrome (MetS), and both conditions are characterised by a chronic pro-inflammatory state, with several key cytokines in PsA (interleukin (IL)-17 and IL-23) also elevated in those with MetS. This narrative review aims to provide an update on MetS in PsA, focusing on its prevalence, pathogenesis, prognosis, treatment interactions and future therapeutic options. MetS is particularly prevalent in PsA compared to other inflammatory arthritides. Cohort studies indicate a higher risk of PsA in individuals with obesity, while Mendelian randomization studies link childhood obesity, insulin resistance, and dyslipidaemia to PsA. Weight loss interventions have been shown to reduce disease activity in PsA. Additionally, MetS negatively impacts the efficacy of tumour necrosis factor inhibitor (TNFi) drugs in treating PsA. Drugs given for PsA may also affect the conditions constituting MetS. Leflunomide has been shown to reduce body weight but also increase blood pressure. TNFi drugs lead to weight gain but reduce cardiovascular risk. Janus kinase inhibitors increase lipid levels and cardiovascular risk among high-risk groups. Anti-IL-17 and anti-IL-12/IL-23 drugs may cause a short-term increase in cardiovascular risk, although the long-term effects have yet to be established. Weight loss represents an unexplored avenue for disease modification in PsA, alongside a plethora of general health benefits. Dietary and exercise modifications are the cornerstone of weight management but vary substantially across individuals. Novel therapies to treat weight loss, such as glucagon-like peptide 1 agonists and sodium–glucose cotransporter 2 inhibitors, may prove useful alongside disease-modifying therapies for those with PsA and MetS and should be investigated as potential therapeutic adjuncts.

Background: The Psoriatic Arthritis Impact of Disease 12-item questionnaire (PsAID-12) was developed and validated in 474 patients by a EULAR Taskforce in 2014 to allow better assessment of disease activity and symptom burden from the patient’s perspective in PsA for clinical practice. A variety of patient reported outcome measures (PROMs) are relevant to PsA but completing several PROM questionnaires at each clinic visit creates a time and administrative burden for patients and clinicians. In addition, although the Minimal Disease Activity (MDA) metric for assessing disease activity in PsA requires the Health Assessment Questionnaire (HAQ) PROM to be collected, a Canadian study found that the PsAID-12 could replace the HAQ in the MDA using a PsAID-12 cut-off of <3.7.[1] A previous study also found sex-specific differences in PsAID-12 scores, with scores being higher in females.[2] Objectives: The aim of this study was to assess whether the PsAID-12 correlates well and could therefore replace other PROMs in clinical practice, and to validate previously published findings related to the use of PsAID-12 as a replacement for the HAQ in the MDA, and sex-specific differences in PsAID-12 scores. Methods: Routine clinical data was collected from 91 consecutive patients attending a weekly PsA clinic in a tertiary centre at their first review in 2023. Clinical characteristics including age, sex, disease duration, BMI, smoking, peripheral/axial/eye/GI involvement, HLA-B27, CCP and RF status were collected. PROMs including the PsAID-12, HAQ, Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HAD), and EQ-5D were assessed. Clinical examination findings including 68-tender joint count, 66-swollen joint count, Leeds Enthesitis Index, Dactylitic joints, Nail Involvement, Psoriasis Area and Severity Index (PASI), and body surface area (BSA) were recorded. Measures of disease activity including ESR, CRP, Disease Activity in PsA (DAPSA), and the MDA were recorded.Correlation of PsAID-12 with other PROMs, clinical findings, measures of disease activity, and correlation of the MDA using HAQ or PsAID-12 were assessed using Spearman’s rank correlation coefficient. Sex-specific differences were assessed using Mann-Whitney U tests. Bonferroni correction was used to adjust for multiple comparisons. Results: PsAID-12 scores were significantly correlated with all PROMs, and with composite