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Background:ANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology and the broad clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Unfortunately the clinical classification, ANCA specificity or genetic characteristics alone is not able to categorize AAV patients in a satisfactory manner. As a consequence advanced statistical techniques were used to identify and stratify AAV subphenotypes [1, 2]. Here we have analyzed influence of the ANCA type on clinical manifestations and demographic characteristics in various types of AAV, based on data from the POLVAS registryObjectives:We decided to retrospectively analyze a large cohort of Polish AAV patients deriving from several referral centers – members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS) – and concentrate on demographic and clinical characteristics of anti-PR3 and anti-MPO positive patients regardless of their clinical diagnosis.Methods:We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016. Patients were enrolled by 9 referral centers. We analyzed dichotomous variables: gender; ANCA status – anti-PR3+ or anti-MPO+, ANCA negative; organ involvement - skin, eye, ENT, respiratory, heart, GI, renal, urinary, CNS, peripheral nerves and polytomous variable (number of relapses), supported by quantitative covariates (e.g., age at diagnosis, CRP at diagnosis, maximal serum creatinine concentration ever)[3].Results:MPO-positive patients (both GPA and EGPA phenotype) were older at the time of diagnosis with a substantial percentage diagnosed > 65 years of age, and with high rate of renal involvement. Interestingly, while in the whole group of patients diagnosed with EGPA male to female ratio was 1:2, the MPO+ EGPA patients showed M:F ratio of 1:1.The analysis of ANCA negative AAV reveled significant differences in GPA, ANCA negative group is characterized with significantly lower frequency of renal involvement compared to rest GPA (11,5% vs 63,7%) pConclusion:ANCA specificity is indispensable as a separate variable in any clinically relevant analysis of AAV subcategories. MPO+ group is characterized by older age at time of diagnosis, male to female ration 1:1, kidney involvement, and shows more homogenous clinical phenotype than PR3+ AAV patients. In our group ANCA negative AAV never lead to ESRD (end stage renal disease) or even transient dialysis.References:[1]Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatol Oxf Engl 2019;58:1707–9. https://doi.org/10.1093/rheumatology/kez148.[2]Wójcik K, Biedroń G, Wawrzycka-Adamczyk K, Bazan-Socha S, Ćmiel A, Zdrojewski Z et al. Subphenotypes of ANCA-associated vasculitis identified by latent class analysis. Clin Exp Rheumatol. 2020 Sep 1. Epub PMID: 32896241.[3]Wójcik K, Wawrzycka-Adamczyk K, Włudarczyk A, Sznajd J, Zdrojewski Z, Masiak A, et al. Clinical characteristics of Polish patients with ANCA-associated vasculitides—retrospective analysis of POLVAS registry. Clinical Rheumatology. 1 wrzesień 2019;38(9):2553–63.Disclosure of Interests:None declared

Background:Rituximab (RTX) is a B cell depleting monoclonal antibody with proven efficacy in the treatment of ANCA-associated vasculitis (AAV). The infectious complications occur in 15-25%.Objectives:We aimed to assess the frequency and risk factors of infections in patients with AAV receiving RTX among Polish patients.Methods:7 tertiary referral centers experienced in the treatment of vasculitis completed a questionnaire regarding AAV patients treated with RTX.Results:Among 49 patients included in the analysis (47 with GPA, 2 with MPA; 36/73% men; mean age at diagnosis 42,45±14,9 yrs., mean age on RTX initiation 46,14±14,72 yrs.,) at least one infection occurred in 20 patients (40.82%) after mean time of 16,65±16,01 weeks since the administration of RTX. Patients were followed for a mean time of 26,88±21,94 months. There were no differences in the incidence of infectious complications by gender, age, BMI, smoking status, severity of the disease, activity of the disease (BVAS), time from diagnosis to RTX initiation, carriage of staphylococcus aureus in the upper respiratory tract, total dose of CYC before RTX treatment. We didn’t observe severe hypogammaglobulinemia or neutropenia after RTX treatment. 40% of the observed infections occurred during the first month, 35% between second and sixth month of follow-up, while 25% were observed between 6 and 12 months after the RTX initiation. Of the 20 patients who developed infection, 12 (24.5%) had further infections. Antibiotic prophylaxis with trimethoprim–sulfamethoxazole was administered in 40 out of 49 (81.63%). Upper respiratory tract infection was the most common infectious complication (n=11), followed by lower respiratory tract (n=4), soft tissues (n=4) and urinary tract infections (n=4), lacrimal gland abscess (n=2) and abdomen (n=1). In cases with a positive microbial result Staphylococcus aureus (n=4), Klebsiella pneumoniae (n=2), Pseudomonas aeruginosa (n=1), Candida (n=1) and others (n=6) were identified. No fatalities were recorded and only 3 patients had severe infection with the necessity of prolonged treatment.Conclusion:Despite the high number of infections in our group treated with RTX, most of them were not severe. Upper respiratory tract was the most common site of infection.Disclosure of Interests:None declared

