Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by sustained type I interferon signalling and widespread immune dysregulation. Low-density neutrophils (LDNs) are expanded in SLE and display pro-inflammatory and tissue-damaging properties. However, their metabolic phenotype remains poorly defined. Here, we performed a comprehensive metabolic characterisation of circulating LDNs and normal-density neutrophils (NDNs) from patients with SLE and matched healthy individuals (HC). Neutrophil subsets were isolated from peripheral blood of SLE patients and HC donors using a two-step protocol of negative selection and Percoll density centrifugation. Immunophenotyping phenotype was carried out by flow cytometry to assess phenotypic expression of common neutrophil markers CD15, CD16, CD10, CD66b, CD62L, MPO, and IL-1β. Bioenergetic profiling of LDNs and NDNs was performed in situ using the Seahorse MitoStress test to measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Metabolic flexibility and phenotypic alterations were assessed in LDNs and NDNs following inhibiting mitochondrial metabolism with oligomycin and glycolysis with 2DG. We found that SLE LDNs exhibit an immature phenotype compared with autologous and healthy NDNs, as determined transcriptionally by C/EBPε and by surface protein expression levels of CD10. Both LDNs and NDNs from SLEDAI≥4 patients demonstrated significantly elevated ECAR relative to HC neutrophils. Further, SLE LDNs displayed enhanced metabolic flexibility, with the capacity to switch towards a glycolytic phenotype under metabolic stress conditions. Inhibition of glycolysis altered the inflammatory and maturation-associated phenotype of both SLE neutrophil subsets, indicating a direct link between cellular metabolism and pathogenic neutrophil function. Collectively, these findings identify fundamental metabolic alterations in SLE neutrophil subsets and support neutrophil immunometabolism as a potential therapeutic target in SLE.

Patients with systemic lupus erythematosus (SLE) exhibit significant susceptibility to severe bacterial infections, a leading cause of mortality. A key host defence mechanism is immunothrombosis, wherein activated monocytes rapidly upregulate tissue factor (TF) to initiate localized fibrin deposition that traps and contains pathogens. Effective immunothrombosis is therefore critical for preventing microbial dissemination. This process appears deficient in SLE, a disease defined by a systemic prothrombotic state, yet poor infection outcomes. A recently discovered molecular interaction suggests that TF directly binds to the interferon-α receptor (IFNAR1), acting as a rheostat to suppress interferon signalling. We hypothesize that in SLE, this regulatory axis is disrupted. The dominant, sustained interferon-stimulated gene (ISG) signatures in monocytes limit their capacity for TF upregulation in response to bacterial challenge, thereby impairing immunothrombosis and compromising bacterial containment. Supporting this, SLE patients with secondary antiphospholipid syndrome who have lower interferon signatures display markedly elevated TF levels and a different thrombotic profile, demonstrating the inverse relationship in a clinical subset. Furthermore, TF induction in monocytes is glycolysis-dependent, and SLE monocytes are known to have profound metabolic alterations. The chronic interferon state may thus impose a metabolic constraint that further limits the bioenergetic capacity for a robust TF response. Therefore, the confluence of interferon-driven suppression and metabolic dysfunction in SLE monocytes provides a compelling explanation for the failure of immunothrombosis, directly linking a core disease feature to infection susceptibility.

Systemic lupus erythematosus (SLE) is a lifelong autoimmune condition with multi-system involvement that is associated with morbidity, mortality, and poor quality of life. The key aim of management should be to empower individuals with SLE to manage their condition, suppressing systemic disease activity, and preventing organ damage. This guideline builds on and expands the recommendations developed for the first guideline published in 2017 for adults living with SLE. This comprehensive life-course guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Working Group (GWG) comprising healthcare professionals with expertise in paediatric and adult SLE, and people with lived experience. The GWG reviewed published guidelines, undertook a systematic literature review and utilised expertise from specialist lupus centres across the UK and patient representatives to formulate a list of 102 recommendations with corresponding strength of recommendations and agreement scores. These recommendations encompass advances in the assessment, diagnosis, monitoring, general approaches to management, non-pharmacological and pharmacological management of SLE, organ-specific treatment including lupus nephritis and cutaneous lupus erythematosus, as well as the delivery of care in the context of the UK healthcare system. Furthermore, we have provided research and audit recommendations to support equitable access to care and improve health outcomes in SLE.