measures of disease activity (DAPSA and MDA) and clinical measures of disease activity (TJC, SJC, PASI, BSA), but not with acute-phase reactants (CRP, ESR). There was no significant correlation between PsAID-12 scores and age or disease duration. There was no significant sex-dependent difference in PsAID-12 scores; however, female patients had significantly higher HAQ and HAD-depression scores. MDA scores using PsAID-12 correlated significantly with MDA scores using HAQ (rho = 0.99, p<0.0001). Conclusion: PsAID-12 is a suitable replacement for other PROMs in clinical practice to reduce the time and administrative burden on patients and clinicians, and to facilitate monitoring of disease activity in patients with PsA regardless of age or disease duration. We found PsAID-12 is a suitable replacement for the HAQ when determining MDA status, and that contrary to previous studies there were no sex-dependent differences in PsAID-12 scores. REFERENCES: [1] Johnson K, Ye JY, Chandran V, Gladman DD. A novel role for the psoriatic arthritis impact of disease (PsAID) questionnaire. Semin Arthritis Rheum. 2019;49(2):241-5.[2] Lubrano E, Scriffignano S, Fatica M, Triggianese P, Conigliaro P, Perrotta FM, et al. Psoriatic Arthritis in Males and Females: Differences and Similarities. Rheumatol Ther. 2023;10(3):589-99.Table 1. Cohort characteristicsTable 2. Measures of disease activity with sex-dependent differences and Spearman’s rank correlation coefficients for measures of disease activity compared with PsAID-12 Acknowledgements: NIL. Disclosure of Interests: None declared.

Background/Aims The Psoriatic Arthritis Impact of Disease 12-item questionnaire (PsAID-12) was developed and validated to improve assessment of disease activity from the patient's perspective. Several patient-reported outcome measures (PROMs) are relevant to PsA but completing several questionnaires at each clinic visit creates a time and administrative burden for patients and clinicians. Furthermore, the Minimal Disease Activity (MDA) for assessing disease activity in PsA requires the Health Assessment Questionnaire (HAQ) to be collected; however, a Canadian study found that PsAID-12 can replace HAQ in the MDA using a cut-off of<3.7. A previous study also found sex-specific differences in PsAID-12 scores, with scores being higher in females. The aim of this study was to assess whether PsAID-12 correlates well and could replace other PROMs in clinical practice, and to validate previously published findings related to the use of PsAID-12 instead of HAQ in determining MDA, and sex-specific differences in PsAID-12 scores. Methods Clinical data were collected from 75 consecutive patients attending a PsA clinic in a tertiary centre at their first review in 2023. Clinical characteristics, PROMs, examination findings, and measures of disease activity were recorded. Correlation with PsAID-12 was assessed using Spearman's rank correlation coefficient. Sex-specific differences were assessed using Mann-Whitney U tests. Bonferroni correction was used to adjust for multiple comparisons. Results PsAID-12 scores were significantly correlated with all PROMs, and with composite measures of disease activity (DAPSA, MDA), but not with clinical measures of disease activity (TJC, SJC, PASI, BSA), or acute-phase reactants (CRP, ESR). PsAID-12 scores were not affected by age or disease duration. There was no sex-dependent difference in PsAID-12 scores; however, female patients had significantly higher HAQ and HAD scores. MDA scores using PsAID-12 correlated significantly with MDA scores using HAQ. Conclusion PsAID-12 is a suitable replacement for other PROMs in clinical practice, and for HAQ when determining MDA status to reduce the time and administrative burden on patients and clinicians, and to facilitate monitoring of disease activity in patients with PsA regardless of age or disease duration. Contrary to previous studies, there were no sex-dependent differences in PsAID-12 scores. Disclosure R.M. Hum: None. K. Hasanein: None. L.T. Hao: None. J.C. Williams: None. A. Cheung: None. A. Adhikarla: None. A. Choyce: None. A. Newton: None. C. Clegg: None. A. Barton: None. P. Ho: None.

