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Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

OBJECTIVE To compare the effect of achievement and maintenance of Lupus Low Disease Activity State (LLDAS) and clinical remission (CR) in preventing early damage accrual in patients with systemic lupus erythematosus (SLE). METHODS In a monocentric cohort of 116 newly diagnosed SLE patients, LLDAS and CR achievement at 6 months (T1) after treatment initiation and their maintenance over the next 12 months were assessed. Early damage was recorded after 18 months of follow-up (T2) using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Univariate and multivariate analyses were performed to evaluate the association of LLDAS and CR with early damage. RESULTS LLDAS was significantly more attained than CR both at T1 (42.2% versus 21.6% of patients; P < 0.001) and T2 (46.6% versus 31.9%; P = 0.022). The overlap rate between persistent LLDAS and persistent CR was 41.7% (n = 15). On multivariate analysis, achievement of CR (odds ratio [OR] 0.07 [95% confidence interval (95% CI) 0.01-0.59], P = 0.015) and LLDAS (OR 0.25 [95% CI 0.06-0.99], P = 0.049) at T1 were independently associated with lower accrual of early damage. Patients who achieved LLDAS (including CR) at T1 and steadily persisted in this condition until T2 developed significantly less damage compared to those who failed to maintain it during the T1-T2 interval (P = 0.003), those who achieved it later than T1 (P < 0.001), or those who had never been in this condition (P < 0.001). CONCLUSION Although CR is recommended as the primary treatment target in SLE, LLDAS represents a valid alternative in the early stage of SLE management. LLDAS and CR maintenance should be targeted to prevent damage.

© Copyright Clinical and Experimental Rheumatology 2022., Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods: We conducted a multicentre, international, retrospective cohort study. Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.

The identification of anti-NXP2 antibodies is considered a serological marker of dermatomyositis (DM), with calcinosis, severe myositis and, in some reports, with cancer. Historically, these associations with anti-NXP2 antibodies have been detected by immunoprecipitation (IP), but in the last few years commercial immunoblotting assays have been released. The aim of this collaborative project was to analyse the clinical features associated to anti-NXP2 antibodies, both with commercial line blot (LB) and IP. Myositis-specific and myositis-associated autoantibodies were detected in single centres by commercial line blot (LB); available sera were evaluated in a single centre by protein and RNA immunoprecipitation (IP), and IP-Western blot. Sixty patients anti-NXP2+ (NXP2+) positive by LB were compared with 211 patients anti-NXP2 negative with idiopathic inflammatory myositis (IIM). NXP2+ showed a younger age at IIM onset (p = 0.0014), more frequent diagnosis of dermatomyositis (p = 0.026) and inclusion-body myositis (p = 0.009), and lower rate of anti-synthetase syndrome (p

Purpose To explore the potential role of circulating endothelial cells (CECs) and their progenitors (EPCs) as biomarkers of disease activity and damage accrual in patients with Behcet's syndrome (BS), by using a standardised and reliable flow cytometry protocol. Patients and methods CECs and EPCs were assessed in 32 BS patients and 11 gender/age/smoking habits matched healthy controls (HC). They were identified by flow cytometry as alive/nucleated/CD45-negative/CD34-bright/CD146-positive and alive/nucleated/CD45-negative/CD34-bright/CD309-positive events, respectively. In BS patients, demographic and clinical features, including disease activity (assessed by Behcet's disease current disease activity form, BDCAF) and irreversible damage accrual (by the vasculitis damage index, VDI) were recorded. Uni- and multivariate analysis were performed to compare the CECs and EPCs concentrations in BS vs HC and to identify potential associations with demographic or clinical features. Results The CECs concentration was significantly higher in the BS patients than HCs [median (IQR) 15.0 (7.5-23.0) vs 6.0 (2.0-13.0) CECs/mL, p=0.024]. In BS patients, no significant associations were found between CECs and demographic features, present and past clinical manifestations, BDCAF score and ongoing treatment. A significant association was observed between CECs and organ damage, as assessed by the VDI (rho 0.356, p=0.045). Higher levels of CECs were especially associated with vascular damage [median (IQR) 23.0 (14.0-47.0) vs 13.0 (6.0-19.0) CECs/mL, p=0.011], including arterial aneurysm and stenosis, complicated venous thrombosis, cerebrovascular accident. The concentration of EPCs did not significantly differ between the BS and HC [median 26.5 (13.0-46.0) vs 19.0 (4.0-42.0) EPCs/mL, p=0.316] and no significant associations were observed between their levels and any clinical characteristic. Conclusion Our study suggests that the CECs concentration is significantly higher in BS than healthy subjects, and it mainly correlates with vascular damage. A longitudinal extension of the present study on a wider cohort would be useful to validate the potential role of CECs as a marker or, hopefully, predictor of vascular damage in BS.

Objectives: The recent introduction of direct-acting antiviral agents (DAAs) which can eliminate Hepatitis C virus (HCV) had revolutionized the treatment of HCV infections also in a complex clinical setting such as the patients with rheumatoid arthritis (RA). HCV elimination is also opportune due to the availability of more efficient immunosuppressive drugs, whose effect on the course of HCV infection is largely unknown. Methods: Consensus process was endorsed by the Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) to review the available evidence and produce practical, hospital-wide recommendations. The consensus panel consisted of 18 infectious diseases consultants, 20 rheumatologists and one clinical epidemiologist, who used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. Results: A core-set of statements about management of patients with RA and infection by HCV have been developed to help clinicians in their clinical practice. Conclusions: A screening for HCV should be performed in all RA patients and it is mandatory before starting an immunosuppressive therapy. Finally, a DAA treatment should be considered in all HCV-infected patients.Significance and Innovations HCV antibodies should be investigated at the time of diagnosis of RA and, in any case, before starting immunosuppressive therapy with disease-modifying antirheumatic drugs (DMARDs). HCV eradication with DAA should be attempted as soon as possible, depending on patient conditions allowing a continuous oral treatment lasting 8–12 weeks Conventional and biological DMARDs are allowed in patients with HCV infection, but they should be used cautiously in presence of advanced liver disease.

