scholarly journals AB0012 ROLE OF IRF5 GENE ON THE PATHOGENESIS OF IMMUNOGLOBULIN-A VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1309.1-1310
Author(s):  
S. Remuzgo Martinez ◽  
F. Genre ◽  
V. Pulito-Cueto ◽  
D. Prieto-Peña ◽  
B. Atienza-Mateo ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Disease Onset ◽  
Immunoglobulin A ◽  
Type I ◽  
Research Support ◽  
Development Fund ◽  
European Regional Development Fund ◽  
Social Fund ◽  
Relevant Role ◽  
Immunoglobulin A Vasculitis

Background:Interferon signaling pathway plays a relevant role in autoimmunity. Genetic variants in theinterferon regulatory factor (IRF) 5gene, that encodes the major regulator of the type I interferon induction [1], have been related to the development of several inflammatory diseases [2].Objectives:To determine the influence ofIRF5on Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular disease.Methods:ThreeIRF5polymorphisms (rs2004640, rs2070197 and rs10954213) representative of 3 different haplotype blocks were genotyped in 372 Caucasian patients with IgAV and 876 sex and ethnically matched healthy controls.Results:No statistically significant differences between patients with IgAV and controls were observed when eachIRF5polymorphism was analyzed independently. Similarly, no statistically significant differences between patients with IgAV and controls were found whenIRF5polymorphisms were evaluated combined conforming haplotypes. Additionally, there were no statistically significant differences in genotype, allele and haplotype frequencies ofIRF5when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations.Conclusion:Our results do not support an influence ofIRF5on the pathogenesis of IgAV.References:[1]Nat Immunol 2011; 12: 231-8;[2]Arthritis Res Ther 2014; 16: R146.Acknowledgments:This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF).Disclosure of Interests:Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Verónica Pulito-Cueto: None declared, D. Prieto-Peña: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Leticia Lera-Gómez: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, María Jesús Cabero: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, Antonio Navas Parejo: None declared, Javier Sanchez Perez: None declared, Maximiliano Aragües: None declared, Esteban Rubio: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galindez: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Raquel López-Mejías: None declared

scholarly journals AB0011 INFLUENCE OF IL17A GENE ON THE PATHOGENESIS OF IMMUNOGLOBULIN-A VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1309.2-1309
Author(s):  
F. Genre ◽  
S. Remuzgo Martinez ◽  
V. Pulito-Cueto ◽  
D. Prieto-Peña ◽  
B. Atienza-Mateo ◽  
...  
Keyword(s):  
Disease Onset ◽  
Immunoglobulin A ◽  
Genetic Network ◽  
Vascular Pathology ◽  
Type I ◽  
Healthy Controls ◽  
Research Support ◽  
Development Fund ◽  
Social Fund ◽  
Immunoglobulin A Vasculitis

Background:Cytokines signaling pathway genes represent a key component of the genetic network implicated in the pathogenesis of Immunoglobulin-A vasculitis (IgAV) [1], an inflammatory vascular pathology.Interleukin (IL)17Ais a genetic risklocusfor autoimmune diseases, such as giant cell arteritis [2] and spondyloarthritis [3].Objectives:To determine the potential influence ofIL17Aon IgAV.Methods:FiveIL17Atag polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were genotyped in 360 Caucasian patients with IgAV and 1,003 sex and ethnically matched healthy controls.Results:No statistically significant differences between patients with IgAV and healthy controls were observed when eachIL17Agenetic variant was analyzed independently. Similarly, no statistically significant differences between patients with IgAV and healthy controls were found when the fiveIL17Apolymorphisms were evaluated combined conforming haplotypes. In addition, there were no statistically significant differences in genotype, allele and haplotype frequencies ofIL17Awhen patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations.Conclusion:Our results do not support an influence ofIL17Aon the pathogenesis of IgAV.References:[1]Autoimmun Rev 2018; 17: 301-15[2]Ann Rheum Dis 2014; 73: 1742-5[3]Mediators Inflamm 2018; 2018: 1395823.Acknowledgments:This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF).Disclosure of Interests:Fernanda Genre: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, D. Prieto-Peña: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Leticia Lera-Gómez: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, María Jesús Cabero: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, Antonio Navas Parejo: None declared, Diego de Argila: None declared, Maximiliano Aragües: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galindez: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Raquel López-Mejías: None declared