Background: Polygenic risk scores to aid diagnosis have been developed and applied in research settings and limited real-world settings. For example, the G-PROB tool has been shown to perform well in excluding certain diagnoses, when used in cohorts of patients enriched for inflammatory arthritis. However, the performance of these tools can be affected by the prevalence of the conditions and, therefore, it is important to obtain accurate prevalence estimates of inflammatory arthritis diagnoses in real-world, early arthritis clinics.[1, 2] Objectives: The aim of this study was to determine the prevalence of rheumatic diseases in a real-world cohort of patients newly referred to a UK tertiary early inflammatory arthritis (EIA) clinic over 1 year and to determine the proportion of patients who are "misdiagnosed" on first presentation and have their diagnosis revised at follow-up. Methods: Patients were referred to the EIA clinic by primary care if they had clinical symptoms and physical examination findings suggestive of inflammatory arthritis. In EIA clinic, patients were seen by a rheumatologist, an initial diagnosis was made, and treatment was initiated if appropriate. Patients were followed up in EIA clinic and a final diagnosis was made. Routine clinical data was collected from electronic patient records and tabulated. Clinical diagnoses were grouped into six categories (rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondylarthritis (SpA), systemic lupus erythematosus (SLE), and other) to enable comparisons with previously published cohorts in which polygenic risk score approaches (G-PROB platform) have been applied. Results: Over 12-months, 164 new patients were seen in the EIA clinic, where the mean age was 47 (SD 17), 64% (n=105) were of female sex, 65% (n=90) were of non-white ethnicity, and 42% (n=69) were current or ex-smokers. The vast majority had peripheral joint symptoms (n=154, 94%), whilst 23% (n=37) had axial symptoms, 15% (n=25) had psoriasis, 5% (n=8) had inflammatory bowel disease, and 4% (n=6) had uveitis. In terms of treatment, 9% (n=16) of patients received corticosteroids, and 12% (n=19) were started on a DMARD. In terms of laboratory results, 9% (n=14) were ACPA-positive, 17% (n=28) were RF-positive, and mean ESR and CRP was 17 (SD 17) and 10 (SD 21) respectively. Proportions of clinical diagnoses were different in the EIA cohort compared to previously published cohorts; non-inflammatory conditions such as chronic pain syndromes and simple musculoskeletal pain were more frequently diagnosed and prevalent in the EIA clinic. However, of the rheumatic diseases, RA was the most prevalent in all cohorts. (Table 1) Seventeen patients (10%) had their diagnosis changed at follow-up in EIA clinic: 7 patients initially diagnosed with a chronic pain syndrome had their diagnosis changed to RA (n=2), PsA (n=1), Gout (n=2), reactive arthritis (n=1), and undifferentiated connective tissue disease (UCTD) (n=1); 4 patients diagnosed with RA changed to PsA (n=1), dermatomyositis (n=1), polymyalgia rheumatica (n=1), UCTD (n=1); 1 patient with PsA changed to Dupilumab-induced arthritis; 2 patients with gout changed to RA and PsA; 2 patients with primary Raynaud's changed to RA and UCTD; and 1 patient with UCTD changed to sarcoidosis. Conclusion: Disease prevalence is context-specific, where prevalence estimates in the intended setting should be determined prior to implementation of prediction tools such as polygenic risk scores. In contrast to observational studies and registries, in this real-world cohort we significantly found higher prevalence of non-inflammatory diseases such as chronic pain syndromes. Ten percent of patients were "misdiagnosed" and may have benefitted from novel diagnostic tools such as G-PROB to aid earlier and more accurate diagnosis. REFERENCES: [1] Knevel R et al. Using genetics to prioritize diagnoses for rheumatology outpatients with inflammatory arthritis. Sci Transl Med. 2020. [2] Hum RM et al. Using polygenic risk scores to aid diagnosis of patients with early inflammatory arthritis: results from the Norfolk Arthritis Register. Arthritis Rheumatol. 2023. Table 1. Prevalence of rheumatic diseases Acknowledgements: Muhammad Saad Aleem & Zina Mobarak have contributed equally and are regarded as joint first authors. Pauline Ho and Ryan Malcolm Hum contributed equally and are regarded as joint last authors. Disclosure of Interests: None declared.

