Search

BackgroundSince the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefits of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group).ObjectivesTo evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://brightoncollaboration.us/wp-content/uploads/2021/01/SO2_D2.1.2_V1.2_COVID-19_AESI-update-23Dec2020-review_final.pdf)MethodsThe first ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defined as at least one of the following: new manifestations attributable to disease activity, hospitalization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants.ResultsA cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren’s syndrome (SS,12%), idiopathic inflammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Danlos’s syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the first and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%).ConclusionThis preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the first month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.Table 1.AEs and disease exacerbations per diseaseDiagnosisPatients enrolled (%) (n=300)EAs after 1st and 2nd dose (%)Exacerbations (%)APS25714EDS45033IIM10527MCTD44225SS12598SLE44698SSC16492UCTD850-AcknowledgementsVACCINATE is a study promoted by the European Reference Network on rare and complex connective tissue diseases, ERN ReCONNET. This publication was funded by the European Union’s Health Programme (2014-2020)Disclosure of InterestsNone declared

BackgroundThe complement system is a key-player in the pathogenesis of systemic lupus erythematosus (SLE); its decreases correlate with disease activity and precedes flare. Since synthesis of complement proteins increase during gestational course, it is debated whether complement levels exert a prognostic role in pregnant women with SLE.ObjectivesWe performed a network meta-analysis to assess the prognostic role of complement in pregnant SLE women, to evaluate the possible role of complement fluctuations during pregnancies.MethodsData from available prospective studies (Jan 2002-Dec 2020) investigating pregnancies in at least 50 SLE patients, excluding miscarriages before 12 weeks, were pooled together. After a systematic literature search, corresponding authors of 19 retrieved studies meeting inclusion criteria were invited to contribute with additional data, including complement levels [6 months before pregnancy, at conception, 1st trimester (T1), 2nd trimester (T2), 3rd trimester (T3) and 3 months after delivery].ResultsA total of 532 SLE women from four eligible studies were included in the analysis [1-4]. Lupus Nephritis (LN) was diagnosed in 237 patients (44.5%) and Antiphospholipid Syndrome in 68 (12.8%). A total of 170 patients (32%) experienced a flare during pregnancy, defined as need of new Immunosuppressants or increase of prednisone > 9 mg/day.Patients with LN had significantly lower mean levels of complement (C3 at conception; C3 at T1; C3 after 3 months of delivery; C4 at all timepoints except for C4 at T3). SLE patients who experienced flares during pregnancy had significantly lower mean levels of complement (all timepoints for both C3 and C4). Table 1 shows the mean C3 and C4 levels in different timepoints according to diagnosis and flare during pregnancy. The lowest levels of complement were observed in patients with a concomitant diagnosis of LN and presence of flare, particularly during the T1 (Figure 1). Nevertheless, both in LN and flare groups the lowest levels of C3 and C4 were documented at T1.Table 1.Complement levels at the different timepoints according to diagnosis or presence of flare (bold results are statistically significant)Patients with LN(237)Patientswithout LN (295)Patients with Flare (170)Patients without Flare (362)Patients with LN and Flare (73)Patients with LN and without Flare (164)C3 6 months before pregnancy (mean ±SD)90.7±18.694.1±25.285.6±19.195.6±23.375 ±17.999.1±12.5C3 conception (mean ±SD)96.1±13.991.1±1395.3±19.591.8±9.197 ±21.695.6±7.1C3 1sttrimester (mean ±SD)84.6±32.298.4±14.178.3±22.8100.5±20.756.8 ±19.997.2±28.7C3 2ndtrimester (mean ±SD)108.5±21108.3±12.294.16±13.4115.7±12.387.5 ±10.9118.6±16.8C3 3rdtrimester (mean ±SD)105.5±15.7108.2±19.198.97±18.6111.4±1698.1 ±12.6109.1±15.8C3 3 months after delivery (mean ±SD)93.4±12103.1±15.492.4±15.7102.6±13.490.5 ±10.894.8±12.3C4 6 months before pregnancy (mean ±SD)15.7±5.514.1±2.811.8±3.916.5±3.310.5±3.418.4±4.2C4 conception (mean ±SD)15.4±4.113.9±2.813.3±3.215.7±3.411±1.317.8±3C4 1sttrimester (mean ±SD)15±7.816.3±2.812.5±5.917.5±4.29.3±7.617.9±6.2C4 2ndtrimester (mean ±SD)17.7±4.718.7±4.215.5±4.319.8±3.713.6±4.119.6±3.5C4 3rdtrimester (mean ±SD)17.8±4.417.5±5.115.7±5.818.6±415.8±4.818.8±3.9C4 3 months after delivery (mean ±SD)16.2±4.319.8±6.914.9±3.920±6.413.3±3.117.6±4Figure 1.Complement Levels during time in patients with Lupus Nephritis and presence, or absence, of flare.ConclusionIn this prospective large cohort of SLE patients low C3/C4 levels, particularly in T1, were associated with a higher frequency of flare. Lowering levels of complement, especially in T1, even within normal range might alert the treating clinicians in predicting disease course and consequently avoid flares, especially in LN.References[1]Saavedra MÁ et al. Int J Rheum Dis 2020[2]Moroni G et al. J Autoimmun 2016[3]Rodrigues BC et al. Lupus 2019[4]Borella E et al. Immunol Res 2014Disclosure of InterestsNone declared