scholarly journals Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana Prieto-Peña ◽  
Sara Remuzgo-Martínez ◽  
Fernanda Genre ◽  
Verónica Pulito-Cueto ◽  
Belén Atienza-Mateo ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Disease Onset ◽  
Immunoglobulin A ◽  
Genetic Network ◽  
Signalling Pathway ◽  
Immune Mediated ◽  
Increased Risk ◽  
Genotype And Allele Frequencies ◽  
Immunoglobulin A Vasculitis

AbstractCytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

scholarly journals BAFF, APRIL and BAFFR on the pathogenesis of Immunoglobulin-A vasculitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana Prieto-Peña ◽  
Fernanda Genre ◽  
Sara Remuzgo-Martínez ◽  
Verónica Pulito-Cueto ◽  
Belén Atienza-Mateo ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Genetic Risk ◽  
B Lymphocyte ◽  
Genetic Variant ◽  
Disease Onset ◽  
Immunoglobulin A ◽  
Genetic Network ◽  
Immune Mediated ◽  
Genotype And Allele Frequencies ◽  
Immunoglobulin A Vasculitis

AbstractBAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.

scholarly journals Finansowanie ochrony zdrowia z funduszy strukturalnych Unii Europejskiej

2018 ◽  
pp. 127-144 ◽  
Author(s):  
Piotr Bromber
Keyword(s):  
Health Protection ◽  
General Description ◽  
Development Fund ◽  
Structural Funds ◽  
European Regional Development Fund ◽  
Financial Perspective ◽  
European Social Fund ◽  
Social Fund ◽  
External Sources ◽  
The Subject

Accepting the argument that the financial means dedicated to health protection are limited, the author of the paper emphasizes the need to use external sources of financing, in this case European Union structural funds. This paper attempts to answer the question of to what extent the sources from the European Regional Development Fund, and the European Social Fund, have influenced, or can influence the improved efficiency of the health protection system in Poland. The paper begins with the fundamental notions of health protection, the levels and forms of the delivery of health services, the subject range of the system (including the catalogue of beneficiaries), and the sources of finance. The most important (in the author’s opinion) current problems related to the organization and financing of health protection are also mentioned. Next, a general description of selected operating programs is presented with the examples of health protection projects financed from the structural funds that have already been implemented. The opportunities to fund these types of projects under the present financial perspective are also indicated. The subject matter of a detailed analysis presented in the paper concerns the Lubuskie province.

scholarly journals Cohesion policy after Brexit: the economic, social and institutional challenges

2017 ◽  
Vol 46 (4) ◽  
pp. 745-763 ◽  
Author(s):  
JOHN BACHTLER ◽  
IAIN BEGG
Keyword(s):  
Social Development ◽  
National Level ◽  
Cohesion Policy ◽  
Investment Funds ◽  
Development Fund ◽  
European Regional Development Fund ◽  
European Social Fund ◽  
Social Fund ◽  
The Uk ◽  
Institutional Challenges

AbstractSince 1988, when the current EU Cohesion Policy was introduced, it has played an influential role in setting priorities for policies aimed at dealing with the effects of European economic integration on regional and social disparities. Although, latterly, the amount of money spent in the UK through the European Structural and Investment Funds (ESIF) has declined, EU programmes have had a disproportionate effect on the design and implementation of UK policies shaping regional and local economic and social development. This paper starts by recalling how EU Cohesion Policy has functioned in the UK, then considers how Brexit may affect regional and social development and the need for a corresponding policy response, focusing on the sorts of policies currently supported by the European Regional Development Fund (ERDF) and the European Social Fund (ESF). The paper shows that filling the policy vacuum will be far from straightforward because complementary national policies and institutional frameworks have lacked consistency or coherence. It concludes by examining the wider policy issues arising from rethinking domestic policy outside the ESIF framework. The sub-national level, in particular, will need a fresh approach following Brexit.

