Background: Systemic sclerosis (SSc) is characterized by progressive fibrosis and microvascular dysfunction that involves multiple organ systems, including kidneys. Kidney involvement, beyond the scleroderma renal crisis (SRC), is often asymptomatic and underdiagnosed, associated with subclinical renal vasculopathy characterized by abnormalities in renal microcirculation and mild changes of glomerular filtration rate (GFR). Kidney involvement is rare in isolated Sjögren's syndrome (SS) and reported between 5% and 14% in european patients and approximately 30% in asian patients. Objectives: The aim of the study was to assess renal involvement in SSc and SS and follow its progression over a three-year period. Methods: Patients with SSc (2013 EULAR criteria) and isolated SS (2016 ACR/EULAR criteria) were consecutively enrolled. Demographic and clinical characteristics at baseline (T0) were gathered including sex, age, body mass index (BMI), history of essential hypertension and diabetes, serum creatinine, and estimated GFR calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Exclusion criteria were presence of SRC, atherosclerosis renal artery stenosis and other secondary causes of hypertension, glomerulonephritis, urinary tract obstruction, urinary infections, heart failure, pulmonary arterial hypertension, malignancies. All patients were followed for three years (T1) with renal function assessment. Group comparisons were made using the Student's t-test or Mann-Whitney test for continuous variables and the chi-square test or Fisher's exact test for categorical variables. A significance level of p<0.05 was considered. Results: A total of 248 patients were enrolled, 127 SSc and 121 SS patients. Their features at baseline (T0) are summarized in Table 1. Table 2 summarizes the comparative analysis of renal function between SSc and SS patients at baseline and after 3 years. SS patients had similar median serum creatinine both at T0 and at T1 [0.78 mg/dl (IQR 0.68;0.84) vs 0.78 mg/dl (IQR 0.7;0.84), p>0.05], but a higher eGFR at T0 than at T1 [87.9 ml/min (IQR 72.6;102.3) vs 86.4 ml/min (IQR 72.7;96.7), p<0.05], with a variation of −2.1 ml/min (IQR −11.4;1.1). SSc patients had a statistically significant lower median serum creatinine at T0 than at T1 [0.7 mg/dl (IQR 0.6;0.8) vs 0.8 mg/dl (IQR 0.7;0.9), p<0.001], with a variation of 0.1 mg/dl (IQR 0;0.2), and a statistically significant higher median eGFR at T0 than at T1 [97 ml/min (IQR 85;108.5) vs 91 ml/min (IQR 73;103), p<0.001], with a variation of −3 ml/min (IQR −18;−1). In both SSc and SS eGFR median variation was statistically significant higher in patients affected by systemic arterial hypertension compared to those without [−12.2 ml/min (IQR −16.32;5.42) vs −1.8 ml/min (IQR −3;0.4), p<0.01 for SS patients and −18 ml/min (IQR −26; −12) vs −2 ml/min (IQR −7;2.25), p<0.001 for SSc].SSc patients had a significantly higher variation compared to SS patients both for median serum creatinine [0.1 mg/dl (IQR 0;0.2) vs 0 mg/dl (IQR −0.1;0.1), p<0.05] and median eGFR [−3 ml/min (IQR −18;−1) vs −2.1 ml/min (IQR −11.4;1.1), p<0.05]. Conclusion: In both SSc and SS patients, renal involvement exhibited a subclinical pattern (eGFR > 60 ml/min). This preliminary study also highlights slight differences in renal involvement and its progression between the two groups considered. In SSc patients, creatinine levels at T0 are, on average, lower than in pSS patients possibly linked to their reduced muscle mass. Over time, SSc patients tend to show a tendency toward eGFR reduction, for the continuous microvascular damage leading to chronic hypoxic-ischemic injury. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: To fulfil the energy demands upon activation, lymphocytes undergo a profound metabolic reprogramming (i.e switch towards glycolysis), which sustains their pro-inflammatory function. This concept, which is known under the term “immune-metabolism” [1], has become of great interest in rheumatic diseases; however, little is known in Sjogren Disease (SD). As infiltrating T and B cells forming aggregates (named foci) are the hallmark of SD and display a major pathogenic role, investigating the contribute of metabolic reprogramming, especially glycolysis, in these cells looks particularly relevant. Objectives: Aim of this study is to evaluate the expression of the glucose transporter