ObjectiveThe diagnosis of Sjögren’s Disease (SjD) remains challenging due to the non-specific nature of sicca symptoms and the need for invasive biopsies. This pilot study aimed to investigate the potential of salivary Substance P (SP), a neuropeptide involved in glandular regulation and neurogenic inflammation, as a novel, non-invasive biomarker to differentiate patients with SjD from those with non-autoimmune Non-Sjögren sicca syndrome (NSS).MethodsUnstimulated whole saliva samples were collected from three groups of female participants: 13 patients classified as SjD according to ACR/EULAR criteria, 13 patients with idiopathic NSS symptoms who did not meet the criteria, and 13 healthy controls (CTRL). Salivary SP concentrations were measured using a specific enzyme-linked immunosorbent assay (ELISA). Clinical, serological, and histopathological data were recorded for correlation analyses. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of salivary SP.ResultsSalivary SP levels were significantly higher in SjD patients (mean 92.2 ± 15.503 pg/ml) compared to both NSS patients (30.39 ± 4.08 pg/ml, p < 0.005) and healthy controls (39.93 ± 5.97 pg/ml, p < 0.005). No significant difference was found between the NSS and CTRL groups. ROC analysis demonstrated that salivary SP could distinguish SjD from NSS, with an area under the curve (AUC) of 0.8225 (p = 0.005). At a cut-off value of 47.63 pg/ml, sensitivity was 77% and specificity was 85%. A positive association was observed between salivary SP levels and the presence of ANA autoantibodies in the SjD cohort.ConclusionSalivary SP appears to be elevated in patients with SjD compared to those with NSS in this preliminary study, suggesting a potential diagnostic signal that warrants further investigation. Although the observed differences hint at possible utility as a non-invasive biomarker related to neuroimmune dysregulation, the diagnostic accuracy observed should be interpreted with caution due to the limited sample size and the exploratory nature of the findings. Larger, prospective, and well-powered studies are needed to confirm these preliminary observations, to assess the robustness of salivary SP as a diagnostic tool, and to determine its potential clinical applicability.

Objectives Smoking is recognised as one of the strongest environmental risk factors for the development of rheumatoid arthritis (RA). Cigarette smoke increases protein post-translational modifications (PTMs), including citrullination and carbamylation, involved in the pathogenetic mechanisms of RA. Recently, tobacco companies developed new products, such as iQOS, a heat-not-burn cigarette (HNBC), which are becoming increasingly used. To date, only two epidemiological studies have been conducted in the rheumatology field. However, no studies are available on the effects of HNBCs on the pathogenic mechanisms involved in rheumatic diseases. We aimed to evaluate whether HNBCs are associated with an increase in PTMs and their effects on cell death mechanisms, such as apoptosis.Methods Human bronchial cells (BEAS-2B) were treated with cigarette smoke extracts from traditional cigarettes (TC) and HNBC. Western blot was performed to assess protein citrullination and carbamylation, while apoptosis was assessed by flow cytometry, after staining with annexin V-FITC/PI and western blot through enzyme Parp1 evaluation.Results The exposure of BEAS-2B to HNBC or TC extracts causes significantly increased citrullination and carbamylation of proteins, compared with untreated cells. Furthermore, it leads to an augmentation of apoptosis, evaluated through annexin V-FITC/PI and enzyme Parp1 levels.Conclusion Our results show that the extracts of HNBC and TC increase citrullination, carbamylation and influence cell death, causing an activation of apoptosis. This is the first study showing the effects of HNBC on PTMs and cell death mechanisms, raising alarm about the safety of these smoking alternatives in rheumatology. These data allow us to speculate that HNBC, like TC, could represent a risk factor for the development of RA in genetically susceptible individuals.