BACKGROUND:Systemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses linked to immunometabolic perturbations. While mitochondrial dysfunction has been implicated in SLE, its cell-type-specific impact on immune subsets remains underexplored. METHODS:We repurposed existing RNA-seq data from SLE patient peripheral blood mononuclear cells, with a focus on nuclear-encoded mitochondrial (NEmt) genes, as well as mitochondrial genes themselves, to identify differentially expressed genes compared to healthy controls. Mitochondrial stress tests were performed on freshly isolated CD4+ T cells, CD8+ T cells, B cells, and monocytes from SLE patients and healthy donors to assess bioenergetic function. RESULTS:RNA-seq revealed that both NEmt genes and mitochondrial genes were downregulated in the PBMC population of SLE patients. In situ mitochondrial stress tests revealed significant reductions in oxygen consumption rate (OCR), indicating impaired oxidative phosphorylation (OXPHOS) across all immune subsets, while extracellular acidification rate (ECAR), a marker of glycolysis, remained unchanged. These findings highlight immune-cell-specific mitochondrial bioenergetic failure in SLE, without compensatory glycolytic adaptation. CONCLUSION:Our results position mitochondrial fitness as a novel therapeutic target in SLE. We propose leveraging high-throughput screening of mitochondria-targeted compounds, including FDA-approved agents, to enhance OXPHOS, regulate mitophagy, or mitigate oxidative stress. This precision-based approach offers a paradigm shift from conventional immunosuppression to metabolic recalibration, with the potential to restore immune homeostasis in SLE. Systemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses linked to immunometabolic perturbations. While mitochondrial dysfunction has been implicated in SLE, its cell-type-specific impact on immune subsets remains underexplored.Using existing RNA-seq data we focused on nuclear-encoded mitochondrial (NEmt) genes, as well as mitochondrial genes themselves. Mitochondrial stress tests were performed on freshly isolated CD4+ T cells, CD8+ T cells, B cells, and monocytes from SLE patients and healthy donors to assess bioenergetic function.RNA-seq revealed that both NEmt genes and mitochondrial genes were downregulated in the PBMC population of SLE patients. In situ mitochondrial stress tests revealed significant reductions in oxygen consumption rate, indicating impaired oxidative phosphorylation across all immune subsets, while glycolysis remained unchanged. These findings highlight immune-cell-specific bioenergetic failure in SLE and propose mitochondrial fitness as a novel therapeutic target in SLE. This precision-based approach offers a paradigm shift from conventional immunosuppression to metabolic recalibration.

Introduction The inclusion of National Institutes of Health (NIH) activity (AI) and chronicity (CI) indices in the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis (LN) aims to provide a precise characterization of the amount of active and chronic lesions next to lupus class. We here investigate the distribution of NIH indices within two international LN cohorts, their relationship with the ISN/RPS classes and which lesions most significantly contribute to these scores. Methods We collected 194 biopsies from two cohorts of patients with LN and calculated the NIH AI and CI according to the revised 2018 ISN/RPS classification. For statistical analysis we mainly used non-parametric tests. An exploratory factor analysis was applied to the lesion scores. Results The NIH AI score was usually medium-low, reaching a maximum value of 16/24, while the NIH CI reached 10/12. Both indices were higher in classes III, IV and mixed compared to others (p<.0001). Endocapillary hypercellularity was present in more than 70% biopsies, showing a strong correlation with neutrophils/karyorrhexis (r=0.78, p<.0001) and cellular crescents (p<.0001). Chronic lesions showed a strong correlation with each other (p<.0001), except for fibrous crescents which had the strongest correlation with cellular crescents (r=0.33, p<.0001). The inclusion of all lesions in an exploratory factor analysis uncovered two underlying main factors that accurately reflect the NIH AI and CI. Conclusion This study revealed key aspects of the NIH AI and CI that may guide future modifications of these indices, leading to a more balanced and reliable scoring system.