BackgroundOver 80% of patients affected with SLE experience skin involvement. The anti-BLyS drug belimumab was shown effective in ameliorating mucocutaneous SLE manifestations in clinical trials and real-life studies. Cutaneous response is quantified through the CLASI (cutaneous lupus erythematosus area and severity index). Clinically relevant improvements are defined as decreases of ≥50% (CLASI50) or 70% (CLASI70) from baseline values.ObjectivesTo assess rates and predictors of CLASI50 and CLASI70 in the Berliss multicentric SLE cohort1 of patients treated with belimumab.MethodsBaseline and ongoing features of patients with baseline active skin involvement (CLASI>0) were assessed in relationship to the chosen outcomes CLASI50 and CLASI70 at 24 and 52 weeks. A subanalysis on patients with CLASI≥5 was as well conducted. Logistic regression was employed to identify predictors of response.Results172 patients displayed skin involvement at baseline (CLASI>0). Of those, 124 displayed at least a 12-month-follow-up and were included in the analysis. Seventy-seven (62.1%) patients reached CLASI50 at 24 weeks and 91 (77.8%) at 52 weeks; 87 (70.2%) reached CLASI70 at 24 and 99 (79.8%) at 52 weeks. Baseline predictors of CLASI50 at 24 weeks were CLASI-damage (CLASI-d) (OR [95%CI], p; 0.79 [0.65-0.98] 0.03) and disease duration (0.93[0.86-0.99], 0.011). No baseline predictors of CLASI70 at 24 weeks emerged, however having achieved a CLASI50 response at 24 weeks portended CLASI50 and 70 response through week 52 (pTable 1.Predictors of CLASI-A Response at Week 24 and 52 by Baseline CLASI-A at 50% and 70% Response ThresholdsTimepointOutcomeVariableOR[95%CI] pCLASI>024 weeksCLASI50CLASI-d0.79 [0.65-0.98] 0.030Disease duration0.93[0.86-0.99], 0.011CLASI70CLASI-d0.93 [0.74-1.16], 0.51Disease duration0.97 [0.97-1.02], 0.1852 weeksCLASI50CLASI50 at 24 weeks14.3[4.88-44.42], CLASI70CLASI50 at 24 weeks6.22 [2.00-19.34], 0.002CLASI≥524 weeksCLASI50CLASI-d0.72 [0.53-0.98], 0.037Disease duration0.93 [0.66-1.00], 0.071CLASI70Antimalarials6.61 [1.20-36.29] 0.032Smoking0.15 [0.03-0.83], 0.03452 weeksCLASI50CLASI50 at 24 weeks22.0 [2.47-196.05], 0.006CLASI70CLASI50 at 24 weeks1.24 [0.06-25.08], 0.88CLASI, cutaneous lupus erythematosus area and severity index; CLASI-d, CLASI damage; CLASI50 and CLASI70: decrease ≥50% or ≥70% in CLASI from baseline. OR and 95%CIs are estimated using a logistic regression model with stratification factors as covariates (SLEDAI-2K at baseline, baseline prednisone dosage).ConclusionEarlier use of belimumab favors achievement of skin response among SLE patients and attainment of a prompt response predicts further response. Use of antimalarials reinforces while smoking hampers a more profound CLASI improvement over time.References:[1]Gatto M, et al. Arthritis Rheumatol. 2020 Aug;72(8):1314-1324Disclosure of InterestsMariele Gatto Speakers bureau: GSK, Grant/research support from: GSK, Roberto Depascale: None declared, Angela Tincani: None declared, Giacomo Emmi: None declared, Salvatore Scarpato: None declared, Fabrizio Conti: None declared, Marcello Govoni: None declared, Marta Mosca: None declared, Maria Gerosa: None declared, Enrica Bozzolo: None declared, Valentina Canti: None declared, Armando Gabrielli: None declared, Elisa Gremese: None declared, Salvatore De Vita: None declared, francesco ciccia: None declared, Carlo Salvarani: None declared, Maurizio Rossini: None declared, Paola Faggioli: None declared, Antonella Laria: None declared, Amato De Paulis: None declared, Roberto Gerli: None declared, Enrico Brunetta: None declared, Alessandro Mathieu: None declared, Carlo Selmi: None declared, Rossella De Angelis: None declared, Simone Negrini: None declared, Margherita Zen: None declared, Andrea Doria Speakers bureau: GSK, Eli Lilly, Roche, Grant/research support from: GSK, Luca Iaccarino Speakers bureau: GSK, Grant/research support from: GSK

