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Background/Purpose Pathogenic antibody-secreting cells (ASC) are poorly characterized in human lupus nephritis (LN). Our objective was to compare the single cell molecular signature of ASC in kidney and urine from patients with active LN, either untreated or after immunosuppressive therapy failure. Methods ASC were identified by anti-CD138 staining on fixed renal biopsies from patients with active LN. We sorted single-ASC from fresh renal biopsies to perform gene expression profiling. ASC transcriptional program from urine of untreated LN patients was assessed at diagnosis and after a prospective follow up during induction therapy. Results Interstitial infiltrates of CD138+ ASC were found in untreated (N=15) and refractory patients (N=6). Single cell molecular signature of kidney ASC from untreated patients revealed that these cells were mostly plasmablasts and contrasted with ASC signature from patients with mycophenolate mofetil failure that expressed long-lived plasma cells genes and clustered with long-lived bone marrow ASC from healthy donors. A plasmablast signature was observed in urine ASC at diagnosis, similar to their kidney counterpart. The concentration of urine ASC from 22 untreated patients correlated with ISN/RPS classification, with higher concentration in class IV patients (p Conclusion These results suggest that plasmablasts infiltrate kidney of untreated LN patients, while kidney long-lived ASC may contribute to the failure of immunosuppressive therapy. Acknowledgement This work was funded by FOREUM.

Background Clinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification. Methods With the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. An inception cohort prospectively followed for 6 and 14 months was studied to validate the results in early cases and analyze if cluster assignment was modified with time. Results Four clusters were identified Three aberrant clusters were ‘acute phase inflammatory’, ‘T cell immunity’, and ‘interferon’, each including all diagnoses, were defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern, to which 74% of healthy controls clustered with patients. The inception cohort showed that most patients were either assigned always to the same cluster or moved from the healthy-like cluster to a single aberrant cluster resembling the relapsing-remitting dynamic of these diseases, showing that single aberrant molecular signatures characterize each individual patient. Conclusions Patients with SADs share molecular signatures and can be therefore stratified into three disease clusters differentiating each patient into a specific molecular disease pathway. Such assignment is stable with time. These results have important implications for understanding disease progression and therapy design marking a paradigm shift in our view of SADs. Acknowledgment This work has been supported through a grant from the Innovative Medicines Initiative Joint Undertaking No. 115565 and in-kind and in-cash contributions from the EFPIA partners. G.B. is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Health Ministry), through the Sara Borrell subprogram (CD18/00153). The authors would like to particularly express their gratitude to the patients, nurses and many others who helped directly or indirectly in the consecution of this study.

Background Rheumatoid Arthritis (RA) is a chronic and heterogenous condition characterized by inflammatory involvement of the synovial membrane in multiple joints. Synovial biopsies are used in research setting in order to identify diagnostic and theranostic markers. Many studies have shown a high degree of heterogeneity in histological and transcriptomic profiles between patients. Objectives We wanted to explore histological and transcriptomic profile of synovial biopsies across pairs of joints in the same patients to assess heterogeneity at the individual level. Methods Synovial biopsies were performed simultaneously in one small and one large joint per patient using needle-arthroscopy for the knee and US-guided needle biopsy for the hand or foot. Synovium from individuals with osteoarthritis (OA) were used as control. Paraffine-embedded samples were stained for CD3, CD 20, CD 68 and CD138. Whole-tissue RNA was extracted and hybridized on GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix). The samples were