Introduction:The inclusion of National Institutes of Health (NIH) activity index (AI) and chronicity index (CI) in the ISN/Renal Pathology Society (ISN/RPS) classification of lupus nephritis (LN) aims to provide a precise characterization of the amount of active and chronic lesions next to lupus class. We here investigate the distribution of NIH indices within 2 international LN cohorts, their relationship with the ISN/RPS classes and which lesions most significantly contribute to these scores. Methods:We collected 194 biopsies from 2 cohorts of patients with LN and calculated the NIH AI and CI according to the revised 2018 ISN/RPS classification. For statistical analysis we mainly used nonparametric tests. An exploratory factor analysis was applied to the lesion scores. Results:The NIH AI score was usually medium-low, reaching a maximum value of 16 of 24, whereas the NIH CI reached 10 of 12. Both indices were higher in classes III, IV, and mixed compared with others (P < 0.0001). Endocapillary hypercellularity was present in > 70% of biopsies, showing a strong correlation with neutrophils/karyorrhexis (r = 0.78, P < 0.0001) and cellular crescents (P < 0.0001). Chronic lesions showed a strong correlation with each other (P < 0.0001), except for fibrous crescents which had the strongest correlation with cellular crescents (r = 0.33, P < 0.0001). The inclusion of all lesions in an exploratory factor analysis uncovered 2 underlying main factors that accurately reflect the NIH AI and CI. Conclusion:This study revealed key aspects of the NIH AI and CI that may guide future modifications of these indices, leading to a more balanced and reliable scoring system.

Background/Aims Idiopathic inflammatory myopathy (IIM) is characterised by myositis, which can impact activities of daily living. The 2022 BSR IIM management guideline recommends assessing/managing factors associated with poor mental wellbeing and quality of life. Research into anxiety and depression associated with IIM is limited. This study aims to investigate associations between anxiety/depression and IIM disease activity. Methods The MYOPROSP study recruited UK adults with verified IIM throughout a 36 month period between 2016 and 2020. Patient questionnaires were collected at three, six, and 12 months. Participants completed the EQ-5D-5L questionnaire, which includes a question relating to anxiety and depression with five possible responses: "I am (not/slightly/moderately/severely/extremely) anxious or depressed". The cohort was divided by response to the EQ-5D-5L anxiety/depression question at the time of recruitment. Disease activity was assessed using International Myositis Assessment & Clinical Studies Group (IMACS) Disease Activity Core Set Measures (see Table 1) and summarised across each EQ-5D-5L anxiety/depression group. The EQ-5D-5L visual analogue scale (VAS) relating to "overall health" (higher values correspond to better health) this value was summarised across each EQ-5D-5L anxiety/depression group. Only participants with complete data at recruitment were included in analysis. One-way ANOVA was performed to determine statistical significance (p < 0.05) of each IMACS Disease Activity Core Set Measure and EQ-5D-5L VAS across anxiety/depression groups. Results Complete data on 35 participants (71% female) was collected. All participants reported to have no, slight, or moderate anxiety/depression (i.e. no participant reported severe or extreme anxiety/depression) (Table 1). The "not anxious/depressed" group demonstrated higher EQ-5D VAS values (reflecting better perceived health), shorter disease duration, and higher CK levels, compared to groups with "slight" and "moderate" anxiety/depression. All other investigated variables did not consistently vary across anxiety/depression groups. One-way ANOVA identified that only disease duration and EQ-5D VAS were significantly associated with EQ-5D-5L anxiety/depression group. Conclusion Anxiety and depression are associated with longer disease duration and poorer overall health in adults with IIM. These findings suggest that anxiety/depression in adults with IIM may be due to sustained muscle damage and resulting impacts upon activities of daily living and quality of life, rather than disease activity.

A bimodal pattern of mortality in systemic lupus erythematosus (SLE) exists. Early-stage deaths are predominantly caused by infection, whereas later-stage deaths are mainly caused by atherosclerotic disease. Further, although SLE-related mortality has reduced considerably in recent years, cardiovascular (CV) events remain one of the leading causes of death in people with SLE. Accelerated atherosclerosis in SLE is attributed to both an increase in traditional CV risk factors and the inflammatory effects of SLE itself. Many of these changes occur within the microenvironment of the vascular-immune interface, the site of atherosclerotic plaque development. Here, an intimate interaction between endothelial cells, vascular smooth muscle cells, and immune cells dictates physiological vs pathological responses to a chronic type 1 interferon environment. Low-density neutrophils (LDNs) have also been implicated in eliciting vasculature-damaging effects at such lesion sites. These changes are thought to be governed by dysfunctional metabolism of immune cells in this niche due at least in part to the chronic induction of type 1 interferons. Understanding these novel pathophysiological mechanisms and metabolic pathways may unveil potential innovative pharmacological targets and therapeutic opportunities for atherosclerosis, as well as shed light on the development of premature atherosclerosis in patients with SLE who develop CV events.

