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Objectives To evaluate humoral and cell-mediated response after three doses of BNT162b2 SARS-CoV-2 vaccine in patients with systemic lupus erythematosus (SLE) treated with Belimumab (BLM). Methods SLE patients were vaccinated with three doses of BNT162b2-mRNA vaccine (two-dose primary vaccination, third booster dose after 6 months). The humoral immune response was assessed one and 6 months after the second dose (T1, T2), and 6 months after the booster dose (T3). Serological assay was performed (The Liaison® SARS-CoV-2 TrimericS IgG chemiluminescent). Spike-specific T-cell response was monitored 6 months after the second vaccine dose and the percentage of cytokines producing T cells was assessed by flow cytometry. Results Twelve patients [12F; median age 46 years (IQR 8.25); median disease duration 156 months (IQR 188)] were enrolled. At T1, all patients showed seroconversion (median anti-Spike IgG levels 1610 BAU/mL, IQR 1390). At T2––day of the third dose––a significant reduction of median anti-Spike IgG antibodies levels was observed [214 BAU/mL (IQR 94); p = 0.0009]. Anti-Spike IgG were significantly increased at T3, reaching a median value of 1440 BAU/mL (IQR 1316; p = 0.005). Despite declining humoral immunity, almost 60% of patients mounted a virus-specific CD4 + T-cell response 6 months after primary vaccination. Conclusions BLM does not impair humoral response to primary BNT162b2 SARS-CoV-2 vaccination. During the follow-up, a decline in antibody levels is evident and the third dose is crucial to increase the specific immune response. Finally, we observed a recall T-cell response to the Spike antigen 6 months after the first vaccination cycle.

Scientific literature demonstrated the impairment in cognitive/executive functions and pragmatic language in SLE patients, potentially involving also asymptomatic subjects. The present study focuses on the assessment in an SLE cohort of emotional intelligence, which is an ability regulated by the network of the executive functions, cognitive abilities involved in the initiation, planning, organization, and regulation of achievement-oriented behaviors: with emotional. Thus, emotional intelligence, defined as the ability to reason with emotions, was evaluated in a SLE cohort diagnosed according to the 1997 American College of Rheumatology criteria. As control healthy subjects were enrolled. The Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT), a skill-scale that measures the ability to perform tasks and solve emotional problems, was administered to patients and controls. Second, a group of SLE patients underwent the Visual Thinking Strategies (VTS) method in order to assess the potential impact of art in cognitive skills like critical thinking, problem solving, and emotional intelligence quotient. The protocol also included the evaluation of the improvement of some skills using a validated VTS skill grid. Self-reported scales for anxiety and depression were performed to rule out the influence of mood disorders on emotional intelligence. The present study demonstrated similar quotient scores of emotional intelligence in SLE patients and healthy controls. Furthermore, VTS method could help in improving this cognitive ability in patients, by implementing critical thinking and problem solving, promoting empathy, and improving tolerance to ambiguity and relational capacity.

In the present study, we applied cluster analysis (CA) in SLE patients with joint involvement to identify which disease subset most commonly develops erosive damage.We collected clinical and laboratory data of SLE patients with a clinical history of joint involvement (arthritis/arthralgia). Ultrasonographic assessment was performed at level of MCPs and PIPs joints, to identify erosive arthritis, defined as the presence of erosions in at least one joint. Moreover, we detected RF, ACPA anti-CarP, and Dkk1 serum levels. We applied an unsupervised hierarchical CA to identify the aggregation of patients into different subgroups sharing common characteristics in terms of clinical and laboratory phenotypes.CA included 112 SLE patients (M/F 6/106; median age 45 years, IQR 17; median disease duration 96 months, IQR 165). Arthritis was observed in 82 patients (73.2%) and inflammatory arthralgia in 30 (26.8%). US-detected erosive arthritis was observed in 29 patients (25.9%). CA on clinical and laboratory features allowed the identification of four main clusters: in particular erosive arthritis was located in a cluster including renal and neuropsychiatric involvement, serositis, positivity for ACPA, anti-Carp, anti-Sm, anti-RNP, detectable levels of Dkk1.The application of CA made it possible to better characterise SLE phenotype including erosive arthritis. In particular, feature-driven CA leads to the identification of a more aggressive disease, due to a common pathogenic mechanism.