tested for RNA integrity by Bioanalyzer (Agilent). Normalization and statistical analyzes were performed on Genespring. Pathway analysis were performed using DAVID. Results 10 RA patients were included (females: 10/10, ACPA/RF positivity: 8/10, mean age (± SEM): 54.4 (± 4.4) years, mean disease duration (± SEM): 13.3 (± 3.7) years, mean DAS28CRP (± SEM): 5.01 (± 0,34), mean HAQ (± SEM): 1.7 (± 0.28)). Quantification of histological markers did not show differences in population of macrophages, plasmocytes, T and B Cells, across pairs of joints. After correction for multiple comparisons, no transcripts were differentially expressed between large and small joints. Similarly, we did not find any significant difference in the expression of transcripts involved in pathways (TCR-activation and cell-division) specifically overexpressed in RA compared to OA synovial tissue. In order to increase our ability to observe pair-wise differences in gene expression profiles, we studied correlations between transcripts significantly overexpressed in RA compared to OA joints with a fold change > 2 (n = 581) and clinical or biological markers of disease activity (DAS28-CRP, CRP, Physician Global Assessment of disease activity). Similar patterns of correlations indicated that disease activity was not driven by different pathways in small versus large joints. Conclusion This study is an important methodological milestone in the field of synovial biopsies, as it indicates that cellular and molecular alterations occurring in RA synovitis are similar across small and large joints from the same patient. Hence, biopsy of a single joint is representative and can be used to explore pathogenic processes or potential biomarkers in RA. Acknowledgement This work was funded in part by grants from Cap48 (RTBF), Fonds National de la Recherche Scientifique (FNRS, Communaute francaise de Belgique) and Fondation Saint-Luc. Disclosure of Interests Clement Triaille: None declared, Louise Vansteenkiste: None declared, Laurent Meric de Bellefon: None declared, Adrien Nzeusseu: None declared, Christine Galant: None declared, Patrick Durez Speakers bureau: Bristol-Myers Squibb, Eli Lilly, Sanofi, Celltrion, Bernard Lauwerys: None declared

Background Recurrent fever syndromes have a significant impact on health-related quality of life (HRQoL).1 Canakinumab (CAN) has demonstrated efficacy and safety in patients with colchicine-resistant familial Mediterranean fever (crFMF), hyper-immunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD) and tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in the pivotal, Phase 3, CLUSTER trial (NCT02059291),2 but there are limited published data on the impact of CAN on the HRQoL, work/school and social life of these patients. Objectives To evaluate effect of CAN on HRQoL, work/school and social life of patients in the 3 disease cohorts (crFMF, HIDS/MKD, and TRAPS) in a double blinded randomised study. Methods The detailed study design was reported previously.2 The HRQoL of patients treated with CAN was assessed at Baseline (BL), Week 17 (Wk17) and Week 41 (Wk41) in patients who fully responded (absence of flares), either to 150 mg q4w CAN, or to 300 mg q4w CAN after up dosing. Methods used were the Child Health Questionnaire (CHQ)-PF50 physical (PhS) and psychosocial (PsS) summary scores (children >5– Results Patients showed a high impairment of HRQoL at baseline in all 3 cohorts (crFMF n=31, HIDS/MKD n=37 and TRAPS n=22). At Wk17, a moderate to large treatment effect, either with 150 mg or 300 mg q4w CAN, was observed by an improvement in the CHQ-PF50 PhS and PsS (increased >5), SF-12 PCS (increased >5) and SDS scores (decreased below 2). At Wk41, the number of patients on CAN was limited (crFMF n=9, HIDS/MKD n=6 and TRAPS n=4) due to the design of the trial (randomised withdrawal part). For the patients who remained on CAN, the improvement in HRQoL, work/school and social life was sustained. Conclusion Treatment with CAN led to sustained improvement of HRQoL, work/school and social life in patients with crFMF, HIDS/MKD and TRAPS. References [1] Sahin, et al. Eur Rev Med Pharmacol Sci. 2013;17:958–963. [2] De Benedetti, et al. NEJM 2018;378:1908–1990. Disclosure of Interests Helen J. Lachmann Grant/research support from: SOBI, Novartis, Consultant for: Novartis, Takeda, Speakers bureau: SOBI. Novartis, Bernard Lauwerys: None declared, Paivi Miettunen: None declared, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB, Gerd Horneff: None declared, Riva Brik: None declared, Rafaelle Manna: None declared, Sara Murias: None declared, Sinisa Savic Grant/research support from: Novartis and Sobi, Serge Smeets Employee of: Novartis, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Anna Simon: None declared