Identifying predictors of inadequate response to methotrexate (MTX) in rheumatoid arthritis (RA) is key to move from a “trial and error” to a “personalized medicine” treatment approach where patients less likely to adequately respond to MTX monotherapy could start combination therapy at an earlier stage. This study aimed to identify potential predictors of inadequate response to MTX in RA patients naïve to disease modifying anti-rheumatic drugs. Data from a real-life cohort of newly diagnosed RA patients starting MTX (baseline, T0) as first-line therapy were analyzed. Outcomes, assessed after 6 months (T1), were defined as failure to achieve a disease activity score 28 (DAS28) low disease activity (LDA) or a good/moderate response to MTX, according to the European League Against Rheumatism (EULAR) response criteria. Logistic regression was used to assess the associations between baseline variables and the study outcomes. Overall, 294 patients (60.5% females, median age 54.5 years) with a median disease duration of 7.9 months were recruited. At T1, 47.3% of subjects failed to achieve LDA, and 29.3% did not have any EULAR-response. In multivariate analysis, significant associations were observed between no LDA and current smoking (adjusted odds ratio [adjOR] 1.79, P = .037), female gender (adjOR 1.68, P = .048), and higher DAS28 (adjOR 1.31, P = .013); and between no EULAR-response and current smoking (adjOR: 2.04, P = .019), age (adjOR: 0.72 per 10-years increases, P = .001), and higher erythrocyte sedimentation rate (adjOR: 0.49; P = .020). By contrast, there were no associations between past smoker status and study outcomes. In summary, in our real-life cohort of disease modifying anti-rheumatic drug naïve RA patients, current smoking habit independently predicts inadequate response to MTX. This, together with other independent predictors of response to treatment identified in our study, might assist with personalized monitoring in RA patients. Further studies are required to investigate whether smoking quitting strategies enhance the therapeutic response to MTX.

Background The aim of this study was to evaluate the prevalence and clinical significance of Anti-neuronal antibodies (AnAb) in a cohort of neuropsychiatric (NP) Systemic Lupus Erythematosus (SLE) patients. Methods Overall, 28 SLE patients (age 45.6 ± 14.4 years) with inflammatory neuropsychiatric syndromes, classified according to existing criteria (1, 2) were enrolled and serum samples were collected before starting treatment for the specific NP event; 41 consecutive SLE patients (44.2 ± 14.2 years) without NP involvement, 22 Multiple Sclerosis patients (37.9 ± 11.0 years) and 82 healthy subjects (44.8 ± 15.0 years) served as controls. Search for AnAb was performed by tissue-based immunohistochemistry assays (IHC) on male Sprague Dawley rat’s brain sections and confirmed by cell-based immunocytochemistry assays on SH-SY5Y (human neuroblastoma) cell cultures. The association between serum positivity for AnAb by IHC and a large panel of data (demographic, serologic, SLEDAI, conventional brain MRI, treatment) was investigated by univariate analysis. Multivariate models were fitted with covariates with p Results AnAb were detected in 23 (82.1%) NPSLE patients and in 16 (39.0%) SLE patients without NP involvement resulting in 82% specificity (95%CI 71%-90%) and 61% sensitivity (95%CI 48%-72%) in differentiating NPSLE from SLE without NP involvement. None of the sera from MS patients (0%) and healthy subjects (0%) showed AnAb. Serum AnAb by IHC were independently associated with NPSLE (p Conclusion AnAb are significantly more frequent in patients with NPSLE than SLE. Further studies are needed to identify the unknown neuronal antigens targeted by AnAb in SLE patients.

Background/Purpose To compare the independent effect of achievement and maintenance of lupus low disease activity state (LLDAS) and clinical remission (CR) in preventing early damage accrual in the early stage of systemic lupus erythematosus (SLE) management. Methods In a monocentric inception cohort of 116 newly diagnosed SLE patients, LLDAS and CR achievement at 6 months (T1) after treatment initiation and their maintenance over the next 12 (T2) months were assessed. Early damage was assessed (T2) using the SLICC/damage index. Uni- and multivariate analysis were performed to evaluate the association of LLDAS and CR with early damage. Results LLDAS achievement was significantly more frequent than CR both at T1 (42.2% vs. 21.6%, p The overlap between persistent LLDAS and persistent CR between T1 and T2 was observed in 41.7% of cases. On multivariate analysis, the achievement of CR (OR 0.1, 95%CI 0.01–0.59, p=0.015) and LLDAS without CR (OR 0.2; 95%CI 0.06–0.99, p=0.049) at T1, as well as younger age at onset (OR 0.95, 95%CI 0.91–0.98, p=0.004), were negatively associated with early damage. Patients who achieved LLDAS at T1 and steadily persisted in this condition until T2 developed significantly less damage compared to those who failed to maintain it during the T1-T2 interval (p=0.003), those who achieved it later than T1 (p Conclusions Although CR is recommended as the primary treatment target in SLE, LLDAS may represent a valid alternative in the early stage of SLE management. LLDAS and CR maintenance should be targeted to prevent damage.

Objective To investigate risk factors for damage development in a prospective inception cohort of early diagnosed SLE patients. Methods The Early Lupus Project recruited an inception cohort of patients within 12 months of SLE classification (1997 ACR criteria). At enrolment and every 6 months thereafter, the SLICC/ACR Damage Index was recorded. The contribution of baseline and time-varying covariates to the development of damage, defined as any SLICC/ACR Damage Index increase from 0 to ≥1, was assessed using univariate analysis. Forward-backward Cox regression models were fitted with covariates with P Results Overall, 230 patients with a mean (s.d.) age of 36.5 (14.4) years were eligible for this study; the mean number of visits per patient was 5.3 (2.7). There were 51 (22.2%) patients with SLICC/ACR Damage Index ≥1 after 12 months, 59 (25.6%) after 24 months and 67 (29.1%) after 36 months. Dyslipidaemia [P = 0.001; hazard ratio (HR) 2.9; 95% CI 1.5, 5.6], older age (P = 0.001; HR 3.0; 95% CI 1.6, 5.5), number of organs/systems involved (P = 0.002; HR 1.4; 95% CI 1.1, 1.8) and cardiorespiratory involvement (P = 0.041; HR 1.9; 95% CI 1.0, 3.7) were independently associated with an increased risk of developing damage. Risk profiles for damage development differed for glucocorticoid-related and -unrelated damage. HCQ use (P = 0.005; HR 0.4; 95% CI 0.2, 0.8) reduced the risk of glucocorticoid-unrelated damage. Conclusion We identified risk factors of damage development, but little effect of glucocorticoids, in this early SLE cohort. Addressing modifiable risk factors from the time of SLE diagnosis might improve patient outcomes.