Background Several data have demonstrated the occurrence of erosive arthritis in Systemic Lupus Erythematosus (SLE) patients. However, a few studies have focused on the pathogenic mechanisms involved in this feature. The implication of oral pathogens has been proved in Rheumatoid Arthritis: in particular, Porphyromonas gingivalis ( Pg), by inducing citrullination, could trigger autoimmune response. Here, we evaluated amount of Pg on the tongue in a cohort of SLE patients with arthritis, focusing on the association with the erosive phenotype. Methods SLE patients with arthritis were enrolled. DAS28 was applied to assess activity. Erosive damage was evaluated by ultrasound at level of MCP (metacarpophalangeal) and PIP (proximal interphalangeals) joints. All subjects underwent a tongue cytologic swab in order to quantify the amount of Pg (real-time PCR). The bacterium expression was obtained from the ratio between the patient’s DNA amount and that obtained from healthy subjects. Results 33 patients were enrolled (M/F 3/30; median age 47 years, IQR 17; median disease duration 216 months, IQR 180): 12 of them (36.4%) showed erosive damage, significantly associated with ACPA positivity ( p = 0.03) and higher values of DAS28 ( p = 0.01). A mean ratio of 19.7 ± 31.1 was found for Pg amount. Therefore, we used Pg mean values as threshold, identifying two groups of patients, namely, high Pg and low Pg. Erosive damage was significantly more frequent in high Pg patients in comparison with low Pg (60.0% vs 26.0%, p = 0.001). Furthermore, high Pg patients showed higher prevalence of skin manifestations, serositis, and neurological involvement ( p = 0.005, p = 0.03, p = 0.0001, respectively). Conclusion The possible contribution of oral microbiota in SLE erosive arthritis was here evaluated for the first time, finding a significant association between erosive damage and higher expression of Pg at tongue level.

Musculoskeletal involvement is one of the most common manifestations of systemic lupus erythematosus (SLE), with a negative impact on both quality of life and overall prognosis. SLE arthritis can be classified into three different subtypes, with different prevalence and characteristic biomarkers and MRI findings. Identifying the pathogenetic mechanisms underlying musculoskeletal manifestations’ development is crucial to develop therapeutic strategies to suppress synovial inflammation, prevent erosions and deformities, and improve SLE patients’ quality of life. Hence, here we discuss the main pathogenetic mechanisms and therapeutic approaches of musculoskeletal manifestations of SLE from the 2022 International GISEA/OEG Symposium.

Systemic lupus erythematosus (SLE)–related arthritis has been traditionally defined as non-erosive and is therefore considered a minor manifestation requiring a mild treatment. However, the concept of non-erosive arthritis in SLE has been challenged with the advent of sensitive imaging techniques, such as high-resolution ultrasound with power Doppler or magnetic resonance. The application of these new imaging tools has demonstrated that up to 40% of SLE patients with joint involvement can develop erosive damage. Thus, this more aggressive phenotype can be identified not only in patients overlapping with rheumatoid arthritis (RA). This issue has been considered for the first time in the classification criteria proposed by Systemic Lupus International Collaborating Clinics in 2012, in which the old definition of “non-erosive arthritis” was replaced with either synovitis or tenderness in two or more joints with morning stiffness, suggesting the possible presence of an erosive phenotype. Accordingly, the 2019 EULAR/ACR’s SLE recommendations advise treatment with immunosuppressant or biological drugs for patients with RA-like moderate arthritis. As a result, several studies have investigated the presence of biomarkers associated with SLE erosive damage. A relevant role seems to be played by the autoantibodies directed against post-translational modified proteins: above all, a significant association has been observed with antibodies directed against citrullinated and carbamylated proteins. Conversely, the rheumatoid factor was not associated with this more aggressive SLE-related arthritis. Nonetheless, some pro-inflammatory factors have been associated with erosive damage in SLE patients. These results suggest new pathogenic mechanisms underlining erosive arthritis, only partially shared with RA. Hence, in the present narrative review, we summarized available data about erosive arthritis in SLE patients, in the light of its impact on therapeutic decisions.

Objective The EULAR recommendations underline the use of MMF for Lupus Nephritis (LN) but also for the treatment of moderate/severe non-renal manifestations (NLN). This study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a SLE cohort in a real-life scenario. Secondly, we investigated the MMF influence to control chronic damage progression. Methods We performed a longitudinal study including all the SLE patients starting MMF in our Lupus Clinic (from 2008 to 2020). The DRR was estimated using the Kaplan-Meier method. Results We evaluated 162 SLE patients (M/F 22/140). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%) followed by NPSLE (10, 6.2%) and other manifestations (12, 7.4%). We registered a median treatment duration of 30 months (IQR 55). At 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (60.5%). The DRR was higher in the subgroup of patients with joint involvement (75.4%, P non-significant). During the overall observation period, 92 patients (59.2%) discontinued MMF. The main cause of withdrawal was the achievement of remission, observed in 20 patients (21.7%). Moreover, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in the median SDI values (baseline: 0.6, IQR 1; last: 0.93, IQR 1). Conclusions Our finding suggested that MMF is a safe and effective drug for SLE manifestations other than LN, especially for joint involvement. Moreover, it was able to control the chronic damage progression.