BackgroundPentraxin-3 (PTX3) seems to be implicated in placentation and foetus tolerance, being mostly secreted in response to inflammatory stimuli by dendritic cells, macrophages, and endothelial cells (1). Although several studies have recently focused on this molecule (2-4), no data on women with SLE/APS are available to date.ObjectivesTo assess the role of serum PTX3 and anti-PTX3 Abs as predictors of pregnancy complications in SLE and/or APS.MethodsThis case control study included pregnancies in women with SLE (SLICC, 2012) and/or APS (Miyakis, 2006), recruited at University of Padova in the Out-patient Clinic shared by Obstetrics and Gynaecologists and Rheumatologists. The control group included pregnancies of patients with other rheumatic diseases rather than APS and/or SLE. All pregnancies were recruited from 2015 to 2021 (conception date< 1st Apr 2021).At first-trimester consultation, demographics, clinical, and serological variables were recorded. First-trimester serum PTX3 levels (ng/ml) were detected by a commercially available sandwich ELISA (Alexis, UK); IgG anti-PTX3 Abs were detected by home-made validated ELISA and expressed as Optical Density values, measured at 405 nm by microplate spectrometer. Cut-off of positivity corresponded to 0.234 OD.Maternal complications included SLE flares (increase of ≥1 point in SLEPDAI); preeclampsia/eclampsia, HELLP, pregnancy induced hypertension, maternal death, gestational diabetes mellitus (GDM). Foetal complications included: miscarriageResults79 pregnancies occurred in 79 patients (Table 1). Serum IgG anti-PTX3 Abs were found in 11 women (13.9%, 95% CI 7.2-23.5), and they did not differ between cases and controls (p=0.08, 4 SLE/APS women vs. 7 controls). Anti-PTX3 were associated with GDM (p=0.04, stratified for maternal age) but not with IUGR (p=0.09). No other statistical associations were found between anti-PTX3 Abs and other maternal/foetal complications. PTX3 serum levels did not statistically differ between cases and controls (p=0.63, 0.37 ± 0.26 ng/mL in cases vs. 0.33 ± 0.24 ng/mL in controls). Serum PTX3 levels were lower in patients with GDM (0.3 ± 0.2 ng/mL) compared to non-GDM patients (0.4 ± 0.2) but it did not differ between IUGR and non-IUGR, although the mean PTX3 ± SD was lower in the IUGR group (0.25 ± 0.2 in IUGR vs 0.35 ± 0.2 in non-IUGR).Table 1.Clinical and serological characteristics of our cohort (N=79)Patients (N, %)Age at pregnancy, years (mean ± SD)35.1 ± 3.9Cases13 (16.5)SLE9 (11.4)APS7 (8.9)SLE with secondary APS3 (23.1)Control Group66 (83.5)Serological featuresLAC11 (13.9)IgG/IgM anti-cardiolipin20 (25.3)IgG/IgM antibeta2-Glycoprotein I25 (31.6)Triple positive aPL tests6 (7.6)Primiparous23 (29.5)IgG anti-PTX3 Abs11 (13.9)IgG anti-PTX3 level (cut-off 0.234 OD), (median, IQR)0.2 (0.1-0.2)PTX3 ng/mL (mean ± SD)0.3 ± 0.2Concomitant treatmentHeparin15 (19.0)Aspirin44 (55.7)Immunosuppressants3 (3.8)Hydroxychloroquine21 (26.6)Prednisone9 (11.4)Prednisone dosage (mg/day) (median, IQR)5 (2.5-7.5)Legend to Table 1: SD: standard deviation; SLE: Systemic Lupus Erythematosus; APS: antiphospholipid syndrome; LAC: Lupus anticoagulant; aPL: antiphospholipid antibodies; PTX: Pentraxin-3; Abs: antibodies; OD: optical density; IQR: interquartile range.ConclusionTo our knowledge, this is the first study which assessed the frequency of anti-PTX3 Abs in a cohort of SLE and/or APS pregnant women. These Abs occurred in the minority of patients (13.9%) and did not differ between SLE/APS women and controls. Due to our sample size, these findings need to be confirmed in larger cohorts.References[1]Cruciani L, et al. Journal of Perinatal Medicine, 2010:38.[2]Akolekar R, et al. Prenat. Diagn. 2009;29:934–8.[3]Bassi N, et al. Clinic Rev Allerg Immunol 2015;49:217–26.[4]Gatto M, et al. Journal of Autoimmunity, 2016;74:208–16.Disclosure of InterestsNone declared