marker GLUT-1 in lymphocytes infiltrating SD minor SG and to assess its correlation with the severity of inflammatory infiltrates. Methods: The expression of GLUT-1 on CD3+ and CD20+ lymphocytes infiltrating minor SG from patients with SD, has been evaluated by IFI in 9 different biopsies samples. Biopsies were divided in three groups according to composition and the level of organization of the foci:-G1: small foci mainly composed by CD3+ cells (Small) (n=3)-G2: large foci segregated in CD3+ and CD20+ areas [Segregated Foci (SF)] (n=3)-G3: large SF with CD21+ staining indicative of Germinal Center like structures (GC) (n=3)The quantification of the expression of GLUT-1 on lymphocytes was performed by digital imaging analysis (DIA) with QuPath software. GLUT-1 expression was quantified overall and selectively on CD3+ or CD20+ lymphocytes. To visualize SG areas with the highest expression of GLUT-1, density-maps were generated. Analysis of variance (ANOVA) and pairwise comparisons (Bonferroni correction) were performed to evaluate differences in the expression of GLUT-1 both according to the grading of inflammation (G1-G2-G3) and according to the type of foci (Small-SF-GC). Results: Across the three groups (G1-G2-G3), a remarkably different GLUT-1 expression on infiltrating lymphocytes was detected (Figure 1a). Despite the evident increase from G1 to both G2 and G3, statistical significance was not achieved in pairwise comparisons [G1 (9,6%±3,8) vs G2 (37,7%±13,7), p=0.069; G2 vs G3 (34,1%±3,7), p=1]. The selective analysis for CD3+ and CD20+ cells showed similar results. Compared to G3, in G1 and G2 CD20+ cells showed a slightly lower rate of GLUT-1 (Figure 1a). Across the three types of foci, GLUT-1 expression on lymphocytes also significantly differed (Figure 1b). In pairwise comparison a significant difference between Small (13,7%±11,8) and SF (31,7%±17,9)(p=0.008) was detected while significancy was not reached in Small vs GC (26,8%±11,7)(p=0.338) and SF vs GC (p=1) (Figure 1b). Similar results were obtained when CD3+ and CD20+ cells were analysed separately (Figure 1b). Representative images of GLUT-1 density-maps in the G3 group and GLUT-1 expression in the different types of infiltrates are reported in Figure 1c-d. Conclusion: This is the first study identifying the expression of the glycolysis marker GLUT-1 on both T and B lymphocytes infiltrating SD SG. An increase in GLUT-1+ lymphocytes was detected according to the severity of inflammation and reached the highest levels in large, organized foci. Despite preliminary, our findings suggest that activation of glucose metabolism may be associated with tissue lymphocytes activation and proliferation. Validation studies on a larger sample size are ongoing to confirm these findings and further investigate the role of glycolysis in SD infiltrating lymphocytes. REFERENCES: [1] O’Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016 Sep;16(9):553-65 Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1

Background: In patients with Sjögren's Syndrome (SS), the biopsy of minor salivary glands (MSG) is a fundamental diagnostic and prognostic tool. However, there is still variability in the histological parameters considered, and the clinical/laboratory associations are yet to be clarified. Objectives: Aim of this study is to investigate in a large monocentric cohort of primary SS patients (Sjogren Clinic at University of Rome Sapienza), the predictive value of MSG histology versus the main clinical, clinimetric and laboratory features. Methods: Primary SS patients undergoing MSG biopsy between 2016 and 2023 were retrospectively enrolled and the histological/clinical/clinimetric/laboratory data were collected. Histological analysis comprised: focus score (FS) and n° of foci calculation, germinal centers (GCs) [nodular aggregates (H&E), confirmed by CD21+ or Bcl6+ (IHC)] and lymphoepithelial lesions (LEL) (CD20+ IHC in ducts) detection and fibrosis (H&E) recognition. Logistic and linear regression analyses were performed to evaluate the predictive value of histology on clinical/clinimetric/laboratory parameters. Results: Two-hundred and thirty-two SS patients were enrolled [mean age 53.6 years (±13.6), F=223/M=9] (figure 1). Both the FS and the n° of foci were predictive of anti-La/SSB, RF, hypergammaglobulinemia and were positively correlated with the ESSDAI. Wile