Objectives Up to 40% of PsA patients experience first-line tumour necrosis factor inhibitors (TNF-i) failure. Lower serum drug levels (SDL) have been associated with lower response in autoimmune conditions. This study aimed to: (i) establish the relationship between adalimumab (ADL) and etanercept (ETN) SDL and 3-month response; and (ii) identify optimal non-trough SDL thresholds in PsA.Methods PsA patients commencing ADL or ETN were recruited to the UK observational study OUTPASS. Patients were seen pre-TNF-i and at 3 months when response was measured, and non-trough serum samples collected. Response was defined according to the PsARC or EULAR criteria. Descriptive statistics and concentration-effect curves established differences in SDL based on response. Receiver operating characteristic curves and regression identified optimal SDL thresholds.Results PsA ETN (n = 97) PsARC and EULAR good responders had significantly higher 3-month SDL compared to non-responders (P = 0.006 and P = 0.020, respectively). Non-trough 3-month ETN SDL discriminated PsARC responders from non-responders (AUC = 0.70), with a threshold of 1.8 mu g/ml being 63% specific and 69% sensitive. EULAR good and non-/moderate responders were discriminated with an AUC of 0.65 with a threshold of 2.0 mu g/ml being 57% specific and 69% sensitive. ADL prescribed (n = 104) EULAR good responders had significantly higher 3-month SDL (P = 0.049). Non-trough 3-month ADL SDL discriminated EULAR good and non-/moderate responders (AUC = 0.63) with a threshold of 3.6 mu g/ml being 48% specific and 81% sensitive.Conclusion Higher 3-month SDL were detected in responders. Interventions to optimise SDL may improve treatment response earlier. This study suggests 3-month SDL thresholds which may be useful in clinical practice to optimize treatment response.

Purpose: Psoriatic arthritis (PsA) is a chronic autoimmune disease that causes a variety of musculoskeletal abnormalities. Musculoskeletal ultrasound in PsA is becoming increasingly popular, both in clinical practice and research. This narrative reviews recent literature on the utility of ultrasound in PsA. Methods: A search of PubMed was used to identify publications written in English, with titles containing the term psoriatic arthritis and either ultrasound, ultrasonography, or sonographic. A total of 178 publications were identified; those that were not relevant (n = 59), were not original research (n = 45), or that had small ( < 30) sample sizes (n = 34) were excluded, leaving 40 studies for review of the use of ultrasound in various aspects of PsA. Publications with similar findings were grouped into seven domains: (1) the use of ultrasound findings compared to clinical assessment; (2) the use of ultrasound in the assessment of enthesitis; (3) the use of ultrasound in the assessment of nails; (4) the use of ultrasound as a screening tool in patients with psoriasis at risk for PsA; (5) the use of ultrasound in differentiating PsA from other similar conditions; (6) the use of ultrasound as a measure of disease activity; and (7) the use of ultrasound compared to MRI. Findings: In recent studies, ultrasound measures of inflammation tended to agree with objective clinical findings of disease, such as swollen joint counts, while being less influenced by subjective measures, such as pain. Ultrasound has utility in the assessment of enthesitis and psoriatic nail disease in PsA, and as an overall measure of disease activity. Ultrasound-based outcomes measures have been used in observational studies and in clinical trials involving PsA, and may have utility as a measure of treatment response. The findings from recent studies suggest that ultrasound may have utility in improving the accuracy and precision of screening programs designed to identify subclinical PsA in cohorts of patients with psoriasis; however, cost-efficacy remains to be determined. Beyond screening, ultrasound may have utility in the diagnosis of PsA in patients with suspected inflammatory arthritis, and ultrasound measures of inflammation agree with MRI measures of inflammation, meaning that incorporating ultrasound into clinical practice might help to overcome the barriers associated with MRI. Implications: As ultrasound technology continues to advance, and associated costs decrease, it is likely that ultrasound will become more integrated into the clinical journeys of patients with PsA.

