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Background Type I interferons (IFN), particularly IFN-αs, are considered to have a pivotal role in SLE. Recently, increased levels of type III IFNs (IFN-λs) have been described to be also associated with SLE. Objectives We measured circulating levels of IFN-λ, IL-17, IL-23, IP-10 and also IFN-α, in a cohort of SLE patients and investigated their association with clinical and laboratory manifestations of the disease. Population controls were investigated as comparators. Methods 261 SLE patients and 276 population controls, identified through the population registry and matched for age, sex, and region of living, were included. All participants were examined by clinician rheumatologist and assessed for current organ manifestations and disease related organ damage. Sera were collected at inclusion and stored at -70* C until analysis. Serum levels of IFN-α, IFN- λ, IL-17, IL-23 and IP-10 were measured in sera by commercial ELISA. Results IFN-λ was detected in 76 (29,1%) patients and IFN-α in 115 (44%). In 108 patients (41.4%) neither of the cytokines was detected. Both IFN-λ and IFN-α were detected more often and in higher levels in patients. IFN-λ levels did not correlate to the levels of IFN-α, and only in 38 (14.5%) patients had detectable levels of both. Levels of IL-17, IL-23 and IP-10 correlated with each other and with IFN-λ. In comparison, only a weak correlation between levels of IFN-α and IL-23 was observed. Detectable levels of IFN-λ were associated with lower incidence of fever, photosensitivity and also arthritis. Patients with detectable IFN-α had active mucocutaneous disease, serositis and lower levels of C3 and C4, and also presence of anti-Ro/SSA and anti-La/SSB. Incidence of nefritis and DVT was lower in this group. Co-detection of IFN-α and IFN-λ was significantly associated with lymphadenopathy, serositis, cortical dysfunction and presence of antiphospolipid antibodies. IFN-α was associated with overall lower disease damage. However, IFN-λ was associated with lower incidence of musculoskeletal, but higher frequency of cerebrovascular damage. The triple detection of IFN-λ, IL-17 and IL-23 was significantly associated with overall higher disease damage score, and particularly higher incidence of renal damage. Conclusions Our study demonstrates that in SLE patients the levels of IFN-α and IFN-λ do not correlate, but rather dissect patient9s groups with different target organs. Triple positivity for IFN-λ, IL-17 and IL-23 is associated with the higher disease damage, in particular kidney damage. References Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity. Wu Q, Yang Q, Lourenco E, Sun H, Zhang Y. Arthritis Res Ther. 2011 Jun 16. Disclosure of Interest None declared

Background There is presently no consensus on how to best measure disease activity in systemic lupus erythematosus (SLE). Available validated measures, such as SLE Disease Activity Index (SLEDAI) and SLE Activity Measure (SLAM), are composite scores that in addition to laboratory tests require investigation by a physician. These scores are insensitive to change and have failed to differentiate treatment responses in clinical trials. It would be an important step forward, for clinical practice and for clinical trials, if one or several biomarkers could be used as proxies for disease activity in SLE. Objectives Our objective is to evaluate cytokines, in combination with basic laboratory tests, as potential disease activity biomarkers. Methods In a cross-sectional setting we examined 433 patients with SLE (fulfilling four or more of the 1982 revised ACR criteria) and 322 age and gender matched population controls. Disease activity was assessed according to both SLEDAI and SLAM by a rheumatologist. Basic laboratory tests and analyses on MSD 30-plex cytokine assay (Mesoscale Discovery, K15054D) were performed on fasting blood samples (total >50 potential biomarkers). The discriminatory power for investigated biomarkers was tested between patients and controls. Spearman correlations with SLAM/SLEDAI scores were calculated among patients. Results Many potential biomarkers discriminated between patients and controls. Best discriminatory power was observed for TNF-α (p=7x10 –63 ), IL-6 (p=2.5x10 –40 ), orosomucoid (p=7.1x10 –38 ), plasma (P)-albumin (p=1.6x10 –36 ) and sedimentation rate (SR) (p=5.6x10 –34 ). The strongest correlations with SLEDAI/SLAM were observed for TNF-α (Spearman ρ=0.32, p=6.0x10 –12 for SLEDAI and Spearman ρ=0.34, p=5.0x10 –13 for SLAM), and for P-albumin (Spearman ρ=-0.33, p=9.0x10 –13 for SLEDAI and Spearman ρ=-0.31, p=5.0x10 –11 for SLAM). As SR is part of SLAM, expected positive correlations were observed (Spearman ρ=0.27, p=7.7x10 -9 for SLEDAI and Spearman ρ=0.48, p=4.0x10 –25 for SLAM). Conclusions Of more than 50 investigated biomarkers TNF-α was the best discriminator between SLE patients and controls. Furthermore TNF-α was the biomarker, which correlated best with disease activity. These correlations were further improved by the ratio between TNF-α and P-albumin. We propose that the TNF-α/P-albumin ratio merits further investigations as a clinically useful biomarker for diagnostic and surveillance purposes in SLE. Disclosure of Interest None declared