OBJECTIVE:Sjögren disease (SjD) is a systemic autoimmune disease characterized by increased risk of B-cell non-Hodgkin lymphoma. Although cryoglobulinemia and serum monoclonal component (MC) are well-recognized paraproteinemias in SjD, no large-scale study has directly compared their isolated and combined impact on phenotype and lymphoproliferative risk. METHODS:A retrospective, multicenter, cross-sectional study was conducted within the Italian GRISS registry. Patients with SjD were stratified into four groups: isolated monoclonal gammopathy (MC-alone), isolated cryoglobulinemia (CRYO-alone), both (MC+CRYO), or neither (controls). Demographics, lymphoma history, ever-documented ClinESSDAI domains, and laboratory lymphoproliferative risk-related markers were analyzed. Primary and secondary outcomes assessed lymphoma diagnosis and the distribution of laboratory lymphoproliferative risk-related markers and ClinESSDAI domains across groups, with associations tested using logistic regression adjusted for confounders. RESULTS:1202 SjD patients were enrolled: 58 (4.83%) in the MC-alone, 32 (2.66%) in the CRYO-alone, 35 (2.91%) in the MC+CRYO, and 1077 (89.60%) controls. Compared with controls, only the MC+CRYO group showed significant association with lymphoma (OR 6.30, 95%CI 2.66-14.92; p < 0.001), while MC-alone and CRYO-alone were not associated. Cryoglobulinemia, alone or combined with MC, correlated with laboratory lymphoproliferative risk-related markers such as rheumatoid factor (p < 0.001) and low C4 (p < 0.001), and with ClinESSDAI vasculitic features (cutaneous [p < 0.001], renal [p < 0.05], PNS [p < 0.001]). The MC+CRYO group additionally displayed a lymphoproliferative phenotype correlating with constitutional (p < 0.05), glandular (p < 0.05), hematological (p < 0.001), and lymphadenopathy (p < 0.001) domains. CONCLUSION:Cryoglobulinemia in SjD associates with vasculitic disease activity, whereas the coexistence of serum MC and cryoglobulins identifies a distinct, high-risk subset characterized by advanced B-cell expansion and increased lymphoma susceptibility.

Objectives To evaluate whether early canakinumab initiation may provide treatment advantages in Still’s disease (SD) patients, particularly in terms of therapy discontinuation due to long-term disease remission, glucocorticoid sparing effect, and increase in the frequency of monocyclic disease course rather than a polycyclic or chronic articular pattern. Methods SD patients treated with canakinumab were grouped according to time between disease onset and canakinumab initiation (≤3 months vs. >3 months). Patients were enrolled from the international AutoInflammatory Disease Alliance (AIDA) Network registry for SD. Results Overall, 190 patients were enrolled, 35 (19%) treated with canakinumab within three months from SD onset and 155 (82%) starting canakinumab later. Glucocorticoids use decreased more rapidly in patients receiving canakinumab within 3 months from SD onset than among patients treated later, with reductions of 50% vs 6% at month 3 (p=0.0001), and 75% vs 32% at month 6 (p=0.004). In logistic regression analysis, canakinumab initiation within 3 months from disease onset was significantly associated with treatment discontinuation due to long-term remission (OR 4.83, 95% CI 1.08-23.19; p=0.04). A monocyclic course occurred in 49% of patients starting canakinumab ≤3 months versus 8% starting later (p<0.0001). Starting canakinumab within 3 months from disease onset was significantly associated with a monocyclic disease course compared with the chronic-articular (RRR 4.43, 95% CI 1.12-17.60; p=0.034) and polycyclic courses (RRR 8.97, 95% CI 1.29-62.3; p=0.03). Conclusions Early canakinumab initiation is associated with treatment discontinuation due to long-term remission and appears linked to a greater frequency of a monocyclic disease course.