the FS was predictive for low C4 levels, the n° of foci was predictive for anti-Ro/SSA, monoclonal component, biologic and glandular ESSDAI domains. As we recently published [1], a lower FS and n° of foci was predictive for the presence of autoimmune thyroiditis. We found a large agreement between CD21+ and Bcl6+ staining. The presence of GCs (either CD21+ or Bcl6+) was predictive for those serological features associated with a more severe disease. GCs were also predictive of specific ESSDAI domains linked with higher risk of lymphoproliferative complications (Figure 1). Both the CD21+ and the Bcl6+ stainings were predictive of an higher ESSDAI score. Compared to GCs, LEL were even more predictive of different serological features and ESSDAI domains (Figure 1). Interestingly, the presence of fibrosis was associated with a lack of anti-Ro/SSA-La/SSB antibodies. Three patients developed MALT lymphoma; all of them had GCs (CD21+/Bcl6+) and LEL in their MSG biopsies, none had fibrosis [n° of foci: mean=8.3 (SD:5-13); FS mean=3.6 (SD=2.12-4.88)]. Conclusion: This is one of the largest studies evaluating the predictive value of histology versus different clinical, clinimetric and laboratory parameters of patients with primary SS. Our data confirm the association between a higher FS and the presence of both serological features known to be linked to a more severe disease and higher ESSDAI score values. Compared to the FS, the number of foci revealed additional associations such as the biological and glandular ESSDAI domains. We confirm the association between GCs and those serological/clinical features accompanying a more systemic and active disease and we provide evidence of the same, and also additional associations, for the LEL. Finally, we demonstrate for the first time that the presence of fibrosis may be predictive of seronegative patients; this relevant finding, is currently under validation on a larger cohort. REFERENCES: [1] Colafrancesco S, et al. Clinical and histological features of patients with primary Sjögren's syndrome and autoimmune thyroiditis: a national multicentre cross-sectional study. Clin Exp Rheumatol. 2023;41(12):2389-2396. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: In Sjögren Disease (SD) salivary gland epithelial cells (SGEC) sustain inflammation due to their acquired capacity to express/secrete adhesion/pro-inflammatory molecules. However, the mechanisms responsible for SGECs activation remain undetermined. The link between immune cells’ function and cells’ metabolic reprogramming is known under the term “immunometabolism” and has become one of the most exciting areas of investigation in the field of immuno-rheumatology, despite its relevance in SD has not been investigated as yet.We hypothesize that the altered cell energy metabolism of SGECs is a central driver of SG inflammation in SD and one that is targetable for the development of innovative therapies. Objectives: I–To determine (in vivo) in a viral-induced model of experimental sialoadenitis the relationship between SG inflammation and cell metabolic reprogramming;II–To identify ex vivo the main metabolic pathways differing between SD and sicca (control) SGECs;III–To assess ex vivo and in vitro the expression of glycolysis in SGECs and to investigate its contribution to SGECs activation. Methods: Aim I- SD mouse models were produced. After culling at different time points [day_0 (non-cannulated), day_5-12-19 (cannulated)], SG bulk RNA-seq analysis focused on metabolic pathways was conducted. Aim II- The metabolic profile of cultured SGECs from SD and sicca patients was analysed (mass spectrometry). Aim III- The expression of the glycolysis marker GLUT-1, along with lymphocytes (CD45+) and epithelial cells (PanCK+, CK7+, CK14+) markers, was determined (IFI) on paraffin-embedded sections of SD and sicca minor SG. SGECs cultures were treated as follows: 1) fluorescent glucose (6-NBDG), to assess glucose up-take; 2) 2-deoxy-glucose (2DG), to evaluate the effect of glycolysis inhibition on SGECs activation [ICAM-1 expression (IFI) and IL-6/type-I IFN production (Elisa and IFNα/β reporter cells)]; treatment conditions are in Figure 1d. Results: Aim-I: Following the inflammatory insult, bulk RNA-seq analysis in AdV-induced sialoadenitis, demonstrated changes in the SG metabolic profile. Down-regulation of specific pathways (i.e. oxidative phosphorylation and pyruvate metabolism), occurred up to day 12 post-cannulation (Figure 1a).Aim-II: A metabolic difference between SGECs from SD and sicca patients was revealed (i.e. glycolysis and TCA cycles) (Figure 1b).Aim III: As glycolysis turned out to be one of the most expressed pathways in SD, we further investigated its expression in SGECs. The expression of the glucose transporter GLUT-1 was highly detected in SD SG tissue by SGECs wile no expression was detected in sicca. Such GLUT-1 expression was mainly localized in ducts, especialy in ductal luminal cytokeratin-7 positive (CK7+) cells (Figure 1c). In vitro treatment of SGECs with fluorescent glucose demonstrated an higher glucose uptake in SD SGECs (representative example-Figure 1c). In primary SGECs culture, following stimulation with Poly(I:C), which mimics viral sensing by SGEC, an increase in IL-6, type-I IFN and the adhesion molecule ICAM-1 was observed. SGECs treatment with the glycolisis-inhibitor 2DG prevented [if Poly(I:C) and 2DG were administered concomitantly] or reduced [if 2DG was added following 12h stimulation with Poly(I:C)] the expression of adhesion/pro-inflammatory molecules (Figure 1d). Conclusion: In vivo experiments confirm that inflammation is intimately linked with metabolic changes occurring in SD SG. After induction of inflammation, we observed a down-regulation of oxidative phosphorylation and changes in glucose metabolism. Mass spectometry analysis confirmed the higher expression of specific metabolic pathways in SD SGECs, such as glycolysis. The increased expression of GLUT-1 in SD CK7+ ductal epithelial cells and the higher glucose up-take in SD cultured SGECs confirm such a shift towards glycolysis. Remarkably, glycolysis inhibition affects SGECs activation, indicating that metabolic reprogramming is likely responsible for their pathogenic behaviour. In vivo investigations on the potential utility of drugs targeting glycolysis in SD are currently ongoing. REFERENCES: NIL. Acknowledgements: The presenting author of this abstract (SC) is recipient of a “Career Research Grant” funded by FOREUM – Foundation for Research in Rheumatology. Disclosure of Interests: None declared.Figure 1

Background: Sjögren syndrome (SS) is an autoimmune disorder characterized by chronic inflammation of exocrine glands and histological features of focal lymphocytic sialoadenitis. While the innate immune mechanisms display a major role at early stages of the disease, the adaptive immune system is the main driver of inflammation at later phases. Although the innate immune pathway of IL-1 displays great pro-inflammatory effect in different inflammatory conditions, its role in SS is still poorly defined. The so called ”activation” of salivary gland epithelial cells (SGECs) is key in the pathogenesis of SS and we recently described how this process is intrinsically linked to the activation of autophagy. The mechanisms behind SGECs activation remain unclear as well as their relationship with innate immune pathways and, in particular, with the IL-1 pathway. The few available data suggest that the expression of IL-1β is upregulated in activated epithelial cells from SS lacrimal glands; accordingly, increased assembly of the inflammasome complex NLRP3 has been described in the SG of SS mice models. Little is known about the role of the other isoform of IL-1 named IL-1α, an “alarmin” passively released by cells following damage with interesting effects in different rheumatic conditions. Objectives: Aim of this study is to investigate the IL-1 pathway, with particular regard to the expression of the two isoforms of IL-1 (α and β), in SS salivary glands and to assess its role in SGECs activation and homeostasis. Methods: The study was divided in two parts, a descriptive and a functional one. Descriptive study – Paraffin embedded minor SG biopsies (MSG) were collected from patients with SS and sicca syndrome (controls). Immunofluorescence staining for IL-1α and IL-1β detection were performed along with markers to localize their expression; these markers included SGECs markers (panCK, CK7, CK14) and lymphocytes markers (CD45, CD3, CD20). Functional study – SGECs cultures from SS and sicca MSG were produced. Supernatants were analysed by ELISA for the detection of IL-1 family cytokines. On a human SG cell line (HSG), in vitro treatments with