Objective To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. Methods In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54-59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009). Conclusion In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

Demyelinating syndrome secondary to systemic lupus erythematosus (DS-SLE) is a rare encephalomyelitis burden with a high risk of disability and death. We report on a 49-year-old Caucasian woman with systemic lupus erythematosus (SLE) complicated by severe cognitive dysfunction, brainstem disease, cranial nerve palsies, weakness and numbness in limbs and multiple discrete magnetic resonance imaging (MRI) areas of damage within the white matter of semioval centers, temporal lobe, external capsule, claustrum, subinsular regions and midbrain. She also had multiple mononeuritis diagnosed through sensory and motor nerve conduction study. She was diagnosed with severe DS-SLE prominently involving the brain and was treated with 500 mg methylprednisolone (PRE) pulses for 3 consecutive days, followed by one single pulse of 500 mg cyclophosphamide, and 1 g rituximab, which was then repeated 14 days later. PRE 25 mg/day, rapidly tapered to 7.5 mg/day in 6 months, and mycophenolate mofetil 1 g/day were prescribed as maintenance therapy. She had progressive and sustained improvement in neurological symptoms with almost complete resolution of brain MRI lesions after 1 year. B-cell depleting therapy could be considered as a possible alternative to standard of care in the management of severe inflammatory neuropsychiatric SLE but it should be associated with a conventional immunosuppressant as maintenance treatment to reduce the risk of flare and reduce corticosteroids dose.

Objective To describe features of demyelinating syndrome (DS) in systemic lupus erythematosus (SLE). Methods A systematic review using a combination of Mesh terms in PubMed and a retrospective analysis of 343 adult patients with SLE were carried out to identify patients with DS. Retrieved cases were classified as affected with DS according to 1999 ACR nomenclature and attributed to SLE by applying the 2015 algorithm. DS defined according to the clinical but not temporal 1999 ACR criteria was classified as clinically isolated syndrome (CIS). Results Estimated prevalence of DS (including CIS) in the SLE cohort was 1.3% and incidence rate was 1.5 cases per 1000 patient-years. Overall, 100 cases from literature review and 4 from SLE cohort were identified and are presented as a whole: 49 (47.1%) were classified as neuromyelitis optica spectrum disorders (NMOSD), 29 (27.9%) as CIS, 14 (13.5%) as NMO, 7 (6.7%) as DS prominently involving the brainstem and 5 (4.8%) as DS prominently involving the brain. DS was the SLE onset manifestation in 41 (39.4%) patients. Longitudinally extensive transverse myelitis was the most frequent manifestations being present in 73 (70.2%) patients (37 NMOSD, 21 CIS, 14 NMO, 1 DSB). Methylprednisolone (79.8%) and cyclophosphamide (55.8%) pulses, but also plasma-exchange (16.3%) and rituximab (7.6%) in relapsing-refractory cases, were mostly prescribed. Complete recovery rate ranged between 62% in CIS to 7% in NMO. Conclusion DS in SLE is rare (1%) and encompasses different subtypes including CIS. Timely diagnosis and early treatment are recommended to minimize complications.

The human leukocyte antigen HLA-B27 is a strong risk factor for Ankylosing Spondylitis (AS), an immune-mediated disorder affecting axial skeleton and sacroiliac joints. Additionally, evidence exists sustaining a strong protective role for HLA-B27 in viral infections. These two aspects could stem from common molecular mechanisms. Recently, we have found that the HLA-B*2705 presents an EBV epitope (pEBNA3A-RPPIFIRRL), lacking the canonical B27 binding motif but known as immunodominant in the HLA-B7 context of presentation. Notably, 69% of B*2705 carriers, mostly patients with AS, possess B*2705-restricted, pEBNA3A-specific CD8+ T cells. Contrarily, the non-AS-associated B*2709 allele, distinguished from the B*2705 by the single His116Asp polymorphism, is unable to display this peptide and, accordingly, B*2709 healthy subjects do not unleash specific T cell responses. Herein, we investigated whether the reactivity towards pEBNA3A could be a side effect of the recognition of the natural longer peptide (pKEBNA3A) having the classical B27 consensus (KRPPIFIRRL). The stimulation of PBMC from B*2705 positive patients with AS in parallel with both pEBNA3A and pKEBNA3A did not allow to reach an unambiguous conclusion since the differences in the magnitude of the response measured as percentage of IFN&gamma, producing CD8+ T cells were not statistically significant. Interestingly, computational analysis suggested a structural shift of pEBNA3A as well as of pKEBNA3A into the B27 grooves, leaving the A pocket partially unfilled. To our knowledge this is the first report of a viral peptide: HLA-B27 complex recognized by TCRs in spite of a partially empty groove. This implies a rethinking of the actual B27 immunopeptidome crucial for viral immune-surveillance and autoimmunity.