Objective. To assess the adherence to the vaccination campaign against SARS-CoV-2 in patients with immunoglobulin-G4-related disease (IgG4-RD) and to evaluate the development of local and systemic adverse events (AEs) following vaccination. Additionally, to investigate the rate and outcome of SARS-CoV-2 infection in IgG4-RD patients. Methods. Patients with IgG4-RD in follow-up before the onset of the SARS-CoV-2 pandemic were contacted by telephone and asked to answer an ad hoc questionnaire regarding their vaccination status against SARS-CoV-2 and related AEs following vaccination. The occurrence and the outcome of SARS-CoV-2 infection were also recorded. The same questionnaire was proposed to healthy controls (HC). Results. 20 patients and 40 HC were enrolled. In the patient’s cohort, 90% were vaccinated with at least one dose; among them, 9 reported AEs: 44.4% systemic and 22.2% local. Within the HC group, 100% were vaccinated with at least one dose. 13 out of 40 HC had systemic AEs (50%), and 27 (67.5%) reported local AEs. Neither in IgG4-RD nor in HC, serious adverse reactions were observed. Among the patient’s cohort, 60% contracted SARS-CoV-2 infection, and 41.67% were on immunosuppressants at the time of the infection. One patient presented with severe COVID-19. No disease flares following vaccination or infection were reported. Conclusions. Results from our study indicate a good adherence to the vaccination campaign against SARS-CoV-2 in patients with IgG4-RD and support a relatively good safety profile of this vaccine. Compared to controls, patients with IgG4-RD reported slightly more systemic AEs and fewer local AEs. A similar rate of COVID-19 development was observed between IgG4-RD patients and HC.

OBJECTIVES:The phenotype of Sjögren's disease (SjD) may be influenced by several variables. Among these, the role of patient geolocation has been poorly explored. The study compared epidemiologic, serologic, clinical features and comorbidities according to geographical origin in a large Italian multicentre SjD cohort. METHODS:This is a retrospective analysis of a multicentre SjD cohort (2016 ACR/EULAR criteria) consecutively included in the Italian SjD Study Group registry and grouped into three macrogeographic areas: North, Centre and South. Disease-specific epidemiologic, serologic, histologic and clinical variables were collected. Comorbidities, traditional cardiovascular (CV) risk factors and history of CV events were also recorded. All data were stratified by geographic area to assess regional differences. RESULTS:1231 SjD patients, median 53 (42-63) years at diagnosis and 95% females, were included. No differences were observed in sex distribution or ethnicity among the three areas. Patients from the South had older age at diagnosis compared to the North (55 vs. 51 years, p=0.001) and Centre (55 vs. 51 years, p=0.002) and higher frequency of activity in the constitutional and articular but lower in biological domains (p<0.001 for all). Hypertension and hypercholesterolaemia were more prevalent in the Centre and obesity was more common in the South compared to the North (p<0.001). No significant differences were observed in other CV risk factors and CV events. CONCLUSIONS:This study provides the first evidence of geo-epidemiological differences among Italian SjD patients, highlighting how geographic origin is associated with disease phenotype and comorbidities. These regional disparities likely reflect environmental, socio-cultural and healthcare system-related factors, underscoring the need for personalised disease management strategies.

OBJECTIVES:Sjögren disease (SjD) predominantly affects females, but the early disease presentation in male patients remains poorly characterised due to historically small sample sizes. The aim of this study was to investigate sex‑based differences in the clinical phenotype at diagnosis of SjD and identify predictors of patient sex using a large international cohort and AI‑enhanced analysis. METHODS:Cross-sectional analysis of an anonymised dataset comprising 17,416 worldwide patients fulfilling the 2002/2016 classification criteria (Sjögren Big Data Registry). We stratified the dataset by sex and conducted a comparative analysis of baseline glandular and systemic involvement, organ-specific ESSDAI domains, and immunological profiles. Multivariate logistic regression models were developed, adjusting for epidemiological confounders (age and ethnicity) to identify predictors of sex classification. We used a generative AI (OpenAI's GPT-4o model) environment with Python (version 3.9) and the pandas (1.4.3), numpy (1.21.5), and matplotlib (3.5.1) libraries. All analyses adhered to GDPR standards, with anonymized patient data and strictly controlled secure environments. RESULTS:The cohort included 1,161 (6.67%) men and 16,255 (93.33%) women, with a mean age at diagnosis of 51.11 years (SD=14.45). Men showed a higher mean age at diagnosis (54.09 vs. 51.42 years in women; t=6.08, p<0.0001), a higher average ESSDAI score (7.65 vs. 5.93; t=7.91, p<0.0001) and higher frequencies in severe DAS categories (i.e. high activity 20% vs. 12% in women, χ² = 81.15, p<0.0001). The epidemiologically-adjusted logistic regression model (pseudo R-squared value of 0.026) identified statistical significance for age (coefficient =0.009, p=0.024; each additional year in age increased the likelihood of being female by 1.4%), ethnicity (coefficient=0.579, HR=1.78, p=0.004), ocular dryness (coefficient=-0.607, HR=0.54, p<0.001), and systemic activity in the glandular (coefficient=0.359, HR=1.43, p=0.006) and pulmonary (coefficient=0.445, HR=1.56, p=0.004) ESSDAI domains. CONCLUSIONS:Male SjD patients present a distinct, more systemic phenotype at diagnosis. Awareness of sex‑specific features can improve early recognition and tailored management.