Background:ANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus there is an unmet need for phenotype identification especially among patients with granulomatosis with polyangiitis GPA, patients with microscopic polyangiitis MPA group seems to be more uniform. Recently, based on previous clustering analysis and clinical, histopathological, serological and prognostic aspects three subcategories of AAV have been proposed and named as: non-severe AAV, severe PR3-AAV and severe MPO-AAV [1].Objectives:In line with these attempts to subcategorize AAV we decided to use latent class analysis (LCA) on a large multicenter cohort of polish AAV patients from POLVAS [2] registry to identify potential new subphenotypes or confirm already proposed ones.Methods:Latent Class Analysis (LCA) approach was used as a model based clustering method of objects described by dichotomous (e.g., gender; ANCA status – cANCA, pANCA; organ involvement - skin, eye, ENT, respiratory, heart, GI, renal, urinary, CNS, peripheral nerves) and polytomous (number of relapses) variables supported by quantitative covariates (e.g., age at diagnosis, CRP at diagnosis, maximal serum creatinine concentration ever).Results:Results of LCA on our AAV group returned four class model of AAV subphenotypes, confirming existence of the previously proposed by Mahr at al. [1] and revealed fourth – previously not described clinically relevant subphenotype. To this fourth class - belong patients only with GPA, diagnosed at young age, with multiorgan involvement, high relapse rate and relatively high risk of death.Table 1.AAV subcategorization – summary of clinical characteristics and ANCA specificityLCA Class 1LCA Class 2LCA Class 3LCA Class 4No of patients13019410297AAV typeMainly GPAMainly GPAmainly MPAOnly GPAAge at diagnosisMiddle ageMiddle ageOldYoungMale/female ratio1:22:11:11:1Main organ involvementENT, respiratory, eyeRenal, respiratory, ENTRenal, respiratory, skinMultiorgan involvementRelapse rateintermediateintermediatelowhighModified class description (based on ref. [1])Non severe AAVSevere PR3 AAVSevere MPO AAVSevere non-renalPR3 AAVConclusion:Based on multiple clinical and serological variables LCA methodology identified 4-class subphenotypes model of AAV. Fourth-class is a new clinically important subphenotype including exclusively PR3-positive young AAV patients with multiorgan involvement, high risk of relapse and distinct mortality.References:[1]Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatol Oxf Engl 2019;58:1707–9.https://doi.org/10.1093/rheumatology/kez148.[2]Wójcik K, Wawrzycka-Adamczyk K, Włudarczyk A, Sznajd J, Zdrojewski Z, Masiak A, i in. Clinical characteristics of Polish patients with ANCA-associated vasculitides—retrospective analysis of POLVAS registry. Clinical Rheumatology. 1 wrzesień 2019;38(9):2553–63.Disclosure of Interests:Krzysztof Wójcik: None declared, Adam Ćmiel: None declared, Anna Masiak: None declared, Zbigniew Zdrojewski: None declared, Radoslaw Jeleniewicz: None declared, Maria Majdan Consultant of: Roche, Amgen, Speakers bureau: Roche, Amgen, Iwona Brzosko: None declared, Marek Brzosko: None declared, Piotr Głuszko: None declared, Małgorzata Stasiek: None declared, Małgorzata Wisłowska: None declared, Joanna Kur-Zalewska: None declared, Marta Madej: None declared, Anna Hawrot-Kawecka: None declared, Hanna Storoniak: None declared, Barbara Bułło-Piontecka: None declared, Alicja Dębska-Ślizień: None declared, Eugeniusz Kucharz: None declared, Katarzyna Jakuszko: None declared, Jacek Musiał: None declared