Background Microparticles (MPs) are circulating cellular blebs released by activated and apoptotic cells. MPs have been associated with autoimmune diseases (1) and with vascular events in the general population (2). Objectives We investigated the number and phenotype of MPs in patients with systemic lupus erythematosus (SLE) and population based controls. We hypothesised that the MP profile could identify SLE subgroups with previous vascular events and/or antiphospholipid syndrome (APS). Methods 290 consecutive SLE patients and 290 controls, individually matched to the patients were included. Previous vascular events, clinical characteristics and presence of antiphospholipid antibodies (aPL) were tabulated. MPs positive for phosphatidylserine (PS) were identified with lactadherin and measured by flow cytometry. They were phenotyped according to cellular origin (platelet, endothelial or leukocyte) and protein expression (CD40 ligand=CD40L, tissue factor=TF, vascular cell adhesion molecule 1=VCAM-1 or high-mobility group protein B1=HMGB1). C4d expression was measured on endothelial and platelet MPs, regardless of PS expression. Results There was a highly significant difference between SLE patients and controls for all MPs, regardless of origin, p Conclusions Patients with SLE had 2-10 times elevated levels of MPs of various cellular origins in blood. Associations with borderline p-values between MPs of endothelial origin and previous vascular events were found but the subgroup with APS could not be identified by MP profile. Though, analytical challenges remain; the remarkably high levels of MPs in SLE patients may provide new insights into the pathogenesis of SLE, and MPs merit further evaluation as candidate diagnostic biomarkers for SLE. References Pisetsky DS, Ullal AJ, Gauley J, Ning TC. Microparticles as mediators and biomarkers of rheumatic disease. Rheumatology (Oxford). 2012;51(10):1737-46. Lacroix R, Dubois C, Leroyer AS, Sabatier F, Dignat-George F. Revisited role of microparticles in arterial and venous thrombosis. J Thromb Haemost. 2013;11 Suppl 1:24-35. Acknowledgements The work in this abstract will be part of Dr Vikerfors thesis, defended 24 Feb and distributed both electronically and in paper format 30 Jan. Disclosure of Interest None declared