activating stimuli [Poly(I:C) and LPS] and then with IL-1 inhibitors (Anakinra, blocking both IL-1α and IL-1β; Canakinumab, selectively binding IL-1β) were performed. Following treatments, changes in the expression of autophagy (LC3IIB and p62), apoptosis (annexin V) and activation (ICAM-1) markers were assessed by Western Blot and flow cytometry. Results: Descriptive study - IL-1α expression was detected both in MSG sections from patients with SS and in MSG from patients with sicca; its expression was mainly localized in luminal CK7 positive ductal epithelial cells. No expression was detected in acinar cells and infiltrates. The expression of IL-1β was not detectable neither in infiltrates nor in SGECs (Figure 1a). Functional study - Analyses of supernatants from SGECs cultures revealed slightly higher levels of IL-1α and IL-1β in SS compared to sicca, however the difference was not statistically significant (Figure 1b). Following HSG stimulation with Poly(I:C) and LPS, an increase in autophagy (increased LC3IIB, decreased p62) and activation (ICAM-1), and a slight increase in apoptosis (annexin V), were observed. Both treatments with Anakinra and Canakinumab induced a reduction in autophagy and a slight downregulation of activation markers; only anakinra determined a decrease in apoptosis while canakinumab displayed opposite effects (Figure 1c, d). Conclusion: The lack of expression of IL1β at tissue level might suggest that this pathway is mainly involved in the early phases of the disease rather than during the course of an established disease. Despite the absence of specificity for SS, the expression of IL1α at ductal epithelial cell level is quite interesting and worth of further investigation. In addition, the indirect evidence of an alteration in homeostasis and activation of SGECs following inhibition of IL-1 pathways, might suggest a role of this molecule in two of the major pathogenic mechanisms driving the development of an autoimmune epithelitis. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1

Background Salivary glands epithelial cells (SGECs) activation and loss of homeostasis play a key role in primary Sjogren Syndrome (pSS) [1]. High serum and saliva levels of β2-mycroglobulin (β2-M) have been described [2] in pSS, however, the exact origin of this molecule is still unclear. Our preliminary data from single cell analysis on pSS salivary glands treated with immunosuppressors show a downregulation of this protein in SGECs following treatment. Objectives Aim of this study is to evaluate the expression of β2-M in pSS SGECs and to dissect its modulation in inflammatory conditions. Methods To mimic the inflammatory microenvironment of pSS, a human salivary gland (HSG) cell line was treated (48h) with 1) Poly-I:C (40 μg/ml), 2) LPS (50 μg/ml), 3) culture medium (untreated). The HSG expression of β2-M (Ab anti-β2-M) was evaluated by flow cytometry along with the expression of apoptotic [(annexin V (MBL)] and activation [ICAM-1 (Ab anti-CD54)] molecules. Ex vivo expression of β2-M was then assessed in SGECs deriving from both pSS patients (n=3) and sicca (controls) (n=3). Results In the HSG cell line treated with both Poly I:C and LPS a significant increase in β2-M was documented [mean fluorescence index (MFI): untreated=1 (1-1), Poly-I:C=2.46 (1.5-3.9), LPS=1.3 (1-1.3); p=0.003]. The increased expression of β2-M was paralleled by an increase in ICAM-1 (MFI: untreated=1 (1-1), Poly-I:C=1.61 (1-2.5), LPS=1.26 (1-1.2); p=0.06) and annexin V (mean%: untreated=7.6% (5-9), Poly-I:C=14.3% (9-18), LPS=8% (6-11); p=0.003). In SGECs from pSS a higher expression of β2-M was detected as compared to controls (MFI: pSS=2.5 (2-3) vs sicca=1 (0.5–1.5) (Figure 1). Conclusion Our preliminary data suggest that β2-M is actively expressed by SGECs in pSS and that its exposure is driven by the local inflammatory milieu. Such expression is particularly interesting in view of the already demonstrated capacity of β2-M to activate pro-inflammatory pathways and to influence cellular viability and autoantigens exposure [3]. Functional studies are currently ongoing to dissect the potential pathogenic role of β2-M in pSS. References [1] Colafrancesco S, et al. Arthritis Rheumatol. 2022. [2] Gottenberg JE, et al. PLoS One. 2013. [3] Jin Xie et al. Trends Immunol. 2003. Acknowledgements: NIL. Disclosure of Interests None Declared.