Objective We investigated the genetic diversity, molecular epidemiology and evolutionary dynamics of Staphylococcus aureus (SA) isolated from SLE patients by means of phylogenetic analysis. Methods Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of the translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate relationships and to assess significant clades. Selective pressure analysis was used to investigate the evolution of the SA tuf gene. The gene sequences from non-SLE individuals, downloaded from the GenBank database, were compared through phylogenetic analysis with the tuf gene from SLE patients. Results We enrolled 118 patients [M/F 10/108; median (interquartile range (IQR)) age 45.5 (13.2) years; median (IQR) disease duration 120 (144) months]. Twenty-four patients (20.3%) were SA carriers (SA+), three of them MRSA. SA+ SLE showed significantly higher SLEDAI-2k values [SA+: median (IQR) 2 (3.75); SA−: 0 (2); P = 0.04]. The phylogenetic analysis, restricted to 21 non-MRSA SA+, revealed a statistically supported larger clade (A, n = 17) and a smaller one (B, n = 4). Patients located in clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, P Conclusion We suggest a possible role of SA nasal carriage status in SLE disease activity. Moreover, our findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.

Objectives We evaluated a monocentric SLE cohort in order to assess the frequency of Lupus comprehensive disease control (LupusCDC), a condition defined by the achievement of remission and the absence of damage progression. Methods Our longitudinal analysis included SLE patients with 5-years follow-up and at least one visit per year. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and three different remission levels were evaluated (Complete Remission, CR; Clinical remission off-corticosteroids; clinical remission on-corticosteroids). Chronic damage was assessed according to SLICC Damage Index (SDI). LupusCDC was defined as remission achievement for at least one year plus absence of chronic damage progression in the previous one year. A machine learning based analysis was carried out, applying and comparing Nonlinear Support Vector Machines (SVM) models and Decision Trees (DT), whereas features ranking was performed with the ReliefF algorithm. Results We evaluated 172 patients [M/F 16/156, median age 49 years (IQR 16.7), median disease duration 180 months (IQR 156)]. SDI values (baseline mean±SD 0.7 ± 1.1) significantly increased during the follow-up period. In all time-points analyzed, LupusCDC including CR was the most frequently detected. The failure to reach this condition was significantly associated with renal involvement and with the intake of immunosuppressant drugs and glucocorticoid (GC). Ten patients (5.8%) have maintained LupusCDC during the whole 5-year follow-up: these patients had never presented renal involvement and showed lower prevalence of anti-phospholipid antibodies (p = 0.0001). Finally, the prevalence of GC intake was significantly lower (p = 0.0001). The application of machine learning models showed that the available features were able to provide significant information to build predictive models with an AUC score of 0.703 ± 0.02 for DT and 0.713 ± 0.02 for SVM. Conclusions Our data on a monocentric cohort suggest that the LupusCDC can efficaciously merge into one outcome SLE-related disease activity and chronic damage in order to perform an all-around evaluation of SLE patients.

Background: The COVID-19 pandemic contributes to the burden of living with different diseases, including Systemic Lupus Erythematosus (SLE). We described, from a narrative point of view, the experiences and perspectives of Italian SLE adults during the COVID-19 emergency, by distinguishing the illness experience before and after the lockdown. Methods: Fifteen patients were invited to participate. Illness narratives were collected between 22 and 29 March 2020 using a written modality to capture patients’ perspectives before and after the COVID-19 lockdown. We performed a two-fold analysis of collected data by distinguishing three narrative types and a qualitative analysis of content to identify the relevant themes and sub-themes reported. Results: Eight narratives included in the final analysis (mean length 436.9 words) have been written by eight females (mean age 43.3 ± 9.9 years, mean disease duration 13.1 ± 7.4 years). Six patients provided a quest narrative, one a chaos and the remaining one a restitution narrative. By text content analysis, we identified specific themes, temporally distinct before and after the lockdown. Before COVID-19, all the patients referred to a good control of disease, however the unexpected arrival of the COVID-19 emergency broke a balance, and patients perceived the loss of health status control, with anxiety and stress. Conclusions: We provided unique insight into the experiences of people with SLE at the time of COVID-19, underlining the perspective of patients in relation to the pandemic.

Belimumab was the first biological drug approved for the treatment of systemic lupus erythematosus (SLE) patients. Phase II/III randomized controlled trials and real-life studies identified patients with musculoskeletal involvement as best responders.To evaluate the effectiveness of belimumab in SLE-related joint involvement.The cohort comprised SLE patients receiving belimumab for musculoskeletal indications. Belimumab was intravenously administrated according to protocols; all the patients were evaluated at baseline (T0) and after 3 (T1), 6 (T2), and 12 (T3) months. We assessed joint activity by disease activity score 28, simple disease activity index (SDAI), clinical disease activity index (CDAI), and swollen tender ratio. Each patient underwent musculoskeletal ultrasound of 34 joints to assess synovial effusion synovial hypertrophy, and power Doppler; by using a semi-quantitative scale (0-3) we obtained the total inflammatory score (0-216).We evaluated 20 patients (males/females 1/19, median age 45 years [interquartile range (IQR) 12], median disease duration 144 months [IQR 144]). CDAI and SDAI significantly decreased at T1 (P = 0.02 and P = 0.01 respectively) and this improvement was maintained at the following time-points (CDAI: T2 P = 0.008, T3 P = 0.004; SDAI: T2 P = 0.006, T3 P = 0.01). A significant reduction of median ultrasound score was identified at T1 (T0 20.5 [IQR 13.5] vs. T1 7.5 [IQR 4.7], P0.001), and maintained at T2 (7.0 [IQR 5], P0.0001), and T3 (7.0 [IQR 9.0], P0.0001).Belimumab induces a sustained improvement of ultrasound-detected inflammatory status at the articular level.