Background Several instruments are used to assess disease activity in systemic lupus erythematosus (SLE). The majority of these depend on a physician9s examination. Systemic Lupus Activity Questionnaire (SLAQ) [1] is a questionnaire, which is based on patients9 assessments of lupus activity. SLAQ was originally developed from the instrument Systemic Lupus Activity Measure (SLAM) [2], which is filled out by physicians. SLAQ has demonstrated good reliability, construct validity and responsiveness in English speaking cohorts [1], but is not validated in Scandinavian languages. Objectives The aim of this study was to compare patients9 (SLAQ) to physicians9 (SLAM) assessments of disease activity in SLE. Additionally we explored how self-assessed disease activity varied with disease duration Methods Consecutive patients with SLE filled out the SLAQ questionnaire before meeting the physician, who evaluated disease activity according to SLAM. SLAQ scorings explored were; 1) SLAQ score (score 0-47), 24 symptom items analogues to SLAM, 2) Symptom Score (score 0-24) positive symptom responses, 3) Flare (score 0-3), presence and severity of lupus flares. 4) Patient numeric rating scale (PNRS, score 0-10), global disease activity. Additionally corresponding items on SLAQ and SLAM were explored. Spearman9s rho was used to calculate correlations and Mann-Whitney U for comparisons. Results 203 patients (79.3% women) were included, median age 45 (IQR 33-57), disease duration 5 years (IQR 0-14). Physician (SLAM-nolab) - patient correlations were good to moderate; SLAQ score (0.685), Symptom Score (0.651), Flares (0.547), PNRS (0.600). Six symptom items had good to moderate correlation between patients and physicians; fatigue (0.640), seizures (0.635), headache (0.604), Raynaud9s (0.560), alopecia (0.508) and joint (0.512). The only symptom item with no correlation was neurological/stroke syndrome (0.109 p=251). Patients with short disease duration less than a year (n=52, 25.6%), had a more active disease by both SLAM (median, IQR) (9, 5-13 vs 6, 3-9 p Conclusions This study indicates that patient assessment by SLAQ can be used to assess disease activity in SLE. However patients with short disease duration had lower correlations indicating greater discrepancy between patients and physicians9 assessments. Notably for the neurological/stroke syndrome there were no correlations between patients and physicians. Nevertheless SLAQ can be used in nursing clinics and in discussions between patients and health care providers. Further studies could evaluate if discussions or alterations of the questions can improve the agreement between SLAQ and health care providers interpretation of signs and symptoms in SLE. References Karlson, E.W., et al., Lupus, 2003. Liang, M.H., et al., Arthritis Rheum, 1988. Disclosure of Interest None declared

Background There are several problems with the current methods for detection of antiphospholipid antibodies (aPL) and there is an on-going discussion about the interpretation of different aPL-tests in everyday practice. (1) Objectives I. To evaluate agreement and performance of two tests for aPL, including a new automated assay. II. To study the importance of isotypes and titers with respect to thrombotic events in patients with Systemic Lupus Erythematosus (SLE). Methods We investigated 712 SLE-patients and 280 controls. Antibodies against cardiolipin and b 2 glycoprotein-I were analysed by a routine ELISA method (Orgentec, Mainz, Germany) and a new, automated method (Elia Cardiolipin IgG/IgM, Elia –β 2 –Glycoprotein I IgG/IgM performed on Phadia 250, Phadia AB, now Thermo Fisher Scientific, Germany). We used three cut-offs for positivity and calculated specificity, sensitivity and odds ratio (OR) for objectively verified previous thrombotic events. Results were compared with outcomes for Lupus anticoagulant (LAC) performed in 380 of the patients. Results Agreement between and performance of both aPL-methods were modest with no strong advantage in performance for either test. Using a cut-off corresponding to established criteria (2) sensitivity for the individual aPL-tests for any previous thrombosis ranged from 3.7 to 24.8% while specificity ranged from 84.7% to 97.7%. Regardless of assay, antibodies of IgG-isotype were associated with venous thrombosis and ischemic cerebrovascular disease while IgM-antibodies were associated with ischemic heart disease. Associations were highly affected by the positivity cut-off-level. ORs for LAC were generally higher than for the specific aPL-tests. For any previous thrombosis, OR (95% Confidence Interval) for LAC was 5.4 (3.1-9.4) while OR for the individual aPL-tests using a cut-off corresponding to established criteria ranged from non-significant to 1.9 (1.03-3.4) with the highest OR for routine ELISA cardiolipin IgG. Conclusions The most interesting finding in this study is that aPL of IgG and IgM isotypes were associated with different types of thrombotic events. Only moderate agreement between, but no clear advantage in relation to thrombotic manifestations, was observed when comparing a routine ELISA for aPL with a new automated method. The LAC test performed better than both aPL-assays. References Galli M. Clinical utility of laboratory tests used to identify antiphospholipid antibodies and to diagnose the antiphospholipid syndrome. Semin Thromb Hemost. 2008 Jun;34(4):329-34. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306. Disclosure of Interest None Declared

Systems biology of SLE : biochemical characterisation of subgroups within sle for improved diagnosis and treatment