The link between immune cell function and cell metabolic reprogramming is currently known under the term "immunometabolism". Similarly to the Warburg's effect described in cancer cells, in activated immune cells an up-regulation of specific metabolic pathways has been described and seems to be pathogenic in different inflammatory conditions.Sjӧgren's syndrome (SS) is a systemic autoimmune disease that affects the exocrine glands and is characterised by a progressive loss of secretory function. Despite the increasing amount of evidence on the ability of metabolism in regulating cell behaviour in inflammatory or tumoral conditions, the field of metabolism in SS is still for the most part unexplored.The aim of this review is to summarise currently available studies evaluating cell metabolism in SS with a particular focus on the possible pathogenic role of metabolic changes in immune and non-immune cells in this condition.

OBJECTIVES:To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards.METHODS:For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure.RESULTS:After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries.CONCLUSIONS:Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.

OBJECTIVES Data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis (SV), are limited. The aim of this study was to evaluate the occurrence of a disease flare and the appearance of adverse events (AEs) following administration of anti-SARS-CoV-2 vaccine in a multicentre cohort of patients with SV. METHODS Patients with SV and healthy controls (HC) from two different Italian rheumatology centres were asked to complete a questionnaire assessing disease flares occurrence, defined as new onset of clinical manifestations related to vasculitis needing an implementation of therapy, and local/systemic AEs appearance following anti SARS-CoV-2 vaccination. RESULTS 107 patients with SV (57 ANCA-associated) and 107 HC were enrolled. A disease flare occurred in only one patient (0.93%) with microscopic polyangiitis after the first dose of an mRNA vaccine. After both the first and the second vaccine dose administration, no significant differences in AEs between patients with SV and HC were observed; no serious AEs were reported as well. CONCLUSIONS These data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.

Background The quality of sexual life (QSL) is a complex and multimodal experience influenced by endogenous and external factors, including age, gender, and cultural environment. Rheumatic diseases, with their burden of pain, fatigue, organ damage, and disability, can severely impair sexual life and this is true also for Sjögren’s Syndrome, where simple tools to assess the QSL in everyday clinical practice are needed. Objectives To translate ad adapt into Italian the Qualisex, a new brief questionnaire originally created for Rheumatoid Arthritis patients, for women with primary Sjögren’s Syndrome (pSS) and evaluate the impact of the disease on their sexuality. Methods Consecutive sexually active pSS (according to ACR/EULAR 2016 criteria) patients aged >18 were asked to participate in this study approved by the local bioethics committee. With the permission of the developer, the French original version of the Qualisex questionnaire (consisting of 10 items, the higher the score, the greater the negative impact of the disease on the QSL) was translated and adapted into Italian according to current guidelines. In the absence of a gold standard assessment for sexuality in pSS, face and content validity was assessed cross-sectionally by correlations with other disease aspects such as anxiety and depression measured by Hospital Anxiety and Depression Scale (HADS), EULAR SS patient-reported index (ESSPRI), and quality of the relationship. As a measure of reliability, internal consistency was assessed through Cronbach’s Alpha coefficient. A Cronbach’s value >0.7 is generally regarded as satisfactory. The feasibility of the scale was indirectly assessed through missing data. To assess the factorial structure of the Italian version of the questionnaire an Exploratory Factor Analysis (EFA) was carried out. Moreover we also assessed the level of redundancy by means of intra-item correlation of the Qualisex questionnaire. ESSDAI (EULAR Sjögren’s Syndrome Disease Activity Index), and SSDDI (Sjogren’s Syndrome Disease Damage Index) were assessed as well. Analyses were carried