Abstract 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 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.

Abstract Background/Aims Recent translational advances in genetics report the ability to accurately predict the diagnosis of patients presenting with synovitis, providing potential to accelerate treatment and improve patient outcomes. One tool is G-PROB, which uses genetic information to calculate conditional probabilities, known as G-probabilities ranging from 0 to 100%, for defined diseases. In the original study, G-PROB was configured to discriminate between patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and “other rheumatological diseases” using reported bias-adjusted odds ratios from 250 known single nucleotide polymorphisms and human leukocyte antigen variants of uncorrelated risk variants. The original study tested G-PROB on 243 patients with synovitis. Our aim was to assess whether G-PROB could aid diagnosis using data from the Norfolk Arthritis Register (NOAR), a large observational cohort of patients with early inflammatory arthritis. Methods Genotypes, and clinician diagnosis were obtained from NOAR. The same prevalence settings and risk variants as the original study were used. Six G-probabilities each corresponding to one disease were created for each patient and performance was assessed using linear regression without intercept, negative and positive predictive values (NPV, PPV), and receiver-operator-curve (ROC) analysis. Results From NOAR, 2031 genotyped patients were identified and underwent case note review to determine the clinician diagnosis. Clinician diagnoses included RA (n = 767), PsA (n = 106), SpA (n = 15), SLE (n = 14), gout (n = 5), and “other” (n = 65). For n = 1059, case notes were not available resulting in exclusion. The mean G-probability was 41% for those which corresponded to clinician-defined disease, which was significantly higher compared to 12% for those that did not (95%CI -0.30 to -0.28). As reported in the original study, G-probabilities were concordant with real disease status (β regression coefficient of 1.03 vs 0.99, where 1.00 is ideal). We found 42% of all G-probabilities were <5%, corresponding to a NPV of 99%, where it was possible to deprioritise >1 disease for 100% of patients, >2 diseases for 96% of patients, and >3 diseases for 69% of patients. We found 17.8% of patients had a single G-probability >50% corresponding to a PPV of 41%. This compared to 45% of patients, and PPV of 64% reported in the original study. Accuracy of G-probabilities to discriminate clinician-defined disease was similar in our cohort (AUC of 0.86 95% CI 0.84-0.87) compared to the original study (AUC 0.84 95% CI 0.81-0.86). In 57% of patients in our cohort, the disease with the highest G-probability corresponded to the clinician-defined disease compared to 53% in the original study. Conclusion We were able to replicate several findings of the original study in a large independent cohort including calibration, high NPV, but PPV was lower, suggesting that G-PROB is most valuable as a tool to rule out diagnoses. Disclosure R.M. Hum: None. S.D. Sharma: None. M. Stadler: None. N. Nair: None. S. Viatte: None. C. Yap: None. J.H. Humphreys: None. A. MacGregor: None. M. Yates: None. M. Soomro: None. S.M. Verstappen: None. P. Ho: None. A. Barton: None. J. Bowes: None.

Abstract 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.