Systemic lupus erythematosus (SLE) is an autoimmune disease, the pathophysiology and genetic basis of which are incompletely understood. Using a forward genetic screen in multiplex families with SLE, we identified an association between SLE and compound heterozygous deleterious variants in the non-receptor tyrosine kinases (NRTKs) ACK1 and BRK . Experimental blockade of ACK1 or BRK increased circulating autoantibodies in vivo in mice and exacerbated glomerular IgG deposits in an SLE mouse model. Mechanistically, NRTKs regulate activation, migration, and proliferation of immune cells. We found that the patients’ ACK1 and BRK variants impair efferocytosis, the MERTK-mediated anti-inflammatory response to apoptotic cells, in human induced pluripotent stem cell (hiPSC)-derived macrophages, which may contribute to SLE pathogenesis. Overall, our data suggest that ACK1 and BRK deficiencies are associated with human SLE and impair efferocytosis in macrophages.

The objective of this guideline is to provide up-to-date, evidence-based recommendations for the management of SLE that builds upon the existing treatment guideline for adults living with SLE published in 2017. This will incorporate advances in the assessment, diagnosis, monitoring, non-pharmacological and pharmacological management of SLE. General approaches to management as well as organ-specific treatment, including lupus nephritis and cutaneous lupus, will be covered. This will be the first guideline in SLE using a whole life course approach from childhood through adolescence and adulthood. The guideline will be developed with people with SLE as an important target audience in addition to healthcare professionals. It will include guidance related to emerging approved therapies and account for National Institute for Health and Care Excellence Technology Appraisals, National Health Service England clinical commissioning policies and national guidance relevant to SLE. The guideline will be developed using the methods and rigorous processes outlined in ‘Creating Clinical Guidelines: Our Protocol’ by the British Society for Rheumatology.

Neonatal antiphospholipid syndrome (APS) is a rare condition that can occur due to either transplacental transfer of antiphospholipid antibodies (aPL) from the mother, or, more rarely, de novo in the infant. The condition manifests as arterial, venous or mixed thromboses. Arterial thromboses seem to be much more common than venous, with strokes being the most prevalent. Very few venous thromboses have been reported, and of these, only one involved the inferior vena cava. In that case, the mother was diagnosed with lupus 2 years prior to pregnancy; the thrombus was primarily in the left renal vein, although it extended into the inferior vena cava; only anticardiolipin antibodies were positive; and these disappeared in the infant by 4 months of age, but persisted in the mother. To the best of our knowledge, we report the first case of inferior vena cava thrombosis in a neonate with transiently positive anticardiolipin and anti-beta 2 glycoprotein antibodies, born to a mother found to be triple positive for aPLs.

ObjectiveTo develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR.MethodsThis international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators’ consensus as the gold standard.ResultsThe 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1–7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti–β2-glycoprotein I antibodies). Patients accumulating at least three points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria vs the 2006 revised Sapporo classification criteria had a specificity of 99% vs 86%, and a sensitivity of 84% vs 99%.ConclusionThese new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.

Introduction:Lupus nephritis (LN) class III or IV is strongly related to patient mortality and morbidity. The interobserver agreement of endocapillary hypercellularity by routine light microscopy, one of the most important lesions determining whether class III or IV is present, is moderate. In IgA nephropathy (IgAN), the presence of glomerular CD68+ cells was found to be a good surrogate marker for endocapillary hypercellularity. We investigated whether the presence of glomerular CD68+ cells could serve as a surrogate marker for endocapillary hypercellularity as well in LN.Methods:A total of 92 LN biopsies were scored for the number of glomerular CD68+ cells using CD68 staining, including endocapillary hypercellularity and the activity index (AI). A new AI was calculated in which CD68+ cells replaced endocapillary hypercellularity. Clinical parameters were obtained from time of biopsy, 1 year after, and 2 years after.Results:The number of glomerular CD68+ cells significantly correlated with endocapillary hypercellularity. A cutoff value of 7 for the maximum number of CD68+ cells within 1 glomerulus in a biopsy yielded a sensitivity of 88% and a specificity of 67% for the presence of endocapillary hypercellularity. Both endocapillary hypercellularity and CD68+ cells correlated with renal function during follow-up. The current and the new AI correlated equally well with the clinical outcome.Conclusion:In LN, CD68+ cells can be used as a surrogate marker for endocapillary hypercellularity.