Introduction Joint involvement represents the major determinant in quality of life (QoL)in Systemic Lupus Erhytematosus (SLE) patients. However, QoLhas been generally evaluated by non-specific questionnaires. We evaluated the relationship between SLE musculoskeletal manifestations and QoL, assessed by LupusQoL. Methods Patients with joint involvement (group A) were compared with those without this feature (group B). Disease activity was assessed by SLEDAI-2k in the whole population, while DAS28 and swollen to tender ratio were applied to assess joint activity. LupusQoL was administered to all the patients. Results Group A included 110 patients [M/F 8/102; median age 49 years (IQR 13), median disease duration 156 months (IQR 216)], group B 58 [M/F 11/47; median age 40 years (IQR 15), median disease duration 84 months (IQR 108)].We found significanlty lower values in all the LupusQoL domains except for one (burden to others) in group A in comparison with group B. A significant correlation between DAS28 values and all the LupusQoL domains in group A was found; only three domains correlated with SLEDAI-2k. Conclusions SLE-related joint involvement significantly influences disease-specific QoL. DAS28 better correlated with LupusQoL domains in comparison with SLEDAI-2k, confirming the need for specific musculoskeletal activity indices.

Objective Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor. In vitro dose-dependent treatment with caffeine down-regulates mRNA levels of key inflammation-related genes in peripheral blood mononuclear cells. So far, no robust data are available about the possible contribution of caffeine in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokine serum levels. Methods We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K). Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided into four groups according to the daily caffeine intake: 376.6 mg/day (group 4). At the end of questionnaire filling, blood samples were collected from each patient to assess cytokine levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFNγ, IFNα and BLyS. Results We enrolled 89 consecutive SLE patients. We observed a negative correlation between caffeine consumption and disease activity, measured with SLEDAI-2K. A significantly higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementaemia and anti-dsDNA positivity was observed in patients with a low intake of caffeine. Furthermore, patients with a low intake of caffeine were more frequently treated with glucocorticoids. Regarding cytokine analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found ( p = 0.03, r = –0.2); furthermore, patients with a high intake of caffeine showed lower serum levels of IFNα ( p = 0.02), IL-17 ( p = 0.01) and IL-6 ( p = 0.003). Conclusions In this report we demonstrated the impact of caffeine on SLE disease activity status, as confirmed by the inverse correlation between its intake and both SLEDAI-2K values and cytokine levels. Moreover, patients with a low caffeine consumption seem to have a more severe disease phenotype.

Background:Systemic Lupus Erythematosus (SLE) related arthritis has been traditionally defined non-erosive and then considered a minor manifestation. Thanks to the application of more sensitive imaging techniques, such as ultrasonography (US), erosive damage has been identified in up to 40% of SLE patients with joint involvement, suggesting the need for more appropriate treatment (1). Antibodies directed against citrullinated and carbamilated proteins (ACPA and anti-CarP, respectively) have been associated with erosive damage and then proposed as biomarkers for this more aggressive phenotype (2).Objectives:Here, we evaluated a large SLE cohort with joint involvement by using cluster analysis, in order to identify the disease phenotype associated with erosive arthritis.Methods:For this analysis, we enrolled consecutive SLE patients (ACR 1997 criteria) with a clinical history of joint involvement (arthritis/arthralgia). Clinical and laboratory data were collected in a standardized computerized electronically filled form, including demographics, past medical history with the date of diagnosis, co-morbidities, previous and concomitant treatments, serological status. The presence of rheumatoid factor (RF), ACPA and anti-CarP was investigated by ELISA test. Erosive damage was assessed by ultrasonography at level of metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints (MyLab Eight Exp, Esaote, Florence, Italy). Data have been analysed by hierarchic cluster analysis (SPSS program, IBM).Results:We enrolled 203 patients [M/F 12/191, median age 46.0 years (IQR 18); median disease duration 120.0 months (IQR 108)]. Erosive damage was identified in 53 patients (26.1%), all of them referring at least one episode of arthritis during disease course. Moving on autoantibodies status, RF was positive in 29.5%, anti-CarP in 28.5% and ACPA in 11.2%. The univariate analysis demonstrated a significant association between US-detected erosive damage and anti-CarP (p=0.01), ACPA (p=0.03), and renal manifestations (p=0.03). In Figure 1 we reported the dendrogram obtained from cluster analysis, allowing the identification of four cluster. Positivity for ACPA, anti-CarP, erosive damage, Jaccoud’s arthropathy and renal manifestations were allocated in the same cluster. Interestingly, RF resulted allocated in a different cluster, including ENA, anti-SSA and anti-SSB antibodies.Conclusion:The application of cluster analysis allowed the identification of a specific SLE phenotype, characterized by erosive damage, renal manifestations and positivity for anti-CarP and ACPA. We could speculate about the presence of a shared pathogenic mechanism, involving NETosis, contributing to nephritis and erosive arthritis.References:[1]Ceccarelli F et al. Semin Arthritis Rheum 2017[2]Ceccarelli F et al. Arthritis Res Ther 2018Disclosure of Interests:Fulvia Ceccarelli: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, enrica cipriano: None declared, Carmelo Pirone: None declared, Giulio Olivieri: None declared, Tania Colasanti: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