Background In patients (pts) with polyarticular-course juvenile idiopathic arthritis (pJIA), SC abatacept (ABA) 125 mg weekly has a similar pharmacokinetic profile, therapeutically equivalent efficacy and comparable safety to IV ABA 10 mg/kg every 4 weeks.1 Although some data on paediatric pt-reported outcomes (PRO) have been published for IV ABA,2 PRO data following treatment with SC ABA have not. Objectives This analysis examined the effect of SC ABA treatment on PROs (activities of daily living [ADL] limitation questionnaire of parent/caregiver, childhood HAQ [CHAQ]-DI, and parent global assessment of overall pt well-being [PaGA]) in 6–17-year pts with active pJIA in a Phase III trial (NCT01844518). Methods Pts with pJIA aged 2–17 years with an inadequate response/intolerance to ≥1 DMARD were enrolled in this single-arm, open-label study and received SC ABA weekly for 4 months based on body weight tier (10– 50 kg [125 mg ABA]). JIA-ACR 30 criteria (ACR Pediatric 30) responders at Month 4 could receive ABA for another 20 months. For the 6–17-year cohort reported here, ADL limitation questionnaire of parent/caregiver (mean [SD] number of days [D] of parental/caregiver missed activity, paid care and missed school [absolute values per month and percentage of D missed per month relative to an assumed average of 20 school D/month]); CHAQ-DI (0–3 scale across 8 domains of disability component); and PaGA (0–100 mm visual analogue scale) were evaluated. Results Baseline characteristics of the 173 pts with pJIA from the 6–17-year cohort were: median (min, max) age, 13.0 (6.0, 17.0) years; median (min, max) number of active joints, 10.0 (2.0, 42.0); 78.6% of pts used MTX (median dose: 11.6 mg/m2/week); and 26.6% were with prior biologic failure. All ADL limitation components improved from baseline to D113 (Month 4); these improvements were largely maintained at D309 (Figure). Relative percentage D missed from school decreased from 15% (D1) to 5.5% (D309, Figure D). CHAQ-DI and PaGA improved from baseline to D309 (Table). Further 2-year data are pending. Conclusions In this analysis of patients with pJIA aged 6–17 years, SC abatacept demonstrated a beneficial effect on PROs including reductions in activity limitation and disability (CHAQ-DI) and improvement in well-being (PaGA) up to D309. References Lovell D, et al. Arthritis Rheumatol 2016;68(suppl 10): Abstract 948. Ruperto N, et al. Arthritis Care Res 2010;62:1542–51. Disclosure of Interest N. Ruperto Grant/research support from: The G. Gaslini Hospital has received contributions from the following industries for the coordination activity of the PRINTO network: Bristol-Myers Squibb, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer,sanofi-aventis, Schwarz Biosciences, Abbott, Francesco Angelini S.P.A., Sobi, Merck Serono, Consultant for: AbbVie, Amgen, Biogen Idec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, sanofi-aventis, Servier, Takeda, UCB Biosciences GmbH, Speakers bureau: AbbVie, Amgen, Biogen Idec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, sanofi-aventis, Servier, Takeda, UCB Biosciences GmbH, H. Brunner: None declared, N. Tzaribachev: None declared, G. Vega-Cornejo: None declared, I. Louw: None declared, J. Anton Grant/research support from: Bristol-Myers Squibb, Novartis, Pfizer, AbbVie, GSK, Sobi, Roche, Alexion, Sanofi, Genzyme, Consultant for: Novartis, Sobi, Roche, Gebro, Pfizer, AbbVie, Alexion, Speakers bureau: Novartis, AbbVie, Pfizer, Sobi, Roche, Gebro, D. Viola: None declared, I. Foeldvari: None declared, V. Keltsev: None declared, D. Kingsbury: None declared, C. Wouters: None declared, B. Lauwerys: None declared, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, R. Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Banerjee Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Martini: None declared, D. Lovell Grant/research support from: National Institutes of Health, NIAMS, Consultant for: AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Janssen, Speakers bureau: Genentech