OBJECTIVES:This study aimed to analyse the relationship between distinct autoantibody combinations (immunological signatures) and systemic disease activity in patients with Sjögren's disease (SjD). The hypothesis was that specific multi-autoantibody signatures would be associated with higher systemic disease activity at diagnosis, serving as predictors of a more severe disease course. METHODS:A retrospective observational study was conducted using data from the Big Data Sjögren Project Consortium, an international multicentre registry. The serological status (positive/negative) at diagnosis for ANA, RF, anti-Ro, and anti-La was recorded for each patient. Systemic disease activity was assessed using the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and a simplified Disease Activity Score (DAS) categorised as low, moderate, or high. Statistical analyses included pairwise comparisons, a sensitivity analysis grouping signatures by the number of positive antibodies, and demographic-adjusted ordinal models. RESULTS:Serum autoantibodies were highly prevalent, with over 94% of patients having at least one autoantibody. The mean ESSDAI values varied significantly across signatures. The fully seronegative group had the lowest mean ESSDAI at 3.61, while the fully seropositive group (ANA+/Ro+/La+/RF+) had the highest among common phenotypes, with a mean of 7.93. A strong dose-response relationship was observed, with each additional positive autoantibody associated with a 1.11-point mean increase in ESSDAI and a 35% increase in the odds of being in a higher DAS category. The rarest signatures, such as ANA-/Ro-/La+/RF+, exhibited the highest mean systemic activity (mean 13.20). CONCLUSIONS:The number and combination of SjD-related autoantibodies at diagnosis are robustly associated with systemic disease activity. Multi-positive profiles, particularly those combining RF with anti-Ro, identify patients at higher risk of systemic activity. Interpreting combined serological patterns offers an immediate, low-cost method for patient stratification and can help guide clinical management.

Background: Sjögren disease (SjD) is a chronic autoimmune disorder characterized by inflammation of the exocrine glands, particularly the salivary and lacrimal glands, leading to dryness of the eyes and mouth. Current therapeutic options for SjD are empirical, due to the lack of evidence-based recommendations. However, off-label use of biologics or small molecules, particularly B-cell targeted therapies, is applied in some clinical scenarios in SjD. Research on the use of targeted therapies in SjD is ongoing, and several clinical trials are exploring their efficacy. Objectives: To analyse the off-label use of biologic and small molecule therapies in treating complicated/severe SjD using real-world data. Methods: The Big Data Project Consortium is an international, multicentre registry created in 2014. The inclusion criteria were the fulfilment of the 2002/2016 classification criteria. By December 2023, the participant centers had included 16703 valid patients from 28 countries. We have retrospectively analysed the use of biological and small molecule therapies in SjD, including the pharmacological classification of the used drugs, therapeutic indications, sequential and combination use, and causes of mortality. Results: The use of biologics and small molecules was reported in 330 (2%) patients, who received 359 therapeutic courses. We identified 23 different therapies that overwhelmingly consisted of B-cell targeted drugs (83%); more rarely, the drugs used targeted T cells (8%), tyrosine kinases (2.5%), TNF (2.5%), cytokines (2%), integrins (0.6%), and complement (0.3%). B-cell targeted therapies overwhelmingly consisted of rituximab (79%), followed by belimumab (4%), and isolated cases of use of obinutuzumab and ofatumumab (<1%). T-cell targeted therapies included the use abatacept (8%); a large list of other biologics and small molecule inhibitors (16 different drugs) were used in less than 5 cases per drug. Combined biologic therapies were reported in only four patients (belimumab plus rituximab). The main therapeutic indication consisted of ESSDAI severe involvements that predominantly affected a single organ (57%), followed by the treatment of lymphoma (23%), and by severe systemic multiorgan involvement (18%). According to the predominantly affected ESSDAI domain, besides lymphadenopathy, the most frequent indications included articular (20%), pulmonary (7%), PNS (6%), CNS (6%), and cutaneous (5%) involvements (Figure 1). Death was reported in 32 patients (10%), with the most frequent causes being infection (34%) and cancer progression (31%). It should be noted that 4 (36%) of the 11 patients who died from infection were caused by COVID-19 (all of them were under treatment with rituximab). Conclusion: The real-life use of biologic and small molecule therapies in patients with SjD is exceptional (2%), a fact closely related to their off-label use in most therapeutic indications. Nearly 85% of therapies are directed against B cells (overwhelmingly rituximab), with exceptional cases of new anti-CD20 monoclonal antibodies or combined therapy with rituximab and belimumab. Mortality is higher than expected in SjD treated with the biologic and small molecule therapies [1], infections (notably COVID-19 in patients treated with rituximab) and cancer progression being the most frequent causes of death, thus highlighting the need for defining advanced treatment indications in SjD. REFERENCES: [1] Brito-Zeron P, et al. EClinicalMedicine. 2023; 61(4):102062. doi: 10.1016/j.eclinm.2023.102062 Acknowledgements: MD Juliana Viana Baiao Lemos, collaborator from Rheumatology Department, Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto Universidade de Sao Paulo, Brazil. Disclosure of Interests: None declared.Figure 1