Article 175 TFEU

2019 ◽  
Author(s):  
Leo Flynn
Keyword(s):  
Economic Policies ◽  
Financial Instruments ◽  
Investment Bank ◽  
Development Fund ◽  
Structural Funds ◽  
European Regional Development Fund ◽  
European Social Fund ◽  
Social Fund ◽  
European Investment ◽  
European Regional

Article 159 EC Member States shall conduct their economic policies and shall coordinate them in such a way as, in addition, to attain the objectives set out in Article 174. The formulation and implementation of the Union’s policies and actions and the implementation of the internal market shall take into account the objectives set out in Article 174 and shall contribute to their achievement. The Union shall also support the achievement of these objectives by the action it takes through the Structural Funds (European Agricultural Guidance and Guarantee Fund, Guidance Section; European Social Fund; European Regional Development Fund), the European Investment Bank and the other existing Financial Instruments.

scholarly journals The mechanism of community led local development in Romanian urban areas

2020 ◽  
Vol 13 (2) ◽  
pp. 129-146
Author(s):  
Andreea Pușcaș ◽  
Ioana Beleiu
Keyword(s):  
Rural Areas ◽  
Urban Areas ◽  
Social Innovation ◽  
Local Development ◽  
Territorial Development ◽  
Development Fund ◽  
Positive Effects ◽  
European Regional Development Fund ◽  
Social Fund ◽  
Programming Period

Community led local development (CLLD) is a tool of the European Commission, used for territorial development. Local Action Groups were funded in the rural areas of Romania, since the 2007-2013 programming period through LEADER, demonstrating positive effects in terms of social innovation and disproof of social disparities. In urban areas, CLLD is a recent multi-fund approach, financed by the European Social Fund (ESF) and the European Regional Development Fund (ERDF). Despite the intentions addressed for simplifying the implementation of the mechanism by the Romanian authorities, several challenges and delays however occurred. The present research reveals the similarities and the main differences between the implementation of the mechanism, in urban and rural areasesides, it proposes a set of recommendations to increase the efficiency of the studied mechanism, based on a case study on the implementation of the CLLD mechanism in Gherla, Romania.

scholarly journals Assessment of changes in the level of human capital in Poland in the context of the use of European funds for projects in the field of science and education contracted for implementation in 2004–2006

2019 ◽  
pp. 5-22
Author(s):  
Małgorzata Sikora-Gaca ◽  
Urszula Kosowska
Keyword(s):  
Human Capital ◽  
Development Fund ◽  
Development Indicators ◽  
Structural Funds ◽  
European Regional Development Fund ◽  
Social Fund ◽  
Science And Education ◽  
Regional Leaders ◽  
Capital Development ◽  
The Impact

The article presents the analysis of 2,947 projects in the area of science and education co-financed by the Structural Funds in Poland in 2004–2006. It summarizes the investments co-financed by the European Regional Development Fund, the European Social Fund and the European Agricultural Guidance and Guarantee Fund. Data on 2,947 projects, with their regional division, have been verified. Thanks to this regional leaders have been distinguished in terms of the number of projects and raised funds in 2004–2006. Most importantly, the amount of the subsidy from the EU to projects in the area of science and education in Poland in the years 2004–2006 has been estimated per capita of individual region. These data were compared with the selected human capital development indicators in 2003, 2006, 2009 and 2012 to assess the impact of European funding in the field of science and education on human capital in Poland.

scholarly journals AB1059 A RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ANAKINRA IN PATIENTS WITH STILL´S DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1819.2-1820
Author(s):  
L. Schanberg ◽  
P. Nigrovic ◽  
A. Cooper ◽  
W. Chatham ◽  
S. Akoghlanian ◽  
...  
Keyword(s):  
Early Onset ◽  
Disease Onset ◽  
Study Drug ◽  
Placebo Patient ◽  
Controlled Study ◽  
Symptom Duration ◽  
Newly Diagnosed ◽  
Still’S Disease ◽  
Research Support ◽  
Still's Disease