Background Remission is an important goal of therapy in psoriatic arthritis (PsA), but data on molecular players of clinical remission and effective disease inactivation are scarce. Gene expression profiling analysis could be useful to elucidate the pathogenic mechanisms of diseases, and differential gene expression analysis between diverse disease conditions produces gene signatures characteristic of the state or disease being studied. Objectives Our aim was to compare the transcriptional profiles of patients with clinically active versus inactive (remission state) PsA (peripheral joint subset), and healthy controls (HCs). Methods From a cohort of around 300 patients affected by PsA according to CASPAR criteria, we first selected 20 patients (peripheral arthritis subset) with active disease state (without biologic treatment ongoing) (A) and 20 patients with >1-year remission induced by TNFα antagonism (R), as assessed by DAPSA > 14, and DAPSA ≤ 4 scores respectively, and from 20 HCs matching for age and gender ratio. Both PsA groups were not on corticosteroid treatment. RNA from peripheral blood was extracted and, following quality analysis by Agilent Bioanalyzer, each condition has been profiled using RNAs pools in biological duplicates by distinct Affymetrix Human GeneChip HTA 2.0, for a total of 6 arrays. Data analysis was performed using the commercial software Partek Genomics Suite, V 6.6. To identify a transcript as differentially expressed, a value of fold change 1.5 and p-value 0.05 has been set. Results The Venn diagram shows all comparative groups (A vs R, A vs HC, R vs HC) with their relative amount of transcripts differentially expressed, generated using abovementioned parameters, and the relationship between sets (fig1, panel A). Using the list of transcripts differentially expressed in at least one of the aforementioned comparison, a hierarchical clustering was carried out to highlight the intra-condition expression profile. We have identified (arbitrarily) 4 clusters of transcripts with analogous transcriptional profile and to each of them a color code has been assigned (Heatmap in Fig1, panel B). For these clusters and for all lists of transcripts differentially expressed founded by our comparative study, we carried out the Gene Set Enrichment Analysis by Gene Ontology (GO), in order to identify how molecular functions, cellular components or biological processes occurs more frequently than expected in a reference list of transcripts. Conclusion Observing the amount of differentially expressed transcripts, is evident that while active disease state (A) has a clear-cut different profile, the drug-induced remission (R) is more similar with HCs condition. However, in the hierarchical clustering this trend of similarity does not appear in all clusters of transcripts, as shown particularly in the red, orange and green clusters. Again, the Gene Set Enrichment Analysis Score showed us that mRNA transcripts dysregulated in the R condition vs HCs, are involved in several biological processes related to immune system, development, response to stimulus, localization and others. Our next step will be to validate, by Real Time PCR in a large cohort of patients, the most interesting dysregulated genes covering biological functions eventually sustaining subclinical activity in PsA. Disclosure of Interests None declared

Background Belimumab is the unique biologic therapy available for patients with SLE. Objectives To investigate effectiveness and safety of belimumab in SLE patients in clinical practice. Methods 458 active SLE patients (ACR criteria) from 24 Italian Centers, mean±SD age 43.5±11.3 years; mean±SD disease duration 12.3±8.7 years, were treated with belimumab (10 mg/kg day 0, 14, 28 and then every 28 days), as add-on therapy. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24H proteinuria, CLASI, PGA, Fatigue (VAS 0-10) were recorded at baseline and every 6 months. Flares were defined according to SFI. Response was evaluated according to SRI-4. Statistics were performed by pairs T-test, chi-square test and multiple logistic regression (SPSS, version 22.0). Results Mean±SD follow-up was 21.2±15.3 months (range 3-60). Most common features treated with belimumab were articular in 67%, mucocutaneous in 55%, and renal in 17% of cases. Improvement of clinical and serological variables, including daily prednisone dosage, was observed (Table). SRI-4 is summarized in the Figure. At the end of follow-up 293 patients (66%) were still on belimumab. Most common cause of discontinuation were inadequate response (36%), AEs (31%), and pregnancy (8%). Mean number of flare during belimumab treatment compared with the corresponding period before belimumab initiation decreased (p 9,998 infusions were analyzed. 784 AEs were observed in 330 patients, SAEs were 43 in 36 patients. No severe infusion reactions were observed; 16 patients had infective SAEs, and 22 non infective SAEs. Conclusion We confirmed the effectiveness, the steroid sparing effect and good safety profile of belimumab in our cohort. Disclosure of Interests Luca Iaccarino: None declared, Francesca Saccon: None declared, Alessandro Mathieu: None declared, Matteo Piga: None declared, Angela Ceribelli: None declared, Carlo Selmi Grant/research support from: Abbvie, Janssen, MSD, Novartis, Pfizer, Consultant for: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Speakers bureau: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Paolo Cardinaletti: None declared, Armando Gabrielli: None declared, Andrea Di Matteo: None declared, Rossella De Angelis: None declared, Paola Faggioli: None declared, Antonella Laria: None declared, Micaela Fredi: None declared, Francesca Regola: None declared, Laura Andreoli: None declared, Giulia Pazzola: None declared, Carlo Salvarani: None declared, Francesco Puppo: None declared, Simone Negrini: None declared, Marcella Prete: None declared, Vito Racanelli: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Maria Gerosa: None declared, Tania Ubiali: None declared, Enrica Bozzolo: None declared, Valentina Canti: None declared, Fabrizio Conti: None declared, Fulvia Ceccarelli: None declared, Elena Bartoloni Bocci: None declared, Roberto Gerli: None declared, Antonio Lobasso: None declared, Amato De Paulis: None declared, Ginevra De Marchi: None declared, Salvatore De Vita Grant/research support from: Roche, Pfizer, Abbvie, Novartis, BMS, MSD, Celgene, Janssen, Consultant for: Roche, Alessandra Bortoluzzi: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, Francesco Benvenuti: None declared, Margherita Zen: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Chiara Tani: None declared, Maurizio Rossini: None declared, Giovanni Orsolini Speakers bureau: Grunenthal, Mariele Gatto: None declared, Salvatore Scarpato: None declared, Enrico Brunetta: None declared, Aurora Zumbo: None declared, Gabriele Valentini: None declared, SERENA FASANO: None declared, Giacomo Emmi: None declared, Maria Letizia Urban: None declared, Giacomo Tanti: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Andrea Doria: None declared