Background:Joint involvement is one of the most common features observed in Systemic Lupus Erythematosus (SLE), potentially involving up to 90% of patients [1]. Several patients’ reported outcomes (PROs) have been employed to measure Quality of life (QoL) in SLE patients, but frequently not specifically developed for SLE patients. More recently, the LupusQoL has been validated, a disease specific questionnaire[2,3].Objectives:We focused at assessing the relationship between musculoskeletal manifestations and QoL in a large SLE cohort, by using the LupusQoL.Methods:SLE patients with a clinical history of joint involvement (arthralgia/arthritis – group A) were enrolled in the present study. SLE diagnosis was performed according to the revised 1997 ACR criteria. As a control group, we enrolled SLE patients without history of joint involvement (group B).Disease activity was assessed by the SLE Disease Activity Index-2000 (SLEDAI-2k). The activity of joint involvement was assessed by using the disease activity score on 28 joints (DAS28ESR). The LupusQoL was administered to the enrolled patients (Group A and Group B). It consists of 34 items referring to eight domains: physical health (PH), pain (P), planning (PL), intimate relationships (IR), burden to others (BO), emotional health (EH), body image (BI) and fatigue (F).Results:Group A included 110 patients [M/F 8/102; median age 49 years (IQR 13), median disease duration 156 months (IQR 216)], while group B included 58 patients [M/F 11/47; median age 40 years (IQR 15), median disease duration 84 months (IQR 108)]. Group A showed a significantly lower disease duration and mean age in comparison with group B (P< 0.001 for both comparisons). As represented in figure 1, group A showed significantly lower values in all LupusQoL domains except for “burden to others” domain. Moreover, we observed an inverse correlation between DAS28ESRand all the LupusQoL domains in group A patients [PH (r=-0.5, P>0.0001), P (r=-0.5, PFigure 1.Conclusion:In the present study, by using a disease specific PRO, we found a poorer QoL in SLE patients with joint involvement in comparison with those without this manifestation. Moreover,DAS28ESRsignificantly correlated with all LupusQol domains, differently from SLEDAI-2k, suggesting the need to evaluate joint involvement with a specific activity index.References:[1]Cervera R et al. Medicine 1993[2]McElhone K. et al. Arthritis Rheum 2007.[3]Conti F et al. Lupus 2014Group (A)Group (B)pPH80,38 ± 21,4362,88 ± 23.28< 0.0001P82,36 ± 25.0862,30± 26.02< 0.0001PL83,04 ± 27.8270,58± 29.450.001IR84,49± 25.9965,36± 36.330.0005BO69,58 ± 28.4663,45± 28.950.129EH71,98 ± 24.6964,69± 23.050.0169F73,69 ± 24.2959,78±26.060.0004B78,14 ± 24.6156,28±30.14Disclosure of Interests:Francesco Natalucci: None declared, Fulvia Ceccarelli: None declared, enrica cipriano: None declared, Giulio Olivieri: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Simona Truglia: None declared, Francesca Miranda: None declared, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Guido Valesini: None declared

The role of infective agents in autoimmune diseases (ADs) development has been historically investigated, but in the last years has been strongly reconsidered due to the interest in the link between the microbiome and ADs. Together with the gut, the skin microbiome is characterized by the presence of several microorganisms, potentially influencing innate and adaptive immune response. S. aureus is one of the most important components of the skin microbiome that can colonize anterior nares without clinical manifestations. Data from the literature demonstrates a significantly higher prevalence of nasal colonization in ADs patients in comparison with healthy subjects, suggesting a possible role in terms of disease development and phenotypes. Thus, in the present narrative review we focused on the mechanisms by which S. aureus could influence the immune response and on its relationship with ADs, in particular granulomatosis with polyangiitis, rheumatoid arthritis, and systemic lupus erythematosus.