Objective There is growing evidence that genetic data are of benefit in the rheumatology outpatient setting by aiding early diagnosis. A genetic probability tool (G‐PROB) has been developed to aid diagnosis has not yet been tested in a real‐world setting. Our aim was to assess whether G‐PROB could aid diagnosis in the rheumatology outpatient setting using data from the Norfolk Arthritis Register (NOAR), a prospective observational cohort of patients presenting with early inflammatory arthritis. Methods Genotypes and clinician diagnoses were obtained from patients from NOAR. Six G‐probabilities (0%–100%) were created for each patient based on known disease‐associated odds ratios of published genetic risk variants, each corresponding to one disease of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, spondyloarthropathy, gout, or “other diseases.” Performance of the G‐probabilities compared with clinician diagnosis was assessed. Results We tested G‐PROB on 1,047 patients. Calibration of G‐probabilities with clinician diagnosis was high, with regression coefficients of 1.047, where 1.00 is ideal. G‐probabilities discriminated clinician diagnosis with pooled areas under the curve (95% confidence interval) of 0.85 (0.84–0.86). G‐probabilities <5% corresponded to a negative predictive value of 96.0%, for which it was possible to suggest >2 unlikely diseases for 94% of patients and >3 for 53.7% of patients. G‐probabilities >50% corresponded to a positive predictive value of 70.4%. In 55.7% of patients, the disease with the highest G‐probability corresponded to clinician diagnosis. Conclusion G‐PROB converts complex genetic information into meaningful and interpretable conditional probabilities, which may be especially helpful at eliminating unlikely diagnoses in the rheumatology outpatient setting. image

Background Up to 28% of patients with anti-synthetase syndrome (AsyS) have dermatomyositis (DM)-type rashes. However, it is not clear whether ASyS patients with DM-type rashes should be treated similarly to patients with DM or classified as DM in a clinical trial setting. Furthermore, it is not known if presence of DM-type rashes confers an increased risk of DM-specific extramuscular manifestations, such as malignancy. Objectives To compare clinical characteristics, including the frequency of cutaneous, extramuscular features, and malignancy, between adults with ASyS and DM. Methods Using data from the MYONET registry, an adult cohort of DM patients with anti-Mi2/TIF1ɣ/NXP2/SAE/MDA5 autoantibodies, and an ASyS cohort of patients with anti-tRNA synthetase autoantibodies (anti-Jo1/PL7/PL12/OJ/EJ/KS), were identified. Patients with DM sine dermatitis and with dual autoantibody specificities were excluded. Sub-cohorts of ASyS patients with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules, violaceous rash, shawl sign, V sign, erythroderma, and/or periorbital rash). Results In total, 737 patients were included (DM, n=251; ASyS, n=486). Within the ASyS cohort, 34% (n=163) had DM-type skin involvement (ASyS-skin). A higher frequency of Raynaud's phenomenon differentiated ASyS-skin from DM (n=72, 44% vs n=34, 14%, p<0.01), whereas higher frequency of any of four DM-type rashes: heliotrope rash (n=155, 62% vs n=73, 45%), V sign (n=69, 28% vs n=22, 14%), periorbital rash (n=53, 21% vs n=27, 17%), and shawl sign (n=89, 36% vs n=15, 9%) differentiated DM from ASyS-skin (all p<0.01). Cancer-associated myositis (CAM) was more frequent in DM (17%) compared to ASyS (3%) and ASyS-skin (3%) cohorts (both p<0.01) (Table 1). Conclusion DM-type rashes are frequent in patients defined as having ASyS; however, certain clinical features differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance or investigation. These findings will help to inform future ASyS-based classification criteria. References [1]Hervier, Baptiste et al. “Hierarchical cluster and survival analyses of antisynthetase syndrome: phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity.” Autoimmunity reviews vol. 12,2 (2012): 210-7.