Background Disease activity evaluation is mandatory according to the OMERACT Core Set of Domains for Behcet’s Syndrome (BS). Poor data are available on Patient (PtGA) and physician (PGA) global assessment of disease activity in BS. Objectives To assess PtGA performance in patients with BS and how different disease manifestations influence the patient and physician’s perception of disease activity. Methods A multicenter cross-sectional cohort of consecutive BS patients was enrolled. Disease activity was evaluated by PtGA, PGA and the Behcet’s disease current activity form (BDCAF). PtGA and PGA were assessed trough a single question (“How active was BS during the last week?”) in a 10-cm visual analogic scale. Health related quality of life (HRQoL) perception was evaluated by the Physical Component Summary (PCS) and the Mental Component summary (MCS) of the SF36v2 questionnaire. Correlation between PtGA, PGA, BDCAF and between them and SF36v2 component summaries was assessed trough the Spearman’s correlation coefficient (rho). Two separated multiple regression models were built to measure the independent effect (β regression) of each active clinical manifestation on PtGA and PGA. Results Overall, 226 BS patients from 5 Mediterranean Countries were enrolled. Out of them, 111 (49.1%) were males and the median (IQR) age and disease duration were 46.9 (35.6-55.2) and 11.7 (5.9-20.8) years, respectively. The median (IQR) value of PtGA, PGA and BDCAF were 2.0 (0.3-5.0), 1.0 (0.0-3.0) and 3.0 (0.0-5.0), respectively. PtGA significantly correlated (Figure) with both PGA (rho 0.759. p 0.001) and MCS (rho -451. p > 0.001). Conclusion PtGA seems to be a valid outcome measure in BS and should be considered as a separate outcome measure or better be included in composite index for overall disease activity evaluation. Disclosure of Interests Alberto Floris: None declared, Matteo Piga: None declared, Gerard Espinosa: None declared, Nikolaos Kougkas: None declared, Andrea Lo Monaco: None declared, Giuseppe Lopalco Speakers bureau: SOBI, BMS, Ida Orlando: None declared, Vittorio Pirani: None declared, Ernestina Santos: None declared, Luisa Serpa Pinto: None declared, George Bertsias: None declared, Luca Cantarini: None declared, Alberto Cauli: None declared, Ricard Cervera: None declared, Joao Correia: None declared, Marcello Govoni: None declared, Florenzo Iannone Consultant for: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Speakers bureau: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Ana Martins da Silva: None declared, Piergiorgio Neri: None declared, Carlos Vasconcelos: None declared, Alessandro Mathieu: None declared

Background: Remission is an important goal of therapy in rheumatoid arthritis (RA), but data on molecular players of clinical remission and effective disease inactivation are scarce. Gene expression profiling analysis is useful to elucidate the pathogenic mechanisms of diseases, and differential gene expression analysis between diverse disease conditions produces gene signatures characteristic of the state or disease being studied. Objectives: Our aim was to compare the transcriptional profiles of patients with clinically active versus inactive (remission state) RA, and healthy controls (HCs). Methods: From a cohort of around 1000 patients affected by RA according to ACR-EULAR 2010 criteria, we first selected 20 patients with active disease state (without biologic treatment ongoing) (A) and 20 patients with >1-year remission induced by TNFα antagonism (Etanercept) (R), as assessed by DAS28(PCR) scores, and from 20 HCs matching for age and gender ratio. Both RA groups were not on corticosteroid treatment. RNA from peripheral blood was extracted and, following quality analysis by Agilent Bioanalyzer, each condition has been profiled using RNAs pools in biological duplicates by distinct Affymetrix Human GeneChip HTA 2.0, for a total of 6 arrays. Data analysis was performed using the commercial software Partek Genomics Suite, V 6.6. To identify a transcript as differentially expressed, a value of fold change 1.5 and p-value 0.05 has been set. Results: The Venn diagram shows all comparative groups (A vs R, A vs HC, R vs HC) with their relative amount of transcripts differentially expressed, generated using abovementioned parameters, and the relationship between sets (fig1, panel A). Using the list of transcripts differentially expressed in at least one of the aforementioned comparison, a hierarchical clustering was carried out to view the intra-condition expression profile. Here, we have identified (arbitrarily) 4 clusters of transcripts with analogous transcriptional profile and to each of them a color code has been assigned (Heatmap in Fig1, panel B). For these clusters and for all lists of transcripts differentially expressed founded by our comparative study, we carried out the Gene Set Enrichment Analysis by Gene Ontology (GO), in order to identify how molecular functions, cellular components or biological processes occurs more frequently than expected in a reference list of transcripts. Conclusion: Considering the amount of differentially expressed transcripts and the hierarchical clustering analysis, is evident that the drug-induced remission (R) is more similar with HCs condition, while active disease state (A) has a different profile; however “similar” profile does not mean “identical”. In fact, the Gene Set Enrichment Analysis Score showed us that mRNA transcripts dysregulated in the R condition vs HCs, are involved in several biological processes regarding the immune system, response to stimulus, biological regulation, locomotion and others. Our next step will be to validate, by Real Time PCR in a large cohort of patients, the most interesting dysregulated genes covering biological functions eventually sustaining disease activity. Disclosure of Interests: None declared