Aseptic abscesses syndrome is a rare but increasingly recognized disease that falls within the spectrum of autoinflammatory disorders. Here, we describe the case of a patient who presented with abdominal pain and fever, along with multiple abdominal and extra-abdominal abscesses, in the absence of underlying hematologic, autoimmune, infectious, or neoplastic conditions. Initially, the patient responded to glucocorticoids, but experienced several flares upon discontinuation, leading to the initiation of treatment with a TNFα inhibitor. After 5 years, an attempt to discontinue treatment resulted in a new flare of the disease. Remission was eventually achieved with a biosimilar TNFα inhibitor, albeit requiring shortened infusion intervals.

Objective. Data from trials demonstrated that abatacept (ABA) has a good safety and efficacy profile in treating rheumatoid arthritis. We have studied the retention rate of ABA in a real-life cohort of patients with rheumatoid arthritis. Methods. This is a monocentric, retrospective study including patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism 2010 criteria who started treatment with ABA. The Kaplan-Meier method was applied to evaluate the ABA retention rate. Results. This analysis was conducted on 161 patients [male/female 21/140, median age 65 years, interquartile range (IQR) 18.7, median disease duration 169 months, IQR 144.0]. 111 patients (68.9%) received ABA subcutaneously. ABA was associated with methotrexate in 61.9% of patients and was the first biological disease-modifying antirheumatic drug in 41%. We observed a median ABA survival of 66 months [95% confidence interval (CI) 57.3-74.7], with a retention rate of 88% at 6 months and 50.9% at 5 years. Drug survival was significantly higher in patients treated with ABA subcutaneously and in male patients (p=0.039 and p=0.018, respectively). Adjusted for main confounders, female gender was the main predictor of withdrawal (hazard ratio 5.1, 95% CI 1.2-21.3). Conclusions. Our study shows that better survival is associated with subcutaneous administration and male gender, confirming ABA effectiveness.

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.