Abstract Background/Aims Giant cell arteritis (GCA) is a chronic, idiopathic, granulomatous vasculitis of medium and large arteries comprising overlapping phenotypes of cranial arteritis and extracranial GCA. Vascular complications are generally due to delay in diagnosis and initiation of effective treatment. Due to the imminent risk of visual loss and other ischaemic complications it is vital to secure the diagnosis and it is equally important to exclude the mimics as the treatment of GCA has it's own complications. The objective of this quality improvement project was to assess the performance of Southend GCA Pre-test Probability Score (GCA PS) in a cohort of patients who were referred urgently with suspected GCA to the Rheumatology Department of Addenbrooke’s Hospital. Methods We analysed the data of 50 new patients seen between Aug 2019 and Feb 2020. GCA PS were calculated based on the information from GPs (clinical and biochemical data). The likely hood of GCA was determined on review after 1 month, based on the clinical, biochemical, histopathological data and response to steroids. Results A total of 50 cases were included in the study. Thirty-eight (76%) of them were females while 12(24%) were males. The median age was 68.5. The median probability score was 12, it ranged between 0 to 24. Finally, 25 patients were diagnosed as likely to have GCA based on clinical, biochemical, histopathological findings and response to steroids. The lowest probability score among those who had a positive biopsy was 10. The p value for the likelihood of GCA when the probability score was 10 or higher was 0.0001 which was very significant. Conclusion GCA pre-test probability score is a very promising and utilitarian tool for risk stratification of patients with suspected GCA and prediction of the likelihood of GCA. It enables exclusion of GCA in cases with low probability score and to have a higher degree of scrutiny in those with intermediate and high probability scores. Clinical diagnostic algorithm based on the BSR guidelines could further be utilised for confirmation. Disclosure P. Kadamban: None. S. Pattapola: None. H. Alkoky: None. N. Jordan: None. B. Gupta: None.

OBJECTIVES:To assess non-invasive imaging for detection and quantification of gland structure, inflammation and function in patients with primary Sjogren's syndrome (pSS) using PET-CT with 11C-Methionine (11C-MET; radiolabelled amino acid), and 18F-fluorodeoxyglucose (18F-FDG; glucose uptake marker), to assess protein synthesis and inflammation, respectively; multiparametric MRI evaluated salivary gland structural and physiological changes. METHODS:In this imaging/clinical/histology comparative study (GSK study 203818; NCT02899377) patients with pSS and age- and sex-matched healthy volunteers underwent MRI of the salivary glands and 11C-MET PET-CT. Patients also underwent 18F-FDG PET-CT and labial salivary gland biopsies. Clinical and biomarker assessments were performed. Primary endpoints were semi-quantitative parameters of 11C-MET and 18F-FDG uptake in submandibular and parotid salivary glands and quantitative MRI measures of structure and inflammation. Clinical and minor salivary gland histological parameter correlations were explored. RESULTS:Twelve patients with pSS and 13 healthy volunteers were included. Lower 11C-MET uptake in parotid, submandibular and lacrimal glands, lower submandibular gland volume, higher MRI fat fraction, and lower pure diffusion in parotid and submandibular glands were observed in patients vs healthy volunteer, consistent with reduced synthetic function. Disease duration correlated positively with fat fraction and negatively with 11C-MET and 18F-FDG uptake, consistent with impaired function, inflammation and fatty replacement over time. Lacrimal gland 11C-MET uptake positively correlated with tear flow in patients, and parotid gland 18F-FDG uptake positively correlated with salivary gland CD20+ B-cell infiltration. CONCLUSION:Molecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS.