Background Methotrexate (MTX) is the gold standard as first line treatment in rheumatoid arthritis (RA). Identifying predictors of response to MTX should be crucial in the view of a personalized therapy. Objectives To identify prevalence and potential clinical baseline predictors of inadequate response (IR) to MTX in RA patients naive to disease modifying anti-rheumatic drugs (DMARDs)*. Methods Data of 233 consecutive RA patients (according to ACR/EULAR 2010 criteria) naive to traditional and biologic DMARDs, attending the AOU University Clinic, Rheumatology Unit, Monserrato (Cagliari), Italy, were analyzed. Table 1 shows baseline demographic, clinical and serological characteristics of the cohort. Patients failing to reach low disease activity state (DAS 28 > 3.2) at 6 months (T1) since the beginning of MTX (T0) or patients undergoing therapeutic modification for persistently high disease activity (switch or addition of other traditional or biological DMARDs) before T1 were considered as IR. By univariate analysis, demographic, clinical and serological factors recorded at T0 were evaluated as potential predictors of IR at T1. Afterwards, factors with p Results At T1, 104 patients (44.6%) were classified as IR to MTX. In univariate analysis, factors significantly associated with IR were: female gender (69.2% vs. 54.3%; p=0.02), condition of ”current smoker” (22.1% vs. 10.9%; p=0.012), ESR [median (IQR): 30.0 (19.0-48.0) vs. 40.0 (25-62); p=0.035] and DAS28 (mean ± standard deviation: 5.5 ± 1.1 vs. 5.2 ± 1.3; p=0.037). High-titre positivity for RF and/or ACPA (57.3% vs. 45.9%; p=0.095) and high cumulative steroids dose [852 mg (300-1200) vs. 691 mg (0-150); p=0.071] were numerically higher in IR. In multivariate analysis, the ”current smoker” condition was confirmed as the only independent factor associated with IR to MTX after 6 months of treatment (OR: 2.333, 95% CI: 1.132-4.805; p=0.022). No significant association between ex-smoker status and IR to MTX was demonstrated. This result was confirmed even after stratification of ex-smokers over the time since smoking stop. Finally, for both current smokers and ex-smokers, the duration of exposure to cigarette smoking did not show any significant association with IR. Conclusion In this RA cohort, the condition of ”current smoker” was the only predictor of IR to MTX. This observation, together with the lack of association between previous smoking habit and IR to MTX, further prompt to recommend cessation of cigarette smoking in patients with RA who begin treatment with MTX. Acknowledgement This study was supported by an unconditioned Research grant from Pfizer Inc. Disclosure of Interests None declared

Objective: Neonatal Lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro and anti-La/SSB autoantibodies to the fetus. The rarity of this condition requires the establishment of multidisciplinary registries in order to improve our knowledge.Method: Inclusion criteria in this retrospective study were the maternal confirmed positivity for anti-SSA/Ro and/or anti-SSB/La antibodies, and the presence of II or III degree congenital heart block (CHB) in utero or neonatal period (up to 27 days after birth).Result: Eighty-nine cases of CHB were observed in 85 women with 88 pregnancies that occurred between 1969 and 2017. CHB was mostly detected in utero (84 cases, 94.2%), while five cases were observed in the neonatal period. A permanent pacemaker was implanted in 51 of 73 children born alive (69.8), whereas global mortality rate was 25.8% (23 cases): 16 in utero, five perinatal, and two during childhood. By univariate analysis, factors associated with fetal death were pleural effusion (p = 0.005, OR > 100; CI 95% 2.88->100 and hydrops (p = 0.003, OR = 14.09; CI 95% 2.01–122). Fluorinated steroids (FS) were administered in 71.4% pregnancies, and its use was not associated with better survival. Some centers treated all cases with fluorinated steroids and some centers did not treat any case. CHB was initially incomplete in 24 fetuses, and of them five cases of II degree block reverted to a lower degree block after treatments. Recurrence rate in subsequent pregnancies was 17.6% (3 out of 17). A prophylactic treatment was introduced in 10 of these 16 subsequent (58.8%) pregnancies, mostly with FS or high dose intravenous immunoglobulins.Conclusion: This is the first report from the Italian Registry of neonatal lupus/CHB. The live birth rate was nearly 80%, with nearly two thirds of the children requiring the implantation of a pacemaker. The management of fetuses diagnosed with CHB was heterogeneous across Italian Centers. The registry at present is mainly rheumatological, but involvement of pediatric cardiologists and gynecologists is planned.

Objectives HLA-B27 and the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 genes are predisposing factors for AS. A single nucleotide polymorphism (SNP) in the ERAP2 promoter (rs75862629) coordinates the transcription of both ERAP genes. We investigated whether this SNP associates with AS and whether it affects the expression of the two major HLA-B27 alleles present in Sardinia, the AS-associated B*2705 and the non-AS-associated B*2709. Methods Four SNPs in the ERAP region were genotyped in HLA-B*2705-positive patients with AS (n = 145), B27-positive healthy subjects (n = 126) and B27-negative controls (n = 250) and the allele and haplotype frequencies were derived. The expression of ERAP1 and ERAP2 mRNAs in 36 HLA-B27-positive B lymphoblastoid cell lines was measured by quantitative PCR. An electrophoretic mobility shift assay was performed to search for a nuclear factor binding the DNA sequence encompassing rs75862629. The expression of HLA-B27 molecules related to the SNP at rs75862629 was determined by flow cytometry. Results The minor allele G at rs75862629 was found significantly increased in B27 healthy individuals, both B*2705 and B*2709, compared with B*2705-positive patients with AS and B27-negative controls. The electrophoretic mobility shift assay indicated the lack of binding of a transcription factor as the cause of the observed reduction in the ERAP2 concomitant with a higher ERAP1 expression. Of note, this occurs with a different cell surface expression of the HLA-B*2705 and HLA-B*2709 molecules. Conclusion SNP rs75862629, by modulating simultaneously the expression of ERAP1 and ERAP2, provides protection from AS in HLA-B27-positive subjects in Sardinia. This has a functional impact on HLA-B27 expression and likely on disease onset.

Patients with Systemic Lupus Erythematosus (SLE) may experience flare of disease activity. The aim of this study was to assess incidence, clinical features and predictors of flares, focusing on the relationship with serially assessed anti-double stranded DNA antibodies (anti-dsDNA) serum levels by Farr assay and pre-emptive therapeutic approaches of flares, through the analysis of a monocentric cohort of SLE patients and a literature review. Clinical and laboratory data of 120 out of 334 SLE patients, fulfilling inclusion criteria for enrolment and followed up between 1997 and 2012, were retrospectively collected. For the purposes of the study, a flare was defined as any new SLE manifestation or worsening of a pre-existing manifestation resulting in change of therapy. A review of the literature was performed searching for articles published between 1980 and 2015. Over a median (IQR) follow-up of 5.9 (3.0-8.9) years, 87 flares were recorded in 59 (49%) patients. The estimated incidence rate was 0.11 flare per patient-year, at the low-end of values reported in literature (0.19-1.76 patient-year). In our cohort, fluctuating anti-dsDNA serum levels were associated with flare development whereas precautionary change of therapy in presence of increased anti-dsDNA levels >50% was effective in preventing flares (p