Background:Orbital inflammatory masses have been described as the common manifestation of granulomatosis with polyangiitis (GPA) occuring in 7- 45% of patients.Objectives:Identification and characterization of patients with orbital pseudotumor among Polish patients based on the national vasculitis registry, POLVAS.Methods:Clinical presentation and management of all GPA patients fulfilling ACR criteria or Chapel Hill Consensus Conference definition included to the Polish registry POLVAS who developed orbital masses in the course of GPA were evaluated.Results:Ocular involvement was found in 114 (27%) of 417 GPA patients registered in POLVAS, 34 (8%) developed orbital masses. Mean patients’ age was 47.8 (range from 19-75) yrs., 23 (67%) were women. Forty four per cent of the patients developed tumor at the beginning of the disease, 56% during relapse. Patients’ characteristics on diagnosis of orbital mass: 24 cANCA, 2 pANCA, and 8 ANCA negative, 9% active smokers and 31% past smokers, 29% had localized disease, 21% early systemic and 50% systemic with organ involvement, 29% had other type of ophthalmological involvement before pseudotumor occurred, 88% had active paranasal sinus involvement, 41% lungs, 15% CNS, 15% skin and 6% heart manifestations. Thirty seven per cent of patients had positive nasal swabs cultures, 50% of which were positive for Staphylococcus aureus. In 65%, tumor occurred during steroid therapy (46% had prednisone more than 5mg/d) and 45% on immunosuppressive treatment (19% when treated with AZA, 16% MTX, 6,5% MMF and 3,5% CYC). Due to orbital mass 86.5% were treated with CYC and 13.5% with RTX. Twenty one per cent had complete remission of the pseudotumor, 76% partial remission and in 3% patients there was no response to the treatment; 43% developed visual impairment, 20% suffered from blindness.Conclusion:Orbital inflammatory mass was not common manifestation of GPA among our patients. The mass developed at the beginning or in the course of the disease, even during immunosuppressive treatment. Orbital masses have been resistant to therapeutic interventions and were accompanied by high risk of visual impairment.Disclosure of Interests:Anna Masiak: None declared, Marcin Ziętkiewicz: None declared, Krzysztof Wójcik: None declared, Katarzyna Wawrzycka-Adamczyk: None declared, Radoslaw Jeleniewicz: None declared, Marta Madej: None declared, Joanna Kur-Zalewska: None declared, Katarzyna Jakuszko: None declared, Małgorzata Wisłowska: None declared, Hanna Storoniak: None declared, Michał Komorniczak: None declared, Barbara Bułło-Piontecka: None declared, Iwona Brzosko: None declared, Małgorzata Stasiek: None declared, Eugeniusz Kucharz: None declared, Alicja Dębska-Ślizień: None declared, Maria Majdan Consultant of: Roche, Amgen, Speakers bureau: Roche, Amgen, Jacek Musiał: None declared, Zbigniew Zdrojewski: None declared

Background Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) are strongly correlated with lupus anticoagulant. A Task Force of scientists at the International Congress on Antiphospholipid Antibodies (APLA 2010) accepted that aPS/PT would potentially contribute for a better identification of antiphospholipid syndrome (APS). Accordingly,we carried out an Initial and a Validation retrospective, cross-sectional multi-centre study on aPS/PT. Objectives To ascertain the value of aPS/PT for APS diagnosis. Methods We conducted an initial study involving 8 centres from 7 countries.Demographics and clinical/laboratory data were retrospectively collected.A sample from the subjects was prepared at each institution.Specimens were blinded and determination of IgG aPS/PT performed at Inova Diagnostics, Inc.USA (Inova) using ELISA kits from two manufacturers:Medical and Biological Laboratories Co Ltd, Japan (MBL) and Inova.After completing the initial study, a Validation study with a new sample of subjects (5 different centres from 5 countries) was carried out using the same methodology. Results The Initial study comprised 247 subjects.Statistically significant correlation in the IgG aPS/PT values was obtained with both ELISA kits (r=0.827, p Conclusions The performance of IgG aPS/PT using Inova and MBL ELISA kits is reliable. IgG aPS/PT detection is an easily performed laboratory parameter that may help in the diagnosis of APS. Acknowledgements The authors want to acknowledge the contributions of the late Prof. Silvia Pierangeli, University of Texas Medical Branch, Galveston, TX, USA Disclosure of Interest O. Amengual: None declared, R. Forastiero: None declared, M. Sugiura-Ogasawara: None declared, K. Otomo: None declared, O. Kenji: None declared, C. Favas: None declared, J. Delgado Alves: None declared, P. Žigon: None declared, A. Ambrožic: None declared, M. Tomsic: None declared, I. Ruiz Arruza: None declared, G. Ruiz Irastorza: None declared, M. Bertolaccini: None declared, G. Norman Employee of: Inova Diagnostics, Inc, San Diego, CA USA, Z. Shums: None declared, A. Jiro Employee of: Medical and Biological Laboratories, Co. Ltd, A. Murashima: None declared, A. Tebo: None declared, M. Gerosa: None declared, P. Meroni: None declared, I. Rodriguez-Pintό: None declared, R. Cervera: None declared, J. Swadzba: None declared, J. Musial: None declared, T. Atsumi Grant/research support from: Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Bristol-Myers Squibb Co., Astellas Pharma Inc., Daiichi Sankyo Co., Ltd. and Mitsubishi Tanabe Pharma Co., Speakers bureau: Astellas Pharma Inc. and Mitsubishi Tanabe Pharma Co.