OBJECTIVES:The aim of this work is to review the existing literature regarding sexual and reproductive function of women affected by systemic sclerosis and to establish the impact of the disease on the gynaecological-obstetrical field. METHODS:A systematic search has been conducted by means of PubMed, Cochrane, Google Scholar, until January 2024 by the keywords ''systemic sclerosis'', ''fertility'', "sexual dysfunction" and "pregnancy". RESULTS:Sexual dysfunction has been described in most of the studies. This could be related to dryness and dyspareunia, but also to the psychosocial impact of SSc on body and facial appearance, which impacts on social and sexual relationships. There is conflicting evidence regarding the influence of SSc and fertility. Before the 1980s pregnancies in these patients were rare. This could be linked to the satisfied reproductive desire before the onset of SSc, or to the fact that pregnancy was labelled as high-risk, leading to counsel against it in most patients. Recently, the evidence supporting infertility is conflicting. There is no certain theory on how the disease may interfere with reproductive function, but a possible linkage can be detected in a pro-inflammatory milieu which can impair the ovarian reserve. CONCLUSIONS:Women affected by SSc should be followed-up by a multidisciplinary team to prevent sexual dysfunction. Although there is no consensus on the impact of SSc on fertility, these patients should be provided with adequate pre-conceptional counselling and a strict follow-up in high-risk pregnancy units.