Objectives Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE. Methods Proteomic/phosphoproteomic analyses were performed in healthy control (HC) normal density neutrophils (NDNs), SLE NDNs and autologous SLE LDGs. The biophysical properties of these neutrophil subsets were analysed by real-time deformability cytometry and lattice light-sheet microscopy. A two-dimensional endothelial flow system and a three-dimensional microfluidic microvasculature mimetic (MMM) were used to decouple the contributions of cell surface mediators and biophysical properties to neutrophil trafficking, respectively. Results Proteomic and phosphoproteomic differences were detected between HC and SLE neutrophils and between SLE NDNs and LDGs. Increased abundance of type 1 interferon-regulated proteins and differential phosphorylation of proteins associated with cytoskeletal organisation were identified in SLE LDGs relative to SLE NDNs. The cell surface of SLE LDGs was rougher than in SLE and HC NDNs, suggesting membrane perturbances. While SLE LDGs did not display increased binding to endothelial cells in the two-dimensional assay, they were increasingly retained/trapped in the narrow channels of the lung MMM. Conclusions Modulation of the neutrophil proteome and distinct changes in biophysical properties are observed alongside differences in neutrophil trafficking. SLE LDGs may be increasingly retained in microvasculature networks, which has important pathogenic implications in the context of lupus organ damage and small vessel vasculopathy.

Background: Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease. African ancestry is associated with an increased risk of Lupus Nephritis (LN). Anti-DNA autoantibodies play a major role in the development of LN and anti-Ro antibodies have also been implicated. McCarty et al suggested that women of African ancestry with the unusual autoantibody combination of anti-Sm, Ro & RNP antibodies (AB) were at increased risk of developing LN (1). Objectives: Our aim was to determine the correlation between autoantibody profile: Sm, Ro and RNP as a combination in the development of LN in patients with African ancestry. We investigated time to the development of LN from SLE onset. Methods: A retrospective case-control study was conducted at Guys and St Thomas NHS Trust, London, United Kingdom. 75 patients with confirmed LN meeting the ACR classification criteria for SLE and Nephritis, were included: African (n=35), Caucasian (n=22) and Asian (n=17) ancestry. LN patients with the combination of Sm, Ro and RNP antibodies (Group 1) were compared to LN patients without this autoantibody combination (Group 2). Demographic data, pathology results and laboratory findings were collected. Anonymised data was analyzed using Statistical Package for Social Sciences (SPSS). Left censorship bias was reduced by use of a database of confirmed LN in our cohort of patients. Research and Development Office approval was obtained for this study. Results: There were 66 (88%) females and 9 (12%) males. The median age in Group 1 was 39 years (range 18-60), while in group 2 the median age was 45 years (range 24-64). We stratified our population based on their antibody status: Of the 75 (100%) patients, 32 (42.6%) patients had the combination of Sm, Ro & RNP antibodies (Group 1) while the remaining 43 (57.4%) patients did not (Group 2). In Group 1, regardless of ethnicity, 29 (90.6%) patients developed LN within 5 years or less from the onset of SLE symptoms, while the remaining 3 (9.4%) developed LN after 5 years. In contrast, in Group 2, 24 (55.8%) patients developed LN within 5 years or less while 19 (44.2%) developed LN after 5 years. (P value = 0.002) Further stratification was based on ethnicity and antibody (AB) status to investigate the time to develop LN from SLE symptom onset: African ancestry with positive AB, African with negative AB, Asian with positive AB, Caucasian with positive AB and Asian & Caucasian with negative Ab. Analysis showed that of 29 (38.7%) African ethnicity patients with the autoantibody combination, 19 (65.5%), developed LN within 5 years. In comparison, 46 (61.3%) patients, independent of ethnicity and AB status, developed LN after 5 years (P value = 0.01). Conclusion: Patients with the unusual autoantibody combination of Sm, Ro & RNP developed LN significantly earlier than patients who did not have this combination. This autoantibody combination was significantly over represented in the African ancestry patients. Our data suggests that African ancestry patients with this autoantibody combination are at increased risk of developing LN soon after SLE symptom onset and merit close monitoring for the development of renal disease. References: [1]McCarty GA, Harley JB, Reichlin M. A distinctive autoantibody profile in Black female patients with lupus nephritis. Arthritis & Rheumatism. 1993; 36:1560-1565 Table 1.1 Ethnicity with Autoantibody status showing the rate of progression into Lupus Nephritis. Duration of LN onset Total Less than 5 years after SLE onset More than 5 years after SLE onset Ethnicity with AB status African with positive 19 3 22 African with negative 9 4 13 Asian with positive 5 0 5 Caucasian with positive 5 0 5 Other negatives 15 15 30 Total 53 22 75 Graph 1. Ethnicity with Autoantibody status showing the rate of progression into Lupus Nephritis (P value= 0.01) Disclosure of Interests: Majed Albirdisi: None declared, David d’cruz Grant/research support from: GlaxoSmithKline, Shirish Sangle: None declared, Natasha Jordan: None declared