Background Defective function of regulatory T cells (Treg) leads to the impairment of immune tolerance implicated in the pathogenesis of autoimmune inflammation in systemic lupus erythematosus (SLE). Methods To investigate the role of Treg in SLE we studied peripheral blood Treg and CD4+ effector T-helper cells (Th1, Th17), expression of their signature cytokines by in vitro activated lymphocytes (real-time PCR), and levels of TGF-β1, IL-10 and IL-17A (ELISA) in sera from patients with active–SLE (n=13), inactive-SLE (n=13) and matched healthy subjects (n=13). Results There was a significant decrease in CD4+ lymphocyte count in active SLE, with no evident difference in the percentage of CD25+FoxP3+ Treg cells as compared to other groups. Treg absolute counts decreased significantly in active-SLE (∼2-fold as compared to controls) and weakly correlated with markers of disease activity (C4, r=0.44). Only Th1 (IFN-γ producing) cells, but not Th17 (IL-17A producing) cells decreased in active disease, resulting in lower Th1/Th17 ratio. This was confirmed by a lower expression of IFN-γ mRNA (but not IL-17A) in peripheral blood lymphocytes from patients with active-SLE. All patients with SLE were characterized by lower Treg/Th17 ratio (median 1.4 vs. 2.4 in controls, p Conclusions Our data suggest, that SLE associated lymphopenia affects primarily Treg and Th1, but not Th17 fraction, resulting in imbalance between regulatory and effector CD4+ subsets. This may lead to relative deficiency in suppressive function of Treg (as evidenced by decrease in TGF-β1), and consequently to the increased proinflammatory response during active phase of the disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3602

Background Granulomatosis and polyangiitis (GPA) is a systemic vasculitis associated with anti-proteinase-3 antibodies and T-cell activation. Recruitment of memory T-cells into inflammatory sites depends on chemokine receptors and their specific patterns shape functional properties (e.g. cytokine production) of T helper-cells. Methods We analyzed subtypes of peripheral blood CD4+ memory (CD45RA-) T-cells identified by the expression of CCR7, CXCR3, CCR4, CCR6 and CCR10 chemokine receptors (multicolor flow cytometry) in GPA patients (n=20, 3 with active disease) and age matched healthy controls (n=18). Results GPA patients showed decreased percentage of CD4+ naive cells (mean 20,8 vs. 44,4% in controls) and increased fraction of CD45RA-CCR7- effector memory cells (33,8 vs. 19,2%). A significant increase in the percentage of CXCR3+, CCR4+ and CCR6+ (but not CCR10+) CD4+ cells was also observed. When analyzing co-expression of chemokine receptors, we were able to identify 16 different subpopulations of CD4+ memory T-cells, with only CCR6+ subtypes elevated in GPA. Of note, in GPA we found significant increase in the frequency of CXCR3+CCR4-CCR6+CCR10- CD4+ cells (Th1Th17-like, 13,6 vs. 9,7% in controls) and CXCR3-CCR4+CCR6+CCR10- CD4+ cells (Th17-like, 11,2 vs. 6,4% in controls). The latter subtype was also significantly elevated in analysis limited to CD45RA- cells. Differences in CCR6+ fraction were most evident in patients with lung involvement and in those treated with low dose GCS ( Conclusions We show that CD4+ cells in GPA patients are switched towards effector memory phenotype, possibly as a signature of disease-related immune activation. We also found expanded CCR6+CCR10- subsets suggesting the involvement of Th1Th17-like and Th17-like cells in the pathogenesis of the disease. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3614

