BackgroundThis 4 phase project1 jointly supported by EULAR and ACR has led to draft criteria.2 ObjectivesTo simplify and validate the new criteria in a large international cohort.Methods23 expert centres each contributed up to 100 patients with SLE and with non-SLE diagnoses. Diagnoses were verified by 3 independent reviewers for 1,193 SLE and 1059 non-SLE patients. 500 randomly selected SLE and non-SLE patients formed the derivation cohort and the remainder the validation cohort.ResultsThe criteria were fine-tuned and simplified, using ANA of ≥1:80 as entry criterion and a classification threshold of 10.RenalClass III/IV nephritis10Class II/V nephritis8Proteinuria≥0.5 g/day4 Specific antibodiesAnti-Sm orAnti-dsDNA6Muco-cutaneousACLE6SCLE orDLE4Alopecia or oral ulcers2SerosaAcute pericarditis6Effusion5Musculo-skeletalArthritis6CNSSeizures5Psychosis3Delirium2BloodAutoimmune hemolysis or thrombocytopenia4Leukopenia3ComplementLow C3 and C44Low C3 or C43Anti-phospholipidAnti-Cardiolipin or anti-β2-GPI or lupus anticoagulant2ConstitutionalFever2Sensitivity was close to the SLICC 2012 criteria, specificity maintained at the level of the ACR 1997 criteria. This performance was independently confirmed in the validation cohort.ACR 1997 criteriaSLICC criteriaNew criteria DerivationSensitivity84.6396.8198.00Specificity95.2090.0096.40ValidationSensitivity82.7696.7096.12Specificity93.3883.6293.38ConclusionsThe new criteria developed with EULAR/ACR support achieved sensitivity close to the SLICC criteria, while maintaining the specificity of the ACR criteria.References[1] Aringer, et al. Ann Rheum Dis2017;76(S2):4.[2] Tedeschi, et al. Ann Rheum Dis2017;76(S2):50.Disclosure of InterestNone declared

Takayasu arteritis (TA) is difficult to diagnose because diagnostic biomarkers have not yet been established. In a previous study, we detected autoantibodies against the human ferritin heavy chain protein (HFC) in the sera of patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR). The aim of this study is to evaluate the frequency of autoantibodies against HFC in TA. We established seven ELISA assays for the detection of autoantibodies against HFC. We used the full-length recombinant HFC expressed in Escherichia coli or one of six different HFC peptides as autoantigens: 1-18Aa (98.8 % purity), 19-45Aa (98.8 % purity), 52-78Aa (98.3 % purity), 79-104Aa (98.8 % purity), 105-143Aa (98.4 % purity) and 145-183Aa (98.5 % purity). We collected sera from 48 patients with TA, 36 patients with systemic lupus erythematosus (SLE), 35 patients with arteriosclerosis, 133 patients with febrile diseases, which are known to generate unspecific autoantibodies, and 50 blood donors, which served as controls. The best results were obtained using the ferritin peptides as antigens. By combining the results from the different ELISAs that detect autoantibodies against the HFC peptides 19-44A, 79-104A and 105-144A, we were able to detect ferritin peptide antibodies in 30/48 (62 %) of the TA patients. The frequency was lower than in early GCA and PMR (previous study showed up to 92 %). Positive results were observed in 0/50 (0 %) of the control blood donors, 10/36 (28 %) of the SLE patients, 4/35 (11 %) of the arteriosclerosis patients and 27/133 (20 %) of the fever patients. Considering the lack of biomarkers for TA, autoantibodies against HFC peptides could act as useful markers for TA.

Systemic lupus erythematosus (SLE) is a chronic systemic intermittent autoimmune disease, which can affect nearly all organ systems. The disease is characterized by the detection of more than 100 different auto-antibodies. For the clinical practice as well as in controlled clinical studies it is absolutely necessary to define target criteria which allow the evaluation of the effectiveness of therapy. Many instruments are available for measuring the activity of the disease, the quality of life, the extent of irreversible damage and the individual manifestation in organs. There are also now various biomarkers to characterize the pathophysiologic aspects, clinical activity, therapeutic effectiveness and prognosis.

Objectives The proteasome inhibitor bortezomib, approved for the therapy of multiple myeloma, depletes plasma cells (PCs) and ameliorates nephritis in mouse models of systemic lupus erythematosus (SLE). Here, we analyzed the efficacy of bortezomib as induction therapy in patients with refractory SLE. Methods Twelve patients with active SLE were included in this prospective multicentre cohort study. The patients received one to four cycles of intravenous bortezomib (Velcade®) 1.3mg/m2 as “off-label” treatment. Disease activity was evaluated using the SELENA-SLEDAI score. We determined serum concentrations of anti–double-stranded DNA (anti-dsDNA) and protective antibodies. Multicolor flow cytometry was performed to analyze peripheral blood B and PC subsets as well as Siglec-1 expression on monocytes as surrogate marker for type I interferon (IFN) activity. Results The disease activity significantly decreased upon induction therapy with bortezomib and remained stable for the following 3 months under maintenance therapies. Treatment-related adverse events were mild or moderate. During proteasome inhibition, serum antibody concentrations significantly declined with greater reductions in anti-dsDNA (∼60%) than protective (∼30%) antibodies. Upon bortezomib treatment, numbers of HLA-DR+ short-lived (p=0.024) and HLA-DR– long-lived (p=0.038) peripheral blood PCs were strongly decreased, whereas circulating B cells remained virtually unaffected. Notably, PC numbers significantly increased in-between cycles. Siglec-1 expression on monocytes significantly declined (p<0.001) indicating reduced type 1 IFN activity. Conclusions Bortezomib targeting PCs and type I IFN activation may represent an effective treatment option with rather low toxicity in refractory SLE patients. Bortezomib efficiently induces short-term remissions but requires maintenance treatment inhibiting PC regeneration for sustained efficacy. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5884