Background: Fibromyalgia (FM) is one of the most common causes of chronic widespread pain. Although pain is the most distinctive feature of this syndrome, FM is characterized by a complex polysymptomatology that also comprises fatigue, sleep disturbances and other functional symptoms that negatively affect the overall quality of life. Since FM can negatively affect personal well-being, self-image and interpersonal relationship, it can also impact sexual functioning and pleasure. When interrogated regarding sexuality, female FM patients answer that it is important for their quality of life and, for the majority of them, it appears as a physical, psychological, emotional and relational need. For these reason, women require support and understanding from both their partners and health care professionals. In this context, the availability of a simple and rapidly administered questionnaire, such as the Qualisex, for the evaluation of sexual disfunction on these patients might be considered an acceptable method of communication of this sensitive issue. Objectives: The aim of this study was to evaluate sexual disfunctions in a large cohort of FM women through Qualisex questionnaire, which has been originally created for French patients with rheumatoid arthritis and recently adapted and validated to Italian language for FM patients. Methods: In this cross-sectional study, consecutive women with a diagnosis of FM (2016 ACR criteria) referring to our out-patients Fibromyalgia Clinic were asked to answer an anonymous online survey, including demographic characteristics, medical and pharmacological history, Hospital Anxiety and Depression Scale (HADS) and Qualisex questionnaire for sexual dysfunction. Results: The cohort enrolled in this study was composed by 489 FM women, median age 50. The results of the univariate analysis showed a worse sexual functioning in women with lower educational level, housekeepers and retired patients but also in women who referred a concomitant diagnosis of chronic pelvic pathology or a psychiatric disorder. Among women who were in an active relationship, the referred sexual understanding with the partner was inversely associated with sexual functioning. Finally, the consumption of drugs known to be associated with a reduction of sexual desire resulted significantly associated with a worse sexual functioning (Table 1). The multivariate linear model showed a significant influence of the presence of a partner in women’s life, the referred sexual understanding and the use of drugs associated with a reduction of sexual desire on women’s quality of life (Table 2). Conclusion: Qualisex questionnaire represents a good test to detect the impaired sexuality in FM female patients, to establish a more correct intervention, pharmacological, psychotherapeutic (single or couple) and supportive, reducing the destructive circle that FM and poor sexual quality determine. Different aspects contribute to sexual dysfunction, with an important impact of FM on sexual quality and consequently a worsening of FM symptoms. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: Recent studies have demonstrated that different types of cells express surface glycosylated RNA (glicoRNA). Through this mechanism, they are exposed to the extracellular space and, consequently, to the immune system. In particular, a glycosylated surface ds-RNA (glico-dsRNA) has been identified using the anti-dsRNA J2 antibody. Objectives: The purpose of this study was to evaluate the monocytic expression of the glico-dsRNA and correlate it with the clinical and laboratory characteristics of patients with Sjogren Syndrome (SjS). Methods: Ten patients diagnosed with SSj and ten healthy control donors (HD) matched for sex and age were evaluated. Demographic and clinical data were collected from these patients, and venous blood was drawn. Mononuclear cells from peripheral blood (PBMC) were isolated from the blood. RNase A was added to the sample and incubated. After washing, the cells were incubated with anti-dsRNA J2 antibody. Subsequently, the cells were incubated with Goat anti-Mouse-IR 680 antibody. Finally, acquisition was performed using a FACS Calibur flow cytometer and 20,000 events per sample were evaluated. The data were analyzed using Cell Quest Pro software. Titers of anti-Ro60 and Ro52 antibodies were measured using ELISA. Results: The clinical and laboratory characteristics of the patients are summarized in Table 1. Our study revealed that patients with SSj express a higher percentage of glyco-dsRNA on the surface of monocytes (median=38; σ=27.2) compared to HD (median=11; σ=6.1) (p= 0.001) (Figure 1 and 3), and that monocytic expression of glyco-dsRNA correlates with disease activity assessed by ESSDAI (p=0.0001) (Figure 2). Finally, we demonstrated that the expression of glyco-dsRNA on monocytes does not correlate with the antibody titers of antiRo60 (p-value=0.3) and antiRo52 (p-value=0.8). Conclusion: The results demonstrate that the expression of glyco-dsRNA on the cell surface of monocytes is increased in patients with SSj compared to HD and that this expression correlates with disease activity. Therefore, glyco-dsRNA could potentially represent a new surface antigen involved in the pathogenesis of these diseases and serve as a new marker of disease activity. REFERENCES: [1] Small RNAs are modified with N-glycans and displayed on the surface of living cells. Flynn R. et al. Cell 2021 Jun 10;184(12):3109-3124.e22. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: Neurological manifestations can occur in up to half of patients with Sjögren disease (SjD) and the peripheral nervous system (PNS) is the most commonly involved (5-21%). Objectives: To analyze the frequency and phenotypic expression of PNS involvement at the time of SjD diagnosis Methods: The Big Data Project Consortium is an international, multicenter registry created in 2014. Baseline clinical information from leading centers on clinical research in SjD of the five continents was collected as a first step. The centers share a harmonized data architecture and conduct cooperative online efforts to refine collected data under the coordination of a big data statistical team. The inclusion criteria were the fulfillment of the 2002 or 2016 classification criteria. Results: By December 2023, the participant centers had included 16'703 patients from 28 countries (15'602 women, mean age at diagnosis of 51.66 years). PNS involvement at diagnosis, defined according to the ESSDAI classification, was reported in 869 (5.2%) patients. Among them, 518 (60%) showed mild active PNS involvement (pure sensory axonal polyneuropathy, V neuralgia, or proven small fibre neuropathy), 264 (30%) showed moderate involvement (axonal sensory–moto neuropathy, cryoglobulinemic pure sensory neuropathy, mild/moderate ganglionopathy, mild chronic inflammatory demyelinating polyneuropathy -CIDP-, or other cranial nerve involvements), and 87 (10%) showed highly active PNS involvement (severe motor axonal neuropathy, mononeuritis multiplex, severe ataxia due to ganglionopathy, or severe CIDP). Univariate analysis showed that patients with PNS involvement were more frequently men, diagnosed at an older age, white, had a higher frequency of activity in all the 12 ESSDAI domains and more commonly hypocomplementemia and cryoglobulinemia (all P-values <0.001). The multivariate logistic regression model adjusted for age, sex, ethnicity and the ESSDAI domains showed that systemic activity in the constitutional (OR = 1.95; 95% CI, 1.43–2.65), articular (OR = 1.35; 95% CI, 1.06–1.73), renal (OR = 1.92; 95% CI, 1.25–2.96), muscular (OR = 1.89; 95% CI, 1.11–3.24) and CNS (OR = 5.37; 95% CI, 3.18–9.06) ESSDAI domains, as well as low C3 (OR = 1.44; 95% CI, 1.05–1.98) and low C4 (OR = 1.74; 95% CI, 1.27–2.39), were independently associated with a diagnosis of PNS involvement at the time of diagnosis of SjD. Conclusion: Around 5% of patients had PNS involvement at the time of diagnosis of SjD. Patients with PNS involvement showed higher systemic activity in multiple domains (1.3-2 times higher frequency of constitutional, joint, renal, and muscular involvement), especially concerning concomitant CNS involvement (5-fold higher frequency). Hypocomplementemia was the key immunological marker independently associated with PNS involvement. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.