BackgroundIt is well established that severe forms of SARS-CoV2 infection can induce a massive cytokine storm, which may disrupt the immune system stability and conceivably stimulate the development of reactive manifestations through a molecular mimicry process. Likewise, anti-COVID-19 vaccines, which have so far proved an excellent tolerability and safety profile, are able boost the immune response via different biologic technologies and adjuvant combinations possibly facilitating, in predisposed subjects, the onset of inflammatory or even autoimmune manifestations.ObjectivesWe report a case series of suspected rheumatic adverse events following immunization (AEFI) associated with anti-COVID-19 vaccine. We focused our attention on the prognosis of these patients by analysing their available follow-up data.MethodsWe included patients evaluated at first-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padua University Hospital between May and September 2021 presenting with new-onset rheumatic manifestation or a flare of an underlying rheumatic disease within 30 days after receiving an anti-COVID-19 vaccine dose. Inclusion and exclusion criteria were in accordance with the World Health Organization guidelines for AEFI surveillance. All patients were re-evaluated in January 2022: telemedicine or face-to-face visit. Response to therapy was classified as complete, good or absent according to the clinician’s judgment based on clinical examination, patient’s reporting and analysis of laboratory data.ResultsWe identified 30 cases of suspected rheumatic AEFI reported in Table 1. Comprehensively the most common manifestations were inflammatory arthritis (40.0%), rheumatic polymyalgia (26.7%) and adult-onset Still disease (13.3%). Among patients with an underlying rheumatic disease we recorded an AOSD flare, a rheumatoid arthritis flare with involvement of hands proximal interphalangeal joints, one case of wrist arthritis in a patient with psoriatic arthritis, one of aortitis in a patient with large vessels vasculitis, one case of polyarthritis in undifferentiated connective tissue disease and a nephritis flare in a patient with systemic lupus erythematosus.Treatment for the suspected AEFI was based on systemic glucocorticoids (GC) alone (63.3%), systemic GC plus IL-1R antagonists (13.3%), non-steroidal autoinflammatory drugs (13.3%), intra-articular GC (6.6%), colchicine (3.3%) and non-steroidal anti-inflammatory drugs (13.3%).At last follow-up contact (7.8±1.5 months) 26 patients (89.6%) were classified as complete responders. Eleven of them (42.3%) withdrew therapy without experiencing recurrence of disease manifestation. One patient with lupus nephritis had a proteinuric flare after the first BNT162b dose; he showed an initial good response to increased glucocorticoid therapy but had a new 24h proteinuria increase at second follow-up visit three months later requiring implementation of immunosuppressive therapy. Another patient with AOSD was in remission at last FU visit in December 2021 but required hospitalization in January 2022 for disease relapse due to a suspected gastrointestinal infection. Finally, one patient hospitalized for a seronegative polyarthritis after the first BNT162b dose achieved complete remission at last available contact (one month after hospital discharge) but was then lost in follow-up.ConclusionAfter a mean follow-up of 7.8±1.5 months nearly all of patients showed a complete/good response to standard therapy and about half of them withdrew the treatment without losing the remission statusReferencesDisclosure of Interests:None declared

BackgroundThere are uncertainties regarding the occurrence of idiopathic inflammatory myopathies (IIM) after infection by Severe Acute Respiratory Syndrome (SARS)-CoronaVirus2(CoV2) or in recipients of Coronavirus disease-19 (Covid-19) vaccines.ObjectivesHerein, the main objective was to assess temporal trends of newly diagnosed IIM in the past eight years, including the effects of the Covid-19 pandemic.MethodsWe extracted data of IIM patients from the Veneto Rare Disease Registry from 01/01/2014 and 31/12/2021. This regional registry has to be considered comprehensive of all patients with IIM in a specific geographical area. Hence, we extracted the following information: age; sex; date of diagnosis; type of IIM including dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASS), inclusion body myositis (IBM); place of residence. We restricted the analysis to IIM patients certified by expert rheumatologists belonging to the Regional Centre for Study and Treatment of Connective Tissue and other Rare Diseases at the Division of Rheumatology, University of Padua, Veneto, Italy. Finally, we compared new IIM cases before and after 04/01/2021 as the starting date for the vaccination campaign in Veneto. We reported descriptive statistics (median and interquartile range) and results of non-parametric tests to compare cases of IIM across the study period.ResultsDatabase extraction retrieved 192 people with IIM diagnosed during the study period (DM 85, PM 82, ASS 23, IBM 2; females 67.2%; median [25th-75th percentile] age at diagnosis 58.5 [49.6-68.5] years). There was a median of 2 [1-4] newly-diagnosed IIM monthly, with a non-significant increase in the post-pandemic two-year period 2020-2021 (Figure 1A). Numerically, 2020 had the most IIM diagnosis (N=30), mainly clustered in the second (N=12) and third (N=11) trimesters. Trends of new IIM diagnoses over one year course were similar during the study period, with visually identified higher IIM occurrence in February, April and September (Figure 1B). There was no difference in incident IIM cases in the 12 months before (N=31) and after (N=29) the initiation of the vaccination campaign (7 [5-9.8] vs 8 [3-12] new cases for each trimester; Mann-Whitney U test p=0.884). Finally, there was a significant trend for median age at diagnosis increasing by 6.46 years from 55.4 to 61.8 years between 2014 and 2021 (p=0.015, R2=0.344; repeated measures ANOVA with post test for linear trend).ConclusionWe found no significant change in patterns of IIM diagnoses between 2014 and 2021 besides a slight numerical increase in the second and third trimesters of 2020. In addition, we noted no signals of increased IIM diagnoses after introducing Covid-19 vaccines. This data encourage further analyses of larger, multicentre datasets from other geographical areas to clarify whether there has been variation in specific myositis subtypes across new-onset IIM after the pandemic.AcknowledgementsWe acknowledge Dr Monica Mazzuccato and Registro Malattie Rare - Regione Veneto for providing data.Disclosure of InterestsNone declared