Background:Adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) are rare autoinflammatory disorders associated with an activated IL-1 pathway, characterized by spiking fever, rash, arthritis, lymphadenopathy, hepatosplenomegaly and serositis. There is a growing understanding that SJIA and AOSD are one disease with different ages of onset, i.e. Still’s disease. The anaSTILLs study (anakinra inStill´sdisease) was designed to further evaluate efficacy and safety of anakinra in patients with Still´s disease across all age groups.Objectives:The primary objective was to demonstrate efficacy of anakinra versus placebo as assessed by ACR30 response with absence of fever at Week 2. Secondary objectives included: early onset of efficacy, sustained efficacy, time to study drug discontinuation, safety, pharmacokinetics, clinical signs and biomarkers.Methods:‘anaSTILLs’ was a randomized, double-blind, placebo-controlled, 12-week study including patients with active and newly diagnosed (6 months) Still´s disease according to adapted ILAR criteria if <16, or Yamaguchi criteria, if ≥16 years of age at disease onset. Patients were randomized to anakinra 2 mg/kg (max 100 mg/day), 4 mg/kg (max 200 mg/day) or placebo.Results:12 patients were randomized and received study drug: 6 anakinra (2 mg/kg n=2, 4 mg/kg n=4) and 6 placebo, the study was terminated early due to slow recruitment. 1 patient on placebo had lymphoma, not Still’s disease, and was excluded; thus in total 11 patients were analyzed for efficacy, 8 were children [median (range) age=4.0 (1-11) years] and 3 were adults [median (range) age=32.0 (25-51) years]. 55% were male and the mean symptom duration was 74.2 days. All patients on anakinra but none on placebo achieved ACR30 response with absence of fever at Week 2 (p-value=0.0022). The efficacy of anakinra was further demonstrated by superiority to placebo in ACR50/70/90 responses with absence of fever at Week 2. All placebo patients discontinued the study within 6 weeks, 2 due to progressive disease, 2 due to lack of efficacy and 1 due to withdrawal by patient. There was a numerically higher proportion with early onset of efficacy (Week 1) in the anakinra group compared to placebo. The ACR30/50/70/90 responses in the anakinra group were sustained throughout the study period. Patients in the anakinra group had a prompt and persistent decrease in CRP and ferritin levels at Week 1, which was not observed in the placebo group. There were no unexpected safety findings. All anakinra patients developed anti-drug antibodies (ADAs) at some timepoint during the study. ADAs were persistent throughout the treatment period, except in one patient. Titers were low to moderate. One placebo patient had low ADA titers at one occasion. No neutralizing antibodies were observed and the ADAs did not appear to impact clinical efficacy or safety.Conclusion:Anakinra is superior to placebo in the treatment of Still’s disease. ADAs occur frequently but do not appear to adversely impact efficacy or safety. These results confirm the benefits of anakinra treatment in patients with active, newly diagnosed Still´s disease across ages.Disclosure of Interests:Laura Schanberg Grant/research support from: Sobi, BMS, Consultant of: Aurinia, UCB, Sanofi, Peter Nigrovic Grant/research support from: Novartis, BMS, Pfizer, Consultant of: Novartis, BMS, Pfizer, Sobi, Miach Orthopedics, Simcere, XBiotech, Quench Bio, Ashley Cooper: None declared, Winn Chatham Grant/research support from: Sobi, Consultant of: Sobi, Shoghik Akoghlanian: None declared, Namrata Singh: None declared, Egla Rabinovich Grant/research support from: AbbVie, UCB Pharma, Janssen Research & Development, Akaluck Thatayatikom: None declared, Alysha Taxter: None declared, Jonathan Hausmann Consultant of: Novartis, Milan Zdravkovic Shareholder of: Sobi, Employee of: Sobi, Sven Ohlman Shareholder of: Sobi, Employee of: Former employee of Sobi, Henrik Andersson Employee of: Sobi, Susanna Cederholm Shareholder of: Sobi, Employee of: Sobi, Margareta Wikén Shareholder of: Sobi, Employee of: Former employee of Sobi, Rayfel Schneider Grant/research support from: Roche, Novartis, Sobi, Pfizer, Consultant of: Sobi, Novartis, Novimmune, Fabrizio De Benedetti Grant/research support from: AbbVie, Pfizer, Novartis, Novimmune, Sobi, Sanofi, Roche, Speakers bureau: AbbVie, Novartis, Roche, Sobi