Background: Saliva and tear flow rates and minor salivary gland biopsy are typically used to assess gland function and disease activity in primary Sjögren’s syndrome (pSS); however, these have limitations. Imaging methods can directly visualize and generate quantitative values in individual glands. 18F-FDG-PET/CT (18F-FDG) measures glucose metabolism, a potential surrogate for inflammation; 11C-methionine-PET/CT (11C-met) is an amino acid PET tracer that assesses protein synthesis, a potential surrogate for gland synthetic function. Objectives: Explore the potential of molecular imaging and multi-parametric MRI to characterize and quantify pSS disease manifestations. Methods: In this pilot imaging study (203818), patients with pSS diagnosed per AECG criteria, with a EULAR Sjögren’s syndrome disease activity index score ≥5, and basal salivary flow >0.0 mL/min or stimulated salivary flow rate ≥0.05 mL/min, underwent 18F-FDG and 11C–met and dynamic contrast-enhanced and diffusion-weighted MRI, followed by minor salivary gland biopsy for histological analysis. Age- and sex-matched healthy volunteers (HV) underwent MRI and 11C-met. HV-pSS mean differences (m-diff; 95% confidence intervals [CI]) were calculated and Pearson’s correlation coefficients (r) estimated. Peak PET standard uptake values (SUVpeak) were used in the correlations and SUVmax values were recorded. All methods were compared with routine clinical and laboratory tests. Results: 12 patients had MRI, 18F-FDG and 11C–met; while HV (n=12) had MRI (n=12) and 11C–met (n=8). A lower 11C-met SUVpeak was seen in the parotid (m-diff: 1.4 g/mL [0.4, 2.3]) and submandibular (m-diff: 2.0 g/mL [0.9, 3.2]) glands in pSS versus HV, as was a trend for lower lacrimal gland uptake (m-diff: 0.5 g/mL [-0.2, 1.3]) in patients with pSS. On structural MRI, the fat fraction (mean%) was higher in pSS vs HV in the submandibular glands (m-diff: -14.8 [CI: -29.3, -0.4]), with similar trends observed in the parotid glands (-11.2 [-24.3, 1.9]). There was a negative correlation between 11C-met uptake and fat fraction (r: -0.7 [-0.9, -0.4]) in the combined parotid glands. There was positive correlation between 11C-met uptake and stimulated salivary flow (r: 0.5 [0.03, 0.8]) and negative correlation for stimulated salivary flow and fat fraction (r: -0.5 (-0.8, -0.1)] in the parotid glands; similar correlations were also seen in the submandibular glands. There was negative correlation between the global lymphoid aggregation score on minor salivary gland biopsy and the combined salivary gland fat fraction (r: -0.7 [-0.9, -0.2]). Parotid gland SUVmax 18F-FDG uptake was higher than historical control values (mean: 1.9 g/ml, [SD: 0.5]1) in some patients (pSS mean SUVmax: 2.8 g/mL [SD: 0.8, range 1.7–4.6]), with positive correlation between 18F–FDG and 11C-met uptake (r: 0.7 [0.2, 0.9]) in the combined salivary glands. Conclusion: Imaging showed clear differences between pSS and HV and correlated with clinical endpoints. Low 11C-met uptake and high fat fraction on MRI may indicate poor residual gland function, while high 18F-FDG and stable 11C-met uptake may define a subpopulation that responds well to anti-inflammatory therapies. References [1] Basu S, et al. Nucl Med Commun 2008; 29:367–73. Acknowledgement: Study/editorial support by Fishawack Indicia Ltd, UK funded by GSK. Disclosure of Interests: Michele Bombardieri Grant/research support from: Celgene, Consultant for: Medimmune, Coziana Ciurtin: None declared, Michalis Kostapanos Consultant for: Is an NHS consultant seconded to the GSK Clinical Cambridge Unit (50%) and has nothing to disclose., Elisa Astorri: None declared, Anwar Tappuni: None declared, Natasha Jordan: None declared, Saleem Azeem Shareholder of: GSK, Teresa Fuller Shareholder of: GSK, Employee of: GSK, Kathleen Port Shareholder of: GSK, Employee of: GSK, Nirav Ratia Shareholder of: GSK, Employee of: GSK, Andre van Maurik Shareholder of: GSK, Employee of: GSK, Calum Gray: None declared, Lucy Kershaw: None declared, Rob Janiczek Shareholder of: GSK, Employee of: GSK, Graham Searle: None declared, Paul Galette Shareholder of: GSK, Employee of: GSK, Marius de Groot Shareholder of: GSK, Employee of: GSK, Neel Patel Shareholder of: GSK, Employee of: GSK, Nicolas Wisniacki Shareholder of: GSK, Employee of: GSK, Mats Bergstrom Shareholder of: GSK, Consultant for: acted as external consultant to GSK, Employee of: GSK, Pilar Jimenez-Royo Shareholder of: GSK, Employee of: GSK, Ruth Tarzi Shareholder of: GSK, Employee of: GSK