Background:Treatment of systemic lupus erythematosus (SLE) is tailored according to the intensity of SLE disease activity and aims to achieve remission. Current definitions of remission and disease activity categories are mostly based on the SLE Disease Activity Index (SLEDAI), which has important limitations. The SLE Disease Activity Score (SLE-DAS) is a validated continuous disease activity score with higher accuracy in measuring SLE activity and higher sensitivity-to-change as compared to SLEDAI1. SLE-DAS is user-friendly with its online calculator.Objectives:To derive and validate the SLE-DAS cut-off values for defining SLE disease activity categories and SLE clinical remission state.Methods:Derivation study was conducted at the Padova Lupus Clinic. Validation was performed prospectively in patients from the Cochin Lupus Clinic and by post-hoc analysis of BLISS-76 (NCT00410384) trial. Gold-standard for clinical remission state was fulfillment of Definition Of Remission In SLE (DORIS). In Padova and Cochin Clinics, at time of inclusion, a senior clinician classified each patient as presenting: (i) remission, (ii) mild, or (iii) moderate/severe disease activity. Derivation of the SLE-DAS cut-offs for disease activity categories was performed using ROC curve analysis against this expert clinical classification. Performance of these SLE-DAS categories of disease activity was assessed as compared with: (i) expert classification (in Cochin cohort); (ii) British Isles Lupus Assessment Group (BILAG) index (in BLISS-76). An index-based and a Boolean definition of remission were tested applying decision trees, using CHAID (chi-square automatic interaction detection) algorithm and their performance estimated.Results:We included 1190 SLE patients (221 in Padova, 150 in Cochin and 819 from BLISS-76 cohorts). In the derivation cohort, best SLE-DAS cut-off values for disease activity categories were: (i) remission, SLE-DAS≤2.08; (ii) mild activity, 2.087.10. Table 1 shows the performance of these SLE-DAS cut-offs. The SLE-DAS Boolean-based definition of remission (all SLE-DAS clinical items scores = 0 and prednisone ≤5mg/day) showed sensitivity and specificity of 100% in the derivation (Padova) and validation (Cochin) clinical cohorts. The SLE-DAS index-based definition of remission (SLE-DAS ≤2.08 and prednisone ≤5mg/day) presented sensitivity =100% and specificity =97.4% in the derivation and validation clinical cohorts. The SLE-DAS definitions of remission were fully substantiated by CHAID.Table 1.Performance of SLE-DAS cut-offs for remission and disease activity categories compared to physician’s classification and BILAG (n =1190).Disease activity categorySensitivity (%)Specificity (%)Accuracy (%)DerivationPadova CohortRemission(SLE-DAS≤2.08)99.397.198.6Mild Disease Activity(2.0874.298.995.5Moderate and Severe Disease Activity(SLE-DAS>7.10)97.496.796.8ValidationCochin CohortRemission(SLE-DAS≤2.08)99.193.998.0Mild Disease Activity(2.0882.699.296.7Moderate and Severe Disease Activity(SLE-DAS>7.10)100.098.698.7ValidationBLISS-76Remission and Mild Disease Activity§vs. Moderate and Severe Disease Activity§§ (SLE-DAS≤7.10 vs. >7.10)91.484.190.8§ Remission/Mild: No BILAG B or A scores§§ Moderate/severe: ≥1 BILAG B or A scoresConclusion:The SLE-DAS is an accurate and easy to use tool for defining clinical remission state and SLE disease activity categories, validated with both the expert assessment and BILAG.References:[1]Jesus D, et al. Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity. Ann Rheum Dis 2019;78:365-71.Acknowledgements:The authors would like to thank GlaxoSmithKline (Uxbridge, UK) for granting access to the data from the BLISS-76 trial through the Clinical Study Data Request consortium.Disclosure of Interests:None declared

Background:anti-NXP2 antibodies is considered a serological marker of dermatomyositis (DM), with calcinosis, severe myositis and, in some series, cancer. Historically, these associations have been detected with immunoprecipitation (IP), but in the last few years commercial lineblot (LB) assay have been released.Objectives:to analyze the clinical features associated to anti-NXP2 antibodies, including the onset of concomitant cancers, both with LB and homemade IPMethods:clinical and serological data from medical charts of 213 patients with a diagnosis of inflammatory miosidites without anti-NXP2 (NXP2-), followed-up by two third-level Centers, and 61 anti-NXP2+ patients from 10 Rheumatological centers were analyzed. Anti-myositis specific (MSA) and anti-myositis associated antibodies (MAA) were detected in single centers by LB (Euroimmun Autoimmune Inflammatory Myopathies 16 antigens). Anti-NXP2 was confirmed by protein and RNA IP, as previously described (1)Results:clinical diagnosis of anti-NXP2+ positive with LB were 42 DM, 11 PM, inclusion body myositis (IBM) 4, necrotizing myositis and overlap (OM) 1 each. Anti-NXP2+ showed a lower age at onset (pIP did not confirmed anti-NXP2 antibodies in 18 sera: in 4 cases at least one MSA/MAA was identified by IP; these 18 patients did not show differences when compared with 213 anti-NXP2-.Conclusion:Protein IP confirmed anti-NXP2 antibodies in 63% of LB+ sera. Double positive cases showed more typical DM features and rarely occurred in IIM not DM. Anti-NXP2 positivity by LB should be confirmed by other methods in order to correctly diagnose and characterize IIM patients.References:[1]Arthritis Res Ther 2012,30;14:R97Acknowledgments:Forum Italiano per la Ricerca Malattie Autoimmuni (FIRMA)Disclosure of Interests:Micaela Fredi: None declared, Ilaria Cavazzana: None declared, Angela Ceribelli: None declared, Maria Grazia Lazzaroni: None declared, Simone Barsotti: None declared, Maurizio Benucci: None declared, Lorenzo Cavagna: None declared, Ludovico De Stefano: None declared, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Giacomo Emmi: None declared, Marco Fornaro: None declared, Federica Furini: None declared, Roberto Gerli: None declared, Maria Grazia Giudizi: None declared, Marcello Govoni: None declared, Anna Ghirardello: None declared, Luca Iaccarino Speakers bureau: GSK, Pfizer, Janssen, Novartis, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Maria Infantino: None declared, Alessandro Mathieu: None declared, Emiliano Marasco: None declared, Paola Migliorini: None declared, Boaz Palterer: None declared, paola parronchi: None declared, Matteo Piga: None declared, Federico Pratesi: None declared, Antonella Radice: None declared, Carlo Selmi: None declared, Valeria Riccieri: None declared, Marilin Tampoia: None declared, Giovanni Zanframundo: None declared, Angela Tincani: None declared, Franco Franceschini: None declared