scholarly journals THU0351 MUSCLE INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS AND ANTI-PM/SCL+ ANTIBODIES IS ASSOCIATED WITH CARDIAC AND PULMONARY INVOLVEMENT. ANALYSIS OF THE MULTICENTRE EUSTAR COHORT.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 407.1-407
Author(s):  
M. G. Lazzaroni ◽  
S. Zingarelli ◽  
P. Airò ◽  
Y. Allanore ◽  
O. Distler
Keyword(s):  
Systemic Sclerosis ◽  
Cardiac Involvement ◽  
Severe Disease ◽  
Disease Onset ◽  
Pulmonary Involvement ◽  
Left Ventricular ◽  
Research Support ◽  
Muscle Involvement ◽  
Group A ◽  
Tendon Friction Rubs

Background:Anti-PM/Scl antibodies positivity has been associated with frequent skeletal muscle involvement in patients with Systemic Sclerosis (SSc) in different studies, including the EUSTAR cohort (1). Moreover, although myositis has been previously associated with heart involvement in SSc patients (2), this issue has never been explored among anti-PM/Scl+ patients.Objectives:To evaluate the cardiac involvement in anti-PM/Scl patients with SSc in the large multicentre EUSTAR database, with focus on the subgroup of patients with muscle involvement.Methods:Patients from the EUSTAR database were included when the item anti-PM/Scl was fulfilled in at least one visit.Results:Anti-PM/Scl status was available in 7,353 SSc patients from EUSTAR database: 295 were anti-PM/Scl+. After exclusion of 151 patients with multiple autoantibody positivity, 144 anti-PM/Scl + patients were compared with 7,058 anti-PM/Scl- patients. Among them, 3,120 (44.2%) were positive for ACA, 2,361 (33.5%) for anti-Topo I and 274 (3.88%) for anti-RNAP3.Regarding the specific cardiac outcomes, in the anti-PM/Scl+ as compared to the anti-PM/Scl- group, a decreased rate of elevated sPAP at ECHO was recorded (12.8% vs 25.0%, p:0.001), while no differences were observed in the frequency of conduction blocks (26.2% vs 23.7%, p:0.526), abnormal diastolic function (33.9% vs 36.4%, p:0.582), pericardial effusion (10.2% vs 10.9%, p:1.000) and LVEF ≤50% (4.76% vs 6.11%, p:0.818). In multivariate analysis, adjusted for age at disease onset, sex, and disease duration, the negative association of anti-PM/Scl with elevated sPAP was not confirmed (p:0.061).When comparing anti-PM/Scl+ patients with (n=47) and without (n=87) CK elevation, the former group had a higher frequency of conduction blocks (43.2% vs 17.5%, p:0.005; OR 95% CI 3.47, 1.51-7.97) and left ventricular dysfunction, both diastolic (45.6% vs 27.2%, p:0.050; OR 95% CI 2.25, 1.05-4.81) and systolic (LVEF ≤50% 13.3% vs 0%, p:0.018; OR 95% CI 16.8, 0.87-324). Moreover, anti-PM/Scl+ patients with CK elevation had significantly increased rate of lung fibrosis on HRCT (p:0.045), intestinal symptoms (p:0.017), joint contractures (p:0.045) and tendon friction rubs (p:0.034).Conclusion:In the largest series of anti-PM/Scl positive SSc patients so far reported, muscle involvement in anti-PM/Scl+ patients (defined as increased serum CK) seems to represent a marker of a more severe disease phenotype, including a higher frequency of cardio-pulmonary involvement.References:[1]Lazzaroni MG, et al. Ann Rheum Dis 2018. 77 (2), 421-2.[2]Follansbee WP, et al. Am Heart J 1993. 125: 194-203.Acknowledgments:Authors would like to thank the patients’ association GILS (Gruppo Italiano Lotta Sclerodermia) for the grant that supported the project.Disclosure of Interests:Maria Grazia Lazzaroni: None declared, Stefania Zingarelli: None declared, Paolo Airò: None declared, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

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