The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for genetic association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been found to be associated with AS. The highly homogenous genetic structure of the Sardinian population has favored the search of relevant variants for disease-association studies. Moreover, malaria, once endemic in the island, has been shown to have contributed to shape the native population genome affecting the relative allele frequency of relevant genes. In Sardinia, the prevalence of HLA-B*2709, which differs from the strongly AS-associated B*2705 prototype for one amino acid (His/Asp116) in the F pocket of the peptide binding groove, is around 20% of all HLA-B27 alleles. We have previously hypothesized that malaria could have contributed to the establishment of this allele in Sardinia. Based on our recent findings, in this perspective article we speculate that the Endoplasmic Reticulum Amino Peptidases, ERAP1 and 2, associated with AS and involved in antigen presentation, underwent co-selection by malaria. These genes, besides shaping the immunopeptidome of HLA-class I molecules, have other biological functions that could also be involved in the immunosurveillance against malaria.

Background Anti-MDA5 antibodies are a known set of antibodies observed mainly in dermatomyositis, typically associated with cutaneous involvement, presence and often rapid progression (RP) of interstitial lung disease (ILD) and amyopathic muscle involvement. Despite the increased attention, described cohorts involves only a limited number of cases Objectives to define clinical characteristics of a large cohort of anti-MDA5 antibodies positive patients Methods Retrospective assessment of anti-MDA5 positive patients from centres referring to our group Results 82 anti-MDA5 positive cases (56 females) were collected. In median: onset age was 44 Y (IQR 22.57), diagnostic delay 4 Mo (IQR 1–10), follow-up 13 Mo (IQR 3–43). Fifty-three patients had ILD, that was RP in 24 cases (15 at ILD onset, 9 after ILD onset). Fifthteen ILD patients were admitted in Intensive Care Unit (ICU): 4 were treated with Extracorporeal-Membrane-Oxygenation, 7 with mechanical-invasive and 2 with mechanical-non-invasive ventilation. Forthy-nine patients had muscle involvement (39 symptomatic), 42 arthritis, 54 cutaneous involvement, 9 history of malignancy. Twelve patients died (ILD=7, ILD and sepsis=3, neoplasia=1, not specified=1), 7 of those in ICU Conclusions In our cohort, ILD was the most frequent finding. A RP of ILD was common, occurring also in ILD with symptomatic/chronic onset. The low rate of survival in ICU raised the problem of follow up and early treatment of ILD. In our cohort arthritis was common and muscle involvement mainly symptomatic. Finally, the high percentage of observed malignancies suggests a careful neoplastic screening and follow up Reference [1] Labrador-Horrillo M, et al. J Immunol Res2014;2014:290797. Disclosure of Interest None declared

Background Behcet's disease (BD) is a polygenic immune-mediated disorder characterized by a close association with the HLA-B*51 allele. The HLA region has a strong linkage disequilibrium (LD) and carries several genetic variants (e.g. MIC-A, TNF-α genes) identified as associated to BD because of their LD with HLA-B*51. In fact, the HLA-B*51 is inherited as part of extended HLA haplotypes which are well preserved in patients with BD. Sardinian population is highly differentiated from other Mediterranean populations because of a distinctive genetic structure with very highly preserved HLA haplotypes. Patients and methods In order to identify other genes of susceptibility to BD within the HLA region we investigated the distribution of human Allograft Inflammatory Factor-1 (AIF-1) gene variants among BD patients and healthy controls from Sardinia. Six (rs2736182; rs2259571; rs2269475; rs2857597; rs13195276; rs4711274) AIF-1 single nucleotide polymorphisms (SNPs) and related extended haplotypes have been investigated as well as their LD within the HLA region and with HLA-B*51. Overall, 64 BD patients, 43 HLA-B*51 positive healthy controls (HC) and 70 random HC were enrolled in the study. Results HLA-B*51 was the only allele with significantly higher frequency (pc = 0.0021) in BD patients (40.6%) than in HC (9.8%). The rs2259571T AIF-1 variant had a significantly reduced phenotypic, but not allelic frequency in BD patients (72.1%; pc = 0.014) compared to healthy population (91.3%). That was likely due to the LD between HLA-B*51 and rs2259571G (pc = 9E-5), even though the rs2259571G distribution did not significantly differ between BD patients and HC. Conclusion No significant difference in distribution of AIF-1 SNPs haplotypes was observed between BD patients and HC and between HLA-B*51 positive BD patients and HLA-B*51 positive HC. Taken together, these results suggest that AIF-1 gene is not associated with susceptibility to BD in Sardinia.

Objective.Physician’s global assessment (PGA) of disease activity is a major determinant of therapeutic decision making. This study assesses the reliability of the PGA, measured by means of 0–100 mm visual analog scale (VAS), and the additional use of separate VAS scales for musculoskeletal (PhysMSK) and dermatologic (PhysSk) manifestations in patients with psoriatic arthritis (PsA).Methods.Sixteen centers from 8 countries enrolled 319 consecutive patients with PsA. PGA, PhysMSK, and PhysSk evaluation forms were administered at enrollment (W0) and after 1 week (W1). Detailed clinical data regarding musculoskeletal (MSK) manifestations, as well as dermatological assessment, were recorded.Results.Comparison of W0 and W1 scores showed no significant variation (intraclass correlation coefficients were PGA 0.87, PhysMSK 0.86, PhysSk 0.78), demonstrating the reliability of the instrument. PGA scores were dependent on PhysMSK and PhysSk (p < 0.0001) with a major effect of the MSK component (B = 0.69) compared to skin (B = 0.32). PhysMSK was correlated with the number of swollen joints, tender joints, and presence of dactylitis (p < 0.0001). PhysSk scores were correlated with the extent of skin psoriasis and by face, buttocks or intergluteal, and feet involvement (p < 0.0001). Finally, physician and patient assessments were compared showing frequent mismatch and a scattered dot plot: PGA versus patient’s global assessment (r = 0.36), PhysMSK versus patient MSK (r = 0.39), and PhysSk versus patient skin (r = 0.49).Conclusion.PGA assessed by means of VAS is a reliable tool to assess MSK and dermatological disease activity. PGA may diverge from patient self-evaluation. Because MSK and skin/nail disease activity may diverge, it is suggested that both PhysMSK and PhysSk are assessed.