We analytically analyze radial expansion/contraction of a hollow sphere composed of a second-order elastic, isotropic, incompressible and inhomogeneous material to delineate differences and similarities between solutions of the first- and the second-order problems. The two elastic moduli are assumed to be either affine or power-law functions of the radial coordinate R in the undeformed reference configuration. For the affine variation of the shear modulus μ, the hoop stress for the linear elastic (or the first-order) problem at the point R=(RouRin(Rou+Rin)/2)1/3 is independent of the slope of the μ vs. R line. Here Rin and Rou equal, respectively, the inner and the outer radius of the sphere in the reference configuration. For μ(R)∝Rn, for the linear problem, the hoop stress is constant in the sphere for n=1. However, no such results are found for the second-order (i.e., materially nonlinear) problem. Whereas for the first-order problem the shear modulus influences only the radial displacement and not the stresses, for the second-order problem the two elastic constants affect both the radial displacement and the stresses. In a very thick homogeneous hollow sphere subjected only to pressure on the outer surface, the hoop stress at a point on the inner surface depends upon values of the two elastic moduli. Thus conclusions drawn from the analysis of the first-order problem do not hold for the second-order problem. Closed form solutions for the displacement and stresses for the first-order and the second-order problems provided herein can be used to verify solutions of the problem obtained by using numerical methods.

Autoimmune rheumatic diseases (ARD) affect young females durrng childearing age. Over the last decades, improvements in survival as well as quality of life in patients affected with ARD have led to an increased number of pregnancies observed during the course of such diseases. Systemic lupus erythematosus (SLE) is the most frequently observed ARD during pregnancy, and the immunoendocrine changes occurring during pregnancy may influence the course of this disease. Pregnancy can also occur in patients with rare ARD, namely systemic sclerosis, polymyositis/dermatomyositis, systemic vasculitis including Wegener's granulomatosis, Churg-Strauss syndrome, polyarteritis nodosa, microscopic polyangiitis, Takayasu arteritis and Behcet disease. This review focuses on the complications during pregnancy caused by these rare ARD, and we briefly discuss the data published on these disorders. Some guidelines for the management of these conditions during pregnancy will also be provided. However, it is important to note that data on pregnancy outcome are very limited and, in the absence of prospective studies, most of the information derives from case reports and retrospective studies.

Objective: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE). Methods: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-s2-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed. Results: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT. Conclusions: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.

In this paper we deal with Signorini’s method for live loads to derive approximate solutions of some pure traction boundary value problems in finite elastostatics. Then, the obtained solutions are used to determine the second-order constitutive constants of a homogeneous and isotropic elastic material.

Mycophenolate mofetil (MMF) is an immunosuppressive agent initially used in the treatment of transplant recipients. MMF has been used in renal, heart, and liver transplantation, where it seems more effective than other immunosuppressive regimens in reducing the incidence of acute rejection episodes. MMF has a variety of immunosuppressive effects, including selective suppression of T and B lymphocyte proliferation, and has been more recently used in many autoimmune inflammatory conditions. Systemic lupus erythematosus (SLE) is an autoimmune disease that can potentially involve any organ or system of the human body. Glomerulonephritis (GLN) has been recognized as the most frequent severe manifestation of SLE, leading to poor long-term prognosis. In the treatment of lupus GLN, several therapeutic approaches, all including immunosuppressive drugs, such as cyclophosphamide, azathioprine, or cyclosporine A, have been used. The short- and long-term toxicity of these drugs limits their use in a substantial number of patients. Over the last few years, MMF has emerged as an alternative therapeutic regimen in lupus GLN, mainly for patients refractory to other therapies. These studies have shown that it is highly effective and generally well tolerated.