[2]Lilleker, James B et al. “The EuroMyositis registry: an international collaborative tool to facilitate myositis research.” Annals of the rheumatic diseases vol. 77,1 (2018): 30-39. Acknowledgements This publication was supported by researchers at the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the United Kingdom (UK) National Health Service (NHS), the NIHR or the UK Department of Health. Disclosure of Interests Ryan Malcolm Hum: None declared, James B. Lilleker: None declared, Janine Lamb: None declared, Alexander Oldroyd: None declared, William Ollier: None declared, Guochun Wang: None declared, Chanakya Kodishala: None declared, Lucy Wedderburn: None declared, Louise Diederichsen Consultant of: Data safety monitoring board for Corbus Pharmaceuticals, Grant/research support from: Boehringer Ingelheim, Jens Schmidt: None declared, Maria Giovanna Danieli: None declared, Katalin Dankó: None declared, THI PHUONG THUY NGUYEN: None declared, Mónica Vázquez-Del Mercado Espinosa: None declared, Helena Andersson: None declared, Boel De Paepe: None declared, Jan De Bleecker: None declared, Britta Maurer Speakers bureau: Boehringer-Ingelheim, GSK, Novartis, Consultant of: Novartis, Boehringer Ingelheim, Janssen-Cilag, GSK, Grant/research support from: AbbVie, Protagen, Novartis, Medtalk, Pfizer, Roche, Actelion, Mepha, MSD, Liza McCann: None declared, Nicolo Pipitone: None declared, Robert Paul New: None declared, Niels Steen Krogh: None declared, Neil McHugh: None declared, Jiří Vencovský: None declared, Ingrid E. Lundberg Shareholder of: Roche, Novartis, Consultant of: Corbus Pharmaceuticals Inc, Advisory board for Corbus Pharmaceutical, EMD Serono, Argenx, Octapharma, Kezaar, Orphazyme, Pfizer, and Janssen., Grant/research support from: Astra Zeneca, Hector Chinoy: None declared.Table 1Clinical manifestations of diseaseDM (n=251)ASyS (n=486)ASyS-skin (n=163)ASyS-without-skin (n=323)DM vs ASyS Adjusted p-valueDM vs ASyS-skin Adjusted p-valueASyS-skin vs ASyS-without-skin Adjusted p-valueDM-type rashes n (%)Heliotrope Rash155 (62)73 (15)73 (45)0 (0)<0.01<0.01<0.01Gottron's Papules or Sign145 (58)110 (23)110 (68)0 (0)<0.010.66<0.01Violaceous Rash94 (38)51 (11)51 (31)0 (0)<0.010.23<0.01Erythroderma22 (9)9 (2)9 (6)0 (0)<0.010.11<0.01Periorbital Rash53 (21)27 (6)27 (17)0 (0)<0.010.04<0.01V Sign Rash69 (28)22 (5)22 (14)0 (0)<0.01<0.01<0.01Shawl Sign89 (36)15 (3)15 (9)0 (0)<0.01<0.01<0.01Extramuscular manifestations n (%)Periungual Erythema72 (29)75 (15)43 (26)32 (10)<0.010.045<0.01Calcinosis7 (3)9 (2)6 (4)3 (1)0.620.810.15Ulceration11 (4)5 (1)3 (2)2 (1)0.040.650.72Vasculitis4 (2)1 (0.2)0 (0)1 (0.3)0.0450.611Mechanic's Hands11 (4)142 (29)62 (38)80 (25)<0.01<0.01<0.01Raynaud's Phenomenon34 (14)178 (37)72 (44)106 (33)<0.01<0.01<0.01Arthritis29 (12)221 (46)77 (47)144 (45)<0.01<0.011Dysphagia72 (29)88 (18)35 (22)53 (16)<0.010.250.22Alopecia24 (10)26 (5)12 (7)14 (4)0.1710.21Interstitial Lung Disease28 (11)320 (66)100 (61)220 (68)<0.01<0.010.11Cardiac Involvement4 (2)30 (6)14 (9)16 (5)0.03<0.010.20CAM n (%)42 (17)16 (3)5 (3)11 (3)<0.01<0.010.90

Objectives: To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. Methods: Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1 gamma/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). Results: In total 1054 patients were included (DM, n = 405; ASyS, n = 649). In the ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P < 0.001), whereas higher frequency of any of four DM-type rashes-heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V-sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%)-differentiated DM from ASyS-DMskin (all P < 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both P < 0.001). Conclusion: DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

Abstract Introduction Idiopathic inflammatory myopathies (IIM) are a group of conditions characterised by immune-driven muscular inflammation, often in the presence of specific autoantibodies. NXP2 dermatomyositis is a subtype of IIM characterised by antibodies to nuclear matrix protein 2. NXP2 dermatomyositis is associated with calcinosis, especially in younger patients and with malignancy, especially in older patients. We report a case of NXP2 dermatomyositis in a female patient of West African descent presenting with a periorbital and upper back rash which was initially misdiagnosed as an allergic reaction. Images of darker skin are underrepresented in medical education around dermatomyositis. Case description A 49-year-old female office worker presented to A&E with a two-week