Background At present we use modified classification criteria (Sydney 2006) for a diagnosis of antiphospholipid syndrome (APS) (1). These criteria do not include IgA class anticardiolipin (aCL) or antiβ2-glycoprotein I (antiβ2GPI) antibodies. However, some data indicate an association of these antibodies with APS obstetrical complications. Moreover, IgA antiβ2GPI antibodies have been associated with thromboembolic events in patients with systemic lupus erythematosus (SLE) (3). Objectives We assessed a group of APS patients with arterial (stroke, transient ischaemic attack and myocardial infarction) and venous thromboembolic events and/or obstetric complications and their association with antiphospholipid antibody profile. Methods We enrolled a group of 128 APS patients - 43 with primary (PAPS) and 85 with secondary (SAPS) - into the study. In the SAPS group 74 patients were diagnosed with SLE and 11 – with SLE-like syndrome. ACL and antiβ2-GPI antibodies in 3 classes (IgG, IgM and IgA) were determined using enzyme-linked immunosorbent assay (QUANTA Lite aCL, aβ2GPI ELISA; INOVA Diagnostics, USA). Lupus anticoagulant (LA) was assessed according to SSC 2009 guidelines (4). Statistical analyses were performed using STATISTICA software. Results We observed a positive correlation between aCL IgA and arterial thrombosis in the SAPS group only (the coefficient of correlation [Phi] =0,36, p=0,003). We also observed a weaker correlations between arterial events and LA (Phi=0,22; p=0,04) and aCL IgG (Phi=0,29; p=0,01). These associations were not found in the PAPS group. Antiβ2-GPI antibodies did not correlate with arterial thrombosis. We did not find any significant correlations between antibodies studied and venous thrombosis, or obstetrical complications. Conclusions It seems that the evaluation of IgA aCL in addition to IgG and IgM classes might add some information to the thrombotic risk assessment in patients with APS secondary to SLE. References Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4:295-306. Carmo-Pereira S, Bertolaccini ML, Escudero-Contreras A, Khamashta MA, Hughes GRV. Value of anticardiolipin and anti-beta2-glycoprotein I antibody testing in patients with pregnancy morbidity. Ann Rheum Dis 2003; 62: 640-643. Mehrani T, Petri M. Association of IgA Anti-beta2 glycoprotein I with clinical and laboratory manifestations of systemic lupus erythematosus. J Rheumatol 2011; 38: 64-68. Pengo V., Tripodi A., Reber G., Rand T., Ortel L., Galli M., DeGroot P.G. Update of the guidelines for lupus anticoagulant detection. Official communication of the SSC. J Thromb Haemost. 2009; 7: 1737-1740. Disclosure of Interest None Declared

Background Conventional risk factors of coronary artery disease fail to explain accelerated atherosclerosis in systemic lupus erythematosus (SLE) patients. Clinical and experimental studies shows that soluble intercellular adhesion molecule 1 (sICAM-1) and von Willebrand factor (vWF) levels reflect endothelial damage or dysfunction. Objectives This study was conducted to determine the possible influence of endothelial pathology assessed by sICAM-1 and vWF levels on coronary artery calcifications in SLE patients. Methods In 60 SLE patients in stable clinical conditions, without a prior history of coronary artery disease, MultiDetector Computed Tomography (MDCT)-based coronary calcium scoring was performed. Laboratory evaluation included serum concentrations of sICAM-1, vWF, C-reactive protein (CRP) and antinuclear antibodies (ANA) titers. Results MDCT revealed coronary calcifications in 15 (25%) patients. Calcium scores ranged from 0.3 to 843.2 (median 31,7). No association was found between these scores and conventional coronary artery disease risk factors (obesity, hypertension, tobacco use, hyperlipidaemia, diabetes) nor CRP levels. On the contrary, as compared to patients with calcium score =0, in those with coronary calcifications higher concentrations of sICAM-1 (382.2±328.2 vs. 267.1±62.7, p=0.01), vWF (188.5±87.6 vs. 149.2±52.2, p=0.025) and higher ANA titers (8320±4521 vs. 4668±2717, p=0.03) were found. Conclusions Conventional risk factors of coronary artery disease as well as markers of an ongoing inflammation do not show significant association with coronary artery calcifications in SLE patients. Calcified atherosclerotic plaques were observed mainly in patients with elevated levels of sICAM-1, vWF or high ANA titers. The sICAM-1 and vWF levels may serve as a possible risk marker of coronary calcifications and may have a prognostic importance. Disclosure of Interest None Declared