Autoimmune rheumatic diseases (ARD) affect young females during childbearing age. Over the last decades, improvements in survival as well as quality of life in patients affected with ARD have led to an increased number of pregnancies observed during the course of such diseases. Systemic lupus erythematosus (SLE) is the most frequently observed ARD during pregnancy, and the immunoendocrine changes occurring during pregnancy may influence the course of this disease. Pregnancy can also occur in patients with rare ARD, namely systemic sclerosis, polymyositis/dermatomyositis, systemic vasculitis including Wegener's granulomatosis, Churg-Strauss syndrome, polyarteritis nodosa, microscopic polyangiitis, Takayasu arteritis and Behçet disease. This review focuses on the complications during pregnancy caused by these rare ARD, and we briefly discuss the data published on these disorders. Some guidelines for the management of these conditions during pregnancy will also be provided. However, it is important to note that data on pregnancy outcome are very limited and, in the absence of prospective studies, most of the information derives from case reports and retrospective studies.

Antiphospholipid antibody syndrome is characterized by venous and/or arterial thrombosis and/or pregnancy morbidity associated with antiphospholipid antibodies (aPL), such as anticardiolipin antibodies, anti beta 2 glycoprotein I antibodies and positive lupus anticoagulant test. This syndrome may potentially affects any organ system including the skin. Livedo reticularis is the most frequently observed cutaneous lesion; other lesions, by order of frequency, are ulcerations, digital gangrene, subungueal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis and primary anetoderma. Skin lesions are more frequently observed in the catastrophic antiphospholipid syndrome, characterized by widespread microvascular occlusions involving multiple organs simultaneously. Patients with antiphospholipid associated thrombosis should receive long-term oral anticoagulants. The intensity of anticoagulation should be guided according to the nature of the thrombotic event (venous vs. arterial thrombosis). Patients with aPL-associated pregnancy morbidity should be treated with aspirin plus heparin and closely monitored during pregnancy. The treatment of the catastrophic antiphospholipid syndrome remains unsatisfactory. High dose intravenous steroids and parenteral anticoagulation should be supplemented by intravenous gammaglobulin and repeated plasma exchanges using fresh frozen plasma early on in the course of the syndrome.

Cutaneous manifestations of patients with lupus erythematosus (LE) are very frequent, show a great variety and can occur at any stage of the disease. The most consistent environmental trigger factors so far recognized are exposure to ultraviolet light and certain drug classes known to be capable of inducing LE in otherwise healthy individuals. A classification system has been established including clinical, histologic, photobiologic, serologic, and immunogenetic findings to better define the different cutaneous subtypes of LE. During their clinical evolution, the cutaneous manifestations vary considerably, and, therefore, the diseases which should be considered in differential diagnosis are different, according to the stages of disease development. Furthermore, 25 years of experience worldwide have revealed that individuals whose disease presentation is dominated by subacute cutaneous LE skin lesions and the presence of circulating anti-Ro/SS-A antibodies represent a rather homogeneous immunogenetic subphenotype of LE that enjoys a good prognosis over time. Treatment should be individualized according to disease severity. The majority of patients with cutaneous manifestations of LE do not require systemic immuno-suppressive/ immunomodulatory therapy and the advent of recombinant biologicals has given hope to the small percentage of patients that suffer from particularly severe skin disease activity.

Objective To investigate the role of clinical, immunological and psychological variables in influencing the health-related quality of life (HRQOL) of Italian patients with systemic lupus erythematosus (SLE). Methods The Medical Outcomes Study Short Form-36 was applied in a cohort of 126 SLE patients. At the time of HRQOL testing all patients underwent a clinical and laboratory evaluation, together with the measure of disease activity, severity and damage. In addition, a battery of psychological tests including the Hamilton Anxiety Scale (HAS) and the Hamilton Depression Rating scale (HAM-D) was applied. Results The parameters which seemed to greatly influence the impairment of HRQOL were older age, arthralgia-arthritis and higher HAS scores as well as HAM-D. In multivariate analysis (adjusted for age), arthralgia-arthritis and a higher HAM-D score were associated with HRQOL impairment. No relationship between HRQOL and SLE activity, severity or damage were found. However, a relationship between HAS or HAM-D scores and damage or arthralgia-arthritis was noted. Conclusion Anxiety, depression and joint pain seem to be the major determinants of HRQOL impairment in SLE patients. Damage seems to influence HRQOL mostly through depression.

Objective. To examine health-related quality of life (HRQOL) in Italian patients with systemic lupus erythematosus (SLE) and compare it with that of healthy people, and to investigate relationships among different dimensions and subscales of a generic health status measure. Methods. The Medical Outcomes Study Short Form-36 (SF-36) was applied in a cohort of 126 consecutive SLE patients and 96 healthy controls. At the time of HRQOL testing, all patients underwent clinical and laboratory evaluation. Results. Both physical (PCS) and mental (MCS) component summary scores of the SF-36 were reduced in patients compared with controls. In SLE great variability in all the subscales was observed. Significant correlations between PCS and MCS and between many different subscales were observed in patients but not in controls. The PCS was higher than MCS more frequently in controls than in SLE patients (81 vs 48.4%, P