Background:The updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) underline the use of Mycophenolate Mofetil (MMF) in the treatment of different disease related manifestations (1). Several randomized controlled trials have demonstrated the efficacy of MMF in lupus nephritis (LN) patients but only case series and open-labelled trials have analyzed the use of this drug in other than LN features. Moreover, no data are available about the MMF retention rate in a real-life setting.Objectives:The present study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a large monocentric SLE cohort. Secondly, we investigated the influence of MMF in disease activity changes and chronic damage progression.Methods:We performed a longitudinal study including all the SLE patients (ACR 1997 criteria) starting MMF treatment in our Lupus Clinic. Data about indications, mean dosage, duration of treatment and reasons for drug withdrawal were registered. The DRR was estimated using the Kaplan–Meier method. Disease activity and chronic damage were assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SLICC Damage Index (SDI), respectively.Results:The present analysis included 162 SLE patients (M/F 22/140, median age at the disease diagnosis 25.5 years, IQR 13). At the beginning of MMF treatment, we registered a median age of 34 months (IQR 21) and a median disease duration of 72 months (IQR 123). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%), followed by neuropsychiatric involvement (10, 6.2%), and others disease related manifestations (12, 7.4%; in particular skin involvement, hematological features, myositis, vasculitis). MMF was administered at a mean daily dosage of 2.1±0.6 grams; no differences in dosage were found between the different indications (p=ns).At the longitudinal analysis, we registered a median treatment duration of 30 months (IQR 55). Figure 1 reported data about DRR: in particular, at 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (NLN) (60.5%; p=ns). Interestingly, the DRR at 60 months was higher in the subgroup of patients treated for joint involvement (75.4%), even without reaching a statistically significant difference. During the observation period, 92 patients (59.2%) discontinued MMF (median treatment duration at discontinuation 25 months, IQR 35). Interestingly, the main cause of withdrawal was the achievement of persistent remission, observed in 20 patients (21.7%), followed by loss of efficacy (19 patients, 20.5%), drug intolerance and pregnancy planning (17 patients for both reasons, 18,4%). Furthermore, our analysis confirmed MMF efficacy, as demonstrated by the significant reduction in SLEDAI-2k values after 4, 12 and 24 months of treatment (p< 0.0001 for all the time-points in comparison with baseline). In addition, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last observation: 0.93, IQR 1; p=ns).Conclusion:The evaluation of a large SLE cohort demonstrated a good retention rate for MMF. In particular, our results demonstrated that MMF is also a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it is able to control disease activity and to prevent the progression of chronic damage.References:[1]Fanouriakis A et al. Ann Rheum Dis. 2019 Jun;78(6):736-745.Disclosure of Interests:None declared

Background:Infective factors play a central role in autoimmune diseases pathogenesis. It is possible to speculate that the host genotype could interact with genetic background of infective agents. We previously evaluated a large SLE cohort, observing the association between theS. Aureus(SA) carriage status and presence of a more active disease in terms of autoantibodies positivity.Objectives:We evaluated epidemiological, molecular characterization, genetic diversity and evolution of SA isolated from SLE patients by means of phylogenetic analysis.Methods:Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate phylogenetic relationships and to assess significant clades in patients with persistent carriage status (nasal swab positive in two consecutive evaluation, performed 1 week apart). The first dataset was composed by seven SA tuf gene isolated from non-SLE individuals from different countries (downloaded from the GenBank database,https://www.ncbi.nlm.nih.gov/nucleotide/) and tuf gene SA collected from SLE patients enrolled in the present study.Results:We enrolled 118 patients (M/F 10/198; median age 45.5 years, IQR 13,2; median disease duration 120 months, IQR 144). Skin involvement is the most frequent disease manifestation (86 patients, 72.9%), followed by joint involvement (78 patients, 66.1%). Twenty-four patients (20.3%) were SA carriers (SA+), three of them resulted MRSA. SA+ patients showed a significantly higher prevalence of joint involvement (79.2%versus62.7%, P=0.01) and anti-dsDNA positivity (75.0%versus55.3%, P=0.004). Moreover, SA+ SLE showed a more active disease, in terms of SLEDAI-2k values [SA+: median 2 (IQR 3.75)versusSA-: median 0 (IQR 2), P=0.04). The phylogenetic analysis has been restricted on the 21 non-MRSA SA+ patients. The maximum likelihood phylogenetic tree of the first dataset revealed a statistically supported larger clade (A, N=17) and a smaller one (B, N=4; figure 1A). SLE patients located in the clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, PConclusion:The results of the present study confirmed the association between SA carriage status and disease activity, in terms of SLEDAI-2k values and anti-dsDNA positivity. The phylogenetic analysis ontufgene show a clustering ofSA+patients in two major clade (A and B). Interestingly thetufgenotype of clade A is significantly associated with a specific disease phenotype, characterized by joint involvement and positivity for anti-dsDNA. These findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.References:[1]Rigante et al. Int J Mol Sci. 2015;[2]Wertheim et al Lancet Infect Dis. 2005;[3]Conti et al Arthritis Res Ther 2016;[4]Tong et al Clin Microbiol Rev. 2015;[5]Rhee et al Infect Control Hosp Epidemiol. 2015Disclosure of Interests:Giulio Olivieri: None declared, Fulvia Ceccarelli: None declared, Alessandra Lo Presti: None declared, silvia angeletti: None declared, Carlo Perricone: None declared, Giancarlo Iaiani: None declared, Lucia De Florio: None declared, francesca antonelli: None declared, Luigino Amori: None declared, Cristina Garufi: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, cristiano Alessandri: None declared, Guido Valesini: None declared, Massimo Cicozzi: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