out with IBM SPSS Statistics for Macintosh, version 22.0 (IBM Corp., Armonk, NY, USA). Results 40 sexually active women with pSS and a median age of 53 (IQR 45.25-57.25) were enrolled. The EFA showed that the model with a single factor appeared to be highly significant (Chi235= 2943.10; p<0.05); the average inter-item correlation was found to be 0.392 (Min -0.479; Max 0.834) which is an acceptable value as for redundancy. There were no missing answers. Cronbach’s alpha coefficient resulted to be 0.86 which indicates an adequate internal consistency. The median Qualisex score was 4.65 (IQR 2.13–6.2). As far as correlations, age (Rho=0.39; p<0.05), menopause (Rho=0.41; p<0.05), relationship quality (Rho=0.55; p<0.05), anxiety (HADS-A; Rho=0.38; p<0.05), and depression (HADS-D; Rho=0.47; p<0.05) appeared to be positively correlated with Qualisex score. Also, a positive correlation with ESSPRI (Rho=0.43; p<0.05), and drug use (Rho=0.37; p<0.05) was demonstrated. On the contrary no significant correlation was found with education (Rho=-0.07; p=0.64), systemic disease activity (Rho=0.14; p=0.39), and damage (Rho=0.06; p=0,74). Conclusion The Italian version of the Qualisex questionnaire is a valid, reliable and useful tool to assess the quality of sexual life in pSS. QSL in pSS women has an inverse relationship with age, menopause, drug use, ESSPRI, mood disorders, and dissatisfaction with the partner, while, as previously reported, no correlation was found with disease activity, damage, and educational status. This further highlights the impact of subjective symptoms such as dryness, pain, fatigue, and the overall psychological well-being on patients’ life. Thus, it is critical for the physician to consider patients’ perspective. Disclosure of Interests None declared

Background Vaccinations against SARS-CoV-2 represent a fundamental tool in controlling the pandemic. To date, data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis, are limited. Objectives In this study we aimed at evaluating the safety of anti-SARS-CoV-2 vaccines in a multicentric cohort of patients with systemic vasculitis. Methods Patients with systemic vasculitis from two Rheumatology centres who had received anti-SARS-CoV-2 vaccine were retrospectively examined. The primary outcome was to evaluate, in this multi-centric cohort, the occurence of a disease flare after the administration of the vaccine, defined as development of clinical manifestations related to vasculitis with a concomitant increase in serum inflammatory markers. As a secondary outcome we aimed at evaluating, in a monocentric cohort of patients with vasculitis, the occurrence of adverse events (AEs) following vaccine administration compared to healthy controls (HC). Results We examined 111 patients with systemic vasculitis (n=69 female, n=42 male), with a mean age of 64.3 (± 13) years. Sixty had ANCA-associated vasculitis (AAV), fourty-two had Giant-Cell Arterities (GCA), five had Periarteritis Nodosa, four had Takayasu’s arteritis. One-hundred and five patients received a mRNA vaccine and six a viral vector one. A disease flare occurred in only 2 patients (1.8%) after the first dose of a mRNA vaccine: both had AAV (microscopic poliangioitis) and developed a pulmunary disease flare (respiratory failure requiring hospitalization and treatment with high-dose glucocorticoids). Of note, one of these patients had multiple previous comorbidities, including a severe COPD. Multivaried analysis, adjusted for age and sex, performed in a single monocentric cohort of patients with systemic vasculitis [n=60 (39 AAV, 21 GCA), 37 female, 23 male, mean age 71 (± 12.5) years] demonstrated a statistically significant higher frequency of AEs in vasculitis patients compared to HC (p=0.015) after the first dose of vaccination. No significant differences in the frequency of AEs in vasculitis patients compared to HC after the second dose were detected. All the AEs were mild in both groups (malaise was the most frequently reported); no serious AEs were reported. Conclusion Our data show a very low incidence of disease flares after the administration of anti-SARS-CoV-2 vaccines in patients with systemic vasculitis. Patients with systemic vasculitis seem more prone to develop mild AEs after the first dose of the vaccine. Taken together, this data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis. Disclosure of Interests None declared