Objective: To investigate the reliability of the immunoblot method in the detection of serum immunoreactivity towards the B/B’ polypeptides of U small nuclear ribonucleoproteins (UsnRNP) and to assess the significance of these antibodies in connective tissue disease (CTD) patients. Methods: We tested the sera of 348 patients with CTD (101 SLE, 51 systemic sclerosis, 53 primary Sjogren’s syndrome, 27 poly/dermatomyositis, 15 rheumatoid arthritis and 101 overlap CTD), of 31 matched healthy subjects and 13 patients with primary Epstein-Barr virus (EBV) infection with high titre IgG anti-EBV antibodies. IgG anti-UsnRNP antibodies were determined by immunoblotting on nuclear extract from Raji cells (an EBV-immortalised human B lymphoid cell line) and Jurkat cells (a human T lymphoid cell line). Anti-dsDNA antibodies were detected by indirect immunofluorescence on Crithidia luciliae and anti-ENA by counterimmunoelectrophoresis. Anti-dsDNA activity and avidity were measured in SLE sera by ELISA with Scatchard analysis. Results were statistically analysed by chi-square and Mann-Whitney tests. Results: A high frequency of anti-B/B’ antibodies was found in the sera of CTD patients, confined to SLE (54.4%) and overlap CTD with SLE features (55,2%). Anti-B/B’ immune reactivity was closely associated with other anti-UsnRNP specificities, gel precipitating anti-nRNP and anti-P antibodies. Nine out of 15 (60%) anti-B/B’ positive/anti-ENA negative lupus sera on Raji blots were confirmed to be positive also on Jurkat blots. The sera from patients with EBV infection provided, on Raji blots, completely different band patterns from those obtained with auto-immune sera. Conclusions. The Sm B/B’ proteins are the predominant or, at least, the most frequently targeted antigens of the UsnRNP auto-immune response in SLE and “lupus-like” overlap CTD. Moreover, anti-B/B’ is diagnostically specific for CTD with SLE features. Immunoblotting on human B lymphoid cells is a reliable method, in terms of sensitivity and specificity, for the detection of anti-Sm B/B’ antibodies.

Two hundred and sixty-three patients consecutively admitted to our Unit for CLD were investigated for the antibody to Hepatitis C Virus (anti-HCV) in the serum using the recently developed enzyme immunoassay. The overall prevalence of anti-HCV was 45%; in patients with cryptogenic CLD it was significantly higher (69%) than in patients with markers of viral hepatitis (15%). Anti-HCV was found in 62% of the patients with hepatocellular carcinoma; this finding favours a potential role of HCV in determining the neoplastic transformation of the cirrhotic liver. In alcoholic liver disease the prevalence of anti-HCV was 52%; this finding poses the interesting question of aethiology of liver damage in these patients. The presence of anti-HCV was significantly associated with older age, irrespective of aethiology and stage of liver disease. The importance of the detection of this antibody for the aethiological diagnosis of chronic liver damage remains to be elucidated.

The prevalence of hepatitis B virus (HBV) serological markers was determined in a prospective fashion by radioimmunoassay in 2,084 healthy volunteer blood donors. The results showed that 51.2% of the donors were positive for at least one marker, and the percentage of occurrence of each marker was: HBsAg 5.3, anti-HBs alone 1.7, anti-HBc alone 10.8, anti-HBs and anti-HBc 33.3. Because of the size of the problem this investigation strongly demands further studies on the potential role of blood positive for anti-HBc in transmitting HBV infection in our geographical area.

Mechanical and calorimetric analyses have been carried out on four glass fibre laminated polyester resins (isophthalic, vinyl ester and bisphenol A and B) aged in liquid water at 20°C and 90°C, and the water uptake kinetics are described. Weight losses, disc shaped crack formation, embrittlement, fibre debonding and delamination are the principal morphological changes observed. The autocatalytic hydrolysis of the ester groups may be responsible for the chemical degradation. The hydrolytic stability of the systems investigated was improved by the inclusion of fewer ester groups in the repeating units of the initial polyester prepolymer.

The test procedures and equipment, specified in ASTM Stnadard D2992 for determining the long-term performance of GRP pipes under pressure, are described. The limitations and problems involved with the D2992 test are discussed, and a new method aimed at overcoming these problems is described. Preliminary results obtained with the new test procedure are presented.

A mechanical and calorimetric analysis was performed on a glass fibre-reinforced polyester resin aged in water at different temperatures. Data were compared for the dry and aged matrix and composites. The exposure of the resin and composite to water at different temperatures induced modifications in the mechanical properties and the morphology of the polymeric samples. The loss of low molecular weight components initially present in the resin, plays an important role in the embrittlement of the samples.

Successful processing of unsaturated polyester resins requires a knowledge of the relationships between the rheological behaviour and the cure kinetics of the reacting material. The heat generated by the exothermic reactions during the cure alters the optimum isothermal condition with a resultant increase in temperature in large parts: this can give rise to the formation of non-homogeneous material. Mechanical and calorimetric (DSC) analyses have been performed on glass fibre laminates, using two different bisphenolic polyester as matrices, aged in water at 20°C and 90°C. The critical kinetic and geometric parameters required to avoid uncontrolled unsteady state reaction conditions are described.