Background:The main outcomes in SLE patients management are represented by the remission achievement and chronic damage prevention. Even though activity and damage are intimately connected, to date indices including both these outcomes are not available.Objectives:In the present study, we aimed at assessing the application of a new index, the Lupus comprehensive disease control (LupusCDC), including disease activity and chronic damage progression.Methods:We performed a longitudinal analysis, including SLE patients according to ACR 1997 criteria, followed-up in the period between January 2014 and December 2018, and with at least one visit per year. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and three different remission levels were evaluated, as reported in Table 1 (1).Table 1.Remission levels considered in the study (1).Remission levelDefinitionComplete Remission(CR)No clinical and serological activity (SLEDAI-2K=0) in corticosteroid-free and immunosuppressant-free patients (antimalarials allowed)Clinical remission off-corticosteroids(ClR-GCoff)Serological activity with clinical quiescent disease according to SLEDAI-2K in corticosteroid-free patients (stable immunosuppressive therapy and antimalarials allowed)clinical remission on-corticosteroids(ClR-GCon)Clinical quiescent disease according to SLEDAI-2K in patients on prednisone 1–5 mg/day (stable immunosuppressants and antimalarials allowed)Chronic damage was registered according to SLICC damage index (SDI). All the patients were evaluated at baseline (T0) and every 12 months (T1, T2, T3, T4). At each time-point, we calculated the prevalence of LupusCDC, defined as remission achievement plus absence of chronic damage progression in the previous one year. We calculated this outcome including separately the different remission levels.Results:According with inclusion criteria, 172 SLE patients were evaluated in the present analysis [M/F 16/156, median age 49 years (IQR 16.7), median disease duration 180 months (IQR 156)]. At first assessment, we observed a mean±SD SDI value of 0.7±1.1. In details, 56 patients (32.5%) showed damage in at least one organ/system and the presence of damage was significantly associated with age (pIn figure 1A and 1B we reported the proportion of patients achieving the different levels of remission and LupusCDC, respectively. In particular, the LupusCDC definition including CR was the most frequently detected in all time-points evaluated (T1: 18.0%; T2: 31.9%; T3: 27.9%; T4: 24.4%), with a significant difference at T2 [LupusCDC(CR)versusLupusCDC(ClR-GCoff), p=0.0002; LupusCDC(CR)versusLupusCDC(ClR-GCon) p=0.0002)], T3 [LupusCDC(CR)versusLupusCDC(ClR-GCoff), p=0.03; LupusCDC(CR)versusLupusCDC(ClR-GCon) p=0.006], T4 [LupusCDC(CR)versusLupusCDC(ClR-GCon), p=0.002]. No significant differences were found when comparing the prevalence of different remission levels and the prevalence of LupusCDC including the corresponding remission.Conclusion:In the present analysis we proposed for the first time a new index including disease activity and chronic damage, in order to evaluate the proportion of SLE patients reaching a comprehensive disease control. We found that CR is most frequently associated with the absence of damage progression.References:[1]Zen M et al. Ann Rheum Dis 2017.Disclosure of Interests:Fulvia Ceccarelli: None declared, Giulio Olivieri: None declared, Lorenzo Dominici: None declared, Alessandra Ida Celia: None declared, enrica cipriano: None declared, Cristina Garufi: None declared, Silvia Mancuso: None declared, Francesco Natalucci: None declared, Valeria Orefice: None declared, Carlo Perricone: None declared, Carmelo Pirone: None declared, viviana antonella pacucci: None declared, Francesca Morello: None declared, Simona Truglia: None declared, Francesca Miranda: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease mainly affecting women of childbearing age. The interplay between genetic and environmental factors may contribute to disease pathogenesis1. At today, no robust data are available about the possible contribute of diet in SLE. Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor2.In vitrodose-dependent treatment with caffeine seems to down-regulate mRNA levels of key inflammation-related genes and similarly reduce levels of different pro-inflammatory cytokines3.Objectives:We evaluated the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokines levels.Methods:We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2k)4. Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided in four groups according to the daily caffeine intake: 376.6 mg/day (group 4)5. At the end of questionnaire filling, blood samples were collected from each patient to assess cytokines levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFN-γ, IFN-α and Blys.Results:We enrolled 89 SLE patients (F/M 87/2, median age 46 years, IQR 14; median disease duration 144 months, IQR 150). The median intake of caffeine was 195 mg/day (IQR 160.5). At the time of the enrollment, 8 patients (8.9%) referred a caffeine intake < 29.1 mg/day (group 1), 27 patients (30.3%) between 29.2 and 153.7 mg/day (group 2), 45 patients (51%) between 153.8 and 376.5 mg/day (group 3) and 9 patients (10.1%) >376.6 mg/day (group 4). A negative correlation between the levels of caffeine and disease activity, evaluated with SLEDAI-2K, was observed (p=0.01, r=-0.26). By comparing the four groups, a significant higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementemia and anti-dsDNA positivity was observed in patients with less intake of caffeine (figure 1 A-E). Furthermore, patients with less intake of caffeine showed a significant more frequent use of glucocorticoids [group 4: 22.2%,versusgroup 1 (50.0%, p=0.0001), group 2 (55.5%, p=0.0001), group 3 (40.0%, p=0.009)]. Moving on cytokines analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p=0.03, r=-0.2) (figure 2A); furthermore, patients with more caffeine intake showed significant lower levels of IFNα (p=0.02, figure 2B), IL-17 (p=0.01, figure 2C) and IL-6 (p=0.003, figure 2D).Conclusion:This is the first report demonstrating the impact of caffeine on SLE disease activity status, as demonstrated by the inverse correlation between its intake and both SLEDAI-2k values and cytokines levels. Moreover, in our cohort, patients with less caffeine consumption seems to have a more severe disease phenotype, especially in terms of renal and neuropsychiatric involvement. Our results seem to suggest a possible immunoregulatory dose-dependent effect of caffeine, through the modulation of serum cytokine levels, as already suggested byin vitroanalysis.References:[1]Kaul et alNat. Rev. Dis. Prim.2016; 2. Aronsen et alEurop Joul of Pharm2014; 3. Iris et alClin Immun.2018; 4. Gladman et al J Rheumatol. 2002; 5. Mikuls et alArth Rheum2002Disclosure of Interests:Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, cristiana barbati: None declared, Ramona Lucchetti: None declared, Giulio Olivieri: None declared, enrica cipriano: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