Background: Giant cell arteritis (GCA) is a large vessel vasculitis typically affecting patients above the age of 50 years. It is the most common cause of vasculitis affecting adults with a UK prevalence of approximately 0.25% of the population above the age of 55 years [1]. Whilst its clinical presentation can often be non-specific, if left undiagnosed it can lead to devastating visual impairment. However, this has to be balanced with the potential for corticosteroid related adverse effects. The threshold for suspected diagnosis and referral to rheumatology centres from the community and acute medical services is therefore low, leading to a relatively high number of referrals with a wide range of clinical features and potential differential diagnoses. Objectives: To assess the referral characteristics, demographics, management, corticosteroid adverse effects and differential diagnosis of 100 consecutive patients referred with suspected GCA to a tertiary rheumatology centre. Methods: The notes of 100 consecutive patients referred to the rheumatology department at Addenbrookes hospital between August 2016 and January 2018 with suspected GCA were reviewed. Information on patient demographics, comorbidities, presenting symptoms, availability of up to date inflammatory markers, dates of treatment and clinic review, temporal artery biopsy (TAB) date and result, diagnosis and corticosteroid adverse effects were retrieved. Results: Seventy three female and twenty seven male patients (average age 72.3 years) were referred within the time period. General practice referred 69% of the cases and common comorbidities included hypertension and type II diabetes. The most common symptoms were headache (97%), scalp tenderness (79%), jaw claudication (35%) and polymyalgia symptoms (34%). Up to date inflammatory markers were available for 91% of referrals and 92% were commenced on corticosteroids before or at the time of referral with an average starting dose of 43.9mg oral prednisolone. A TAB was performed on 85% of patients, with an average time of 9 days between referral and TAB and 40 days between referral and clinic appointment. TAB was positive for GCA in 13/85 patients. Temporal artery ultrasound (TAU) was not available at our centre. The American College of Rheumatology (ACR) classification criteria for GCA were met by 85% of the patients, but only 69% were given a diagnosis of GCA. Other diagnoses included trigeminal neuralgia, temporo-mandibular dysfunction, toothache and a poorly fitted CPAP mask. Corticosteroid adverse effects were experienced by 45% of patients including weight gain, poorly controlled diabetes, mood and sleep disturbance, and 4% suffered severe complications requiring hospital admission (pneumonia, disseminated nocardia infection and two episodes of upper gastrointestinal bleed). Conclusion: Suspected GCA is a common referral to rheumatology but the non-specific symptoms, quality of referral and potential for visual loss can lead to over-diagnosis. We have found the majority of our referrals to have been appropriate and complete with 85% meeting ACR criteria for GCA and 92% having up to date inflammatory markers. Despite this, 31% of patients received an alternative diagnosis. Increasing the availability of TAU may improve the time to diagnosis and therefore potentially reduce unnecessary exposure to corticosteroids. Our experience highlights the fact that despite a good standard of referral, GCA remains a difficult condition to diagnose and poses an on-going challenge to the rheumatologist. References [1] Yates, M., et al., The prevalence of giant cell arteritis and polymyalgia rheumatica in a UK primary care population. BMC Musculoskelet Disord, 2016. 17: p. 285. Disclosure of Interests: Jobie Evans Grant/research support from: I am currently working on a MD research project looking at the use of magnetic resonance enterography imaging as a screening tool for axial spondyloarthritis in patients with Crohn’s disease. This study is commercially funded by Merck, Sharp and Dohme corporation (MSD)., Natasha Jordan: None declared