history of arthralgia and fatigue. Over the past two days, she had also noticed the development of periorbital swelling and a rash on her eyelids and her upper back. On examination in A&E, the rash was considered minor and it was noted that she had difficulty taking off her coat due to pain in her arms. She was discharged home with a working diagnosis of an allergic reaction, with advice to see her GP if symptoms persisted. She was reviewed by her GP, who suspected a vasculitic rash. She was found to have a significantly raised ANCA-MPO antibody titre and was referred to the acute medical take where she was seen urgently by rheumatology on-call. On assessment, she was noted to have pain and morning stiffness in her hands and wrists, with swollen DIPJ, MCPJ and wrists on examination. On assessment by a rheumatologist aware of the skin manifestations of dermatomyositis, she was also noted to have a heliotrope rash, shawl sign, periungual erythema, and a V sign rash and was suspected to have dermatomyositis. Her CK was raised at 3000, and she was found to have NXP2 autoantibodies which confirmed the diagnosis. She was started on hydroxychloroquine whilst an MR scan of her arms and legs was organised, which revealed evidence of myositis in the proximal muscles. Following MR scanning, she was started on high dose corticosteroids. Azathioprine was subsequently initiated as a steroid sparing agent, but was not tolerated due to nausea and so she was switched to subcutaneous methotrexate. Her CK has now normalised, and her skin lesions are healing. Discussion One of the key issues highlighted by this case is the lack of awareness of rashes associated with dermatomyositis generally, and especially in diverse skin types. We suspect this is because of a lack of education and exposure to skin rashes in diverse skin types, especially in highly melanated skin types. On her initial assessment in A&E, her rash was misdiagnosed as an allergic reaction. We suspect a lack of familiarity with skin rashes in darker skin types contributed to this initial misdiagnosis. However, we believe it was clear that the patient’s rash and history on initial presentation were not in keeping with urticaria, or an allergic skin rash. However, a further point to consider is that dermatomyositis is rare, and so those working in primary care are less familiar with its manifestations. Medical resources have historically had a tendency to use images of people with lighter skin tones to demonstrate skin diseases. Over the last few years, several textbooks and online resources have become available specifically showing skin conditions in different skin tones, for example, the Mind the Gap handbook. These resources are generally excellent; however, they tend to focus on common skin disorders. In addition, images of dermatomyositis in medical textbooks are predominantly of white skin. If medical education resources were to include examples of dermatomyositis in a variety of skin tones it is possible that diagnostic confidence and proficiency would improve, and racial disparities would be reduced. This is especially important in a multicultural society like the United Kingdom. Key learning points Lack of awareness of skin rashes in diverse skin types contributes to misdiagnosis and worse outcomes for patients with ethnic minority backgrounds, including those with dermatomyositis. Increasing awareness and education surrounding the skin manifestations in diverse skin types is a key priority for medical education, including in rheumatology. New initiatives aimed at improving our understanding of skin manifestations in diverse skin types are underway.

Abstract 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 <0.05) (Table 1). Among these, ERAP2, an enzyme involved in MHC-I ligand processing and a known risk factor for inflammatory diseases, had the largest fold change (-0.64 95%CI -1.20 to -0.07, p = 0.03). Network analysis revealed that the 17 DEPs were significantly enriched (p < 0.001) in the PD+ group. KEGG pathway analysis identified the association of the DEPs in leukocyte transendothelial migration (strength 1.5 FDR=0.04). GO analysis of the DEPs revealed involvement in immunoglobulin receptor binding (strength 2.28 FDR=0.03). 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.