Growth hormone deficiency (GHD) is a condition associated with increased cardiovascular risk and insulin-resistance. Oxidative stress (OS) could be a mechanism underlying both these phenomena. In order to investigate plasma antioxidant defenses in such condition, we evaluated adults with GHD, compared with controls and metabolic syndrome patients (MetS), studying plasma total antioxidant capacity (TAC) and coenzyme Q10 (CoQ10, lipophilic antioxidant) levels, both in its oxidized and reduced forms, correlating this data with metabolic and hormonal pattern. In this case-control study, 51 GHD, 36 controls, and 35 MetS were enrolled. An evaluation of hormonal and metabolic parameters was performed. TAC was measured using the system metmyoglobin -H202 and the chromogen ABTS, whose radical form is spectroscopically revealed; latency time (LAG) in the appearance of ABTS● is proportional to antioxidant in sample. CoQ10 was assayed by electrochemical method. Despite HOMA index was higher in both GHD and MetS (2.2 ± 0.3 and 3.1 ± 0.3 vs. 1.2 ± 0.2 in controls), only in MetS we observed lower LAG levels (64.5 ± 3.1 s vs. 82.8 ± 5.8 in GHD and 80.6 ± 6.6 in controls), suggesting an increased consumption of antioxidants. LAG significantly correlated with uric acid only in MetS (r 2 = 0.65, p

Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases.

Background: Clinical management of chronic inflammation of prostate and seminal vesicles is very complex. Among the causes of recurrent chronic prostatitis (CP), a possible malabsorption, such as lactose intolerance, in turn related to small intestinal bacterial overgrowth (SIBO), should be considered. Methods: We have performed lactose and lactulose breath test (BT) in 42 patients with CP, in order to evaluate the prevalence of SIBO in this kind of patients and the concordance of the two tests. Results: A positive lactulose BT was present in 33/42 patients and in 73% (24/33) was associated to lactose malabsorption. Five patients had positive response after lactulose, while only 4 had both negative tests. Conclusions: Our data showed an association between lactose and lactulose BT positivity. They also indicated high prevalence of bacterial colonization of small bowel in patients with CP, possibly related to recurrence or chronicity of genitourinary tract inflammation. The research for these phenomena could be relevant in diagnostic route of infertile patients in whom slight gastro-enteric symptoms can be underestimated.