Polymyalgia rheumatica (PMR) is an elderly onset syndrome characterised by aching and stiffness in the shoulders and the pelvic girdle associated to increased levels of acute phase reactants and rapid response to glucocorticoids.1 Although the cause of PMR remains unknown, most of the evidence suggest a multifactorial aetiology inducing an immunomediated pathogenesis.1 2 According to the ‘immunological continuum model’ proposed by McGonagle in 2006, all immune-mediated diseases can be conceptualised as predominantly autoinflammatory, predominantly autoimmune or mixed, on the basis of the relative contributions of innate and adaptive immune responses.3 Autoinflammatory diseases (AIDs) are characterised by tissue inflammation mainly due to aberrant activation of innate immune system without autoantibodies production and autoreactive T lymphocyte activation. In contrast, autoimmune diseases (ADs) are typically depicted by an abnormal activation of the adaptive immune system.4 However, the emerging understanding of the close linkage between innate and adaptive immunity led to consider the rare monogenic AIDs and ADs as the two opposite ends into a continuum of immune-mediated disorders, where middle entities are recognised (figure 1).3 Figure 1 Simplified classification of immune-mediated disease by McGonagle and McDermott.3 In the view of this background, we tried to envisage the most suitable place for PMR into the spectrum of the autoinflammatory/autoimmune disorders by reviewing and interpreting current evidence. Clear indication for a prevalent autoinflammatory background of PMR is related to the disease onset and course. Actually, starting of symptoms is generally over a few days or overnight in PMR,1 as well as in inflammatory periodic-recurring occurrence of AIDs,5 but in contrast to classic polygenic ADs where a subacute onset is frequently recorded (figure 2A).6 Further, after low-dose glucocorticoid therapy initiation, patients with PMR experience a rapid improvement of symptoms, generally within 24–72 hours, and more than 40% of them achieve …

The aim of this study was to evaluate systemic sclerosis (SSc) hospitalizations through a retrospective population-based study analyzing administrative data during 2001–2012 in Sardinia, an Italian region with universal Health System coverage. Data on hospital discharge records with ICD-9-CM code for SSc (710.1) were obtained from the Department of Health and Hygiene. Two-tailed Cochran–Armitage test for trend was applied to analyze the annual trend for primary and non-primary discharge diagnoses. SSc prevalence was also estimated. This study included 4981 hospitalizations in 736 patients (84.8 % women). Hospitalizations with SSc as primary diagnosis were 3631 (72.9 %). Their annual number significantly increased during study period, from 143 in 2001 to 390 in 2012. Annual trend analysis revealed statistically significant increase in number and percentage of interstitial lung disease (p

Objective The objective of this paper is to evaluate hospital admissions in systemic lupus erythematosus (SLE) patients through a retrospective population-based study analyzing hospitalization data during 2001–2012 in Sardinia, an Italian region with universal health system coverage. Methods Data on the hospital discharge records with the ICD-9-CM code for SLE (710.0) were obtained from the Department of Health and Hygiene and analyzed, mostly focusing on primary and non-primary diagnosis and Diagnosis-Related Group (DRG) code. In order to establish the significance of the annual trend for number and type of primary and non-primary discharge diagnosis, the two-tailed Cochran-Armitage test for trend was applied. In order to estimate SLE prevalence, data from administrative database and medical records were assembled. Results This study included 6222 hospitalizations in 1675 patients (87% women). Hospitalizations with SLE as primary diagnosis were 3782 (58.0%) and significantly decreased during the study period. The annual number of renal, hematologic and neuropsychiatric disorders as non-primary diagnosis associated with SLE remained constant; however, their percentage increased ( p Conclusions While overall hospitalizations for SLE patients declined, those for cerebrovascular accident, acute coronary syndrome and chronic renal failure as underlying primary diagnosis increased during the study period.

Background The aim was to assess the attainability and outcome of the lupus low disease activity state (LLDAS) in the early stages of systemic lupus erythematosus (SLE). Methods LLDAS prevalence was evaluated at 6 (T1) and 18 (T2) months after diagnosis and treatment initiation (T0) in a monocentric cohort of 107 (median disease duration 9.7 months) prospectively followed Caucasian patients with SLE. Reasons for failure to achieve LLDAS were also investigated. Multivariate models were built to identify factors associated with lack of LLDAS achievement and to investigate the relationship between LLDAS and Systemic Lupus International Collaboration Clinics (SLICC)/Damage Index (SDI) accrual. Results There were 47 (43.9%) patients in LLDAS at T1 and 48 (44.9%) at T2. The most frequent unmet LLDAS criterion was prednisolone dose >7.5 mg/day (83% of patients with no LLDAS at T1). Disease manifestations with the lowest remission rate during follow up were increased anti-double-stranded DNA (persistently present in 85.7% and 67.5% of cases at T1 and T2, respectively), low serum complement fractions (73.2% and 66.3%) and renal abnormalities (46.4% and 28.6%). Renal involvement at T0 was significantly associated with failure to achieve LLDAS both at T1 (OR 7.8, 95% CI 1.4–43.4; p = 0.019) and T2 (OR 3.9, 95% CI 1.4–10.6; p = 0.008). Presence of any organ damage (SDI ≥1) at T2 was significantly associated with lack of LLDAS at T1 (OR 5.0, 95% CI 1.5–16.6; p = 0.009) and older age at diagnosis (OR 1.05 per year, 95% CI 1.01–1.09; p = 0.020). Conclusion LLDAS is a promising treatment target in the early stages of SLE, being attainable and negatively associated with damage accrual, but it fit poorly to patients with renal involvement.