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To the Editor: The anti-dense fine speckled 70 (anti-DFS70) antibodies have recently become of interest because of their occurring in heterogeneous disorders including chronic inflammatory conditions, cancer, and systemic autoimmune rheumatic diseases (SARD), as well as in healthy individuals1,2,3. The frequency of anti-DFS70 antibodies in rheumatoid arthritis (RA) ranged from 0 to 2.6%4. There have been no studies examining the frequency of anti-DFS70 antibodies in spondyloarthritis (SpA) as a group, while only 1 study evaluated anti-DFS70 positivity in ankylosing spondylitis (AS)5. These autoantibodies could play protective or pathogenic roles, but the factors inducing their trigger are still uncertain6. In particular, the effect of biological treatments, extensively used in SARD management, on anti-DFS70 antibodies expression has not yet been investigated and thus represents an intriguing matter. Despite a vast amount of data supporting a role of anti–tumor necrosis factor-α (TNF-α) agents in the occurrence of immunogenicity7, no data were available about these drugs’ effect on the occurrence of anti-DFS70 antibodies. In addition, the induction of autoimmune phenomena such as the drug-induced lupus erythematosus … Address correspondence to Dr. V. Pafundi, Immunopathology Laboratory, San Carlo Hospital, Potito Petrone St., 85100 Potenza, Italy. E-mail: vito.pafundi{at}ospedalesancarlo.it

Background The University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA SCTC_GIT 2.0) questionnaire is a self-reported tool including 7-multi-item scales and measuring GI quality of life both in clinical trials and day-to-day clinic care of systemic sclerosis (SSc) patients (1). Scarce data are available on the correlation between patient reported GI symptoms and motility dysfunction as assessed by esophageal scintigraphy. Objectives To evaluate the UCLA SCTC_GIT 2.0 score in SSc patients undergoing esophageal scintigraphy and correlate their findings. Methods Data of SSc patients admitted to our clinic, undergoing esophageal scintigraphy, were reviewed. The score of UCLA SCTC_GIT 2.0, usually administered to all attending SSc patients, was calculated. Data were expressed as percentage (%) and mean ± standard error. Pearson’s test was used for Prism 7 correlation analysis. P Results Of all the SSc patients admitted to our clinic from 1stSept 2017 to 31st December 2018, twenty underwent esophageal scintigraphy. Seventeen were female, 4 with diffuse subset, mean age was 51 (± 3.4) years, disease duration of 6.8 (± 1.2 years) years. Twelve (60%) patients reported esophageal (reflux, dysphagia) symptoms, 5 (25%) stomach (early satiety, vomiting) and 9 (45%) intestinal (bloating, diarrhea, constipation) symptoms while 3 (15%) reported no symptoms. Mean ± SE scores of UCLA SCTC_GIT 2.0 items were: reflux 0.8 ± 0.2, distention 0.9 ± 0.2, fecal soiling 0.5 ± 0.2, diarrhea 0.5 ± 1, social 0.5 ± 0.1, emotional 0.5 ± 0.2, constipation 0.5 ± 0.1, and total UCLA SCTC_GIT 2.0 0.6 ± 0.1. Nine (45%) patients had no-mild, 4 (20%) moderate and 7 (35%) severe to very-severe reflux score. Esophageal scintigraphy showed hypomotility in 16 (80%) patients who had a higher UCLA SCTC_GIT 2.0 reflux score compared with the remaining 20% patients (1 ± 0.2 vs 0.3 ± 0.2). Fifteen/20 (75%) had an abnormal ( 0.05). Conclusion SSc patients with impaired esophageal scintigraphy findings have a higher GIT2 reflux score. The lack of correlation with UCLA SCTC_GIT 2.0 total score may be related to the composite nature of the score capturing overall GI disease aspects. The UCLA SCTC_GIT 2.0 is a complementary tool for objective measurement of esophageal involvement which can be easily administered in day-to-day clinical assessment. A larger number of SSc patients is needed to confirm these preliminary findings. Reference [1] Khanna D, Hays RD, Maranian P, et al. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum2009;61:1257-63. Disclosure of Interests Giuseppina Abignano: None declared, Gianna A. Mennillo: None declared, Antonio Carriero: None declared, Carmela Esposito: None declared, Angela Padula: None declared, Dinesh Khanna Shareholder of: Eicos Sciences, Inc, Grant/research support from: Bayer, BMS, Pfizer, Horizon, Consultant for: Actelion Acceleron, Arena, Bayer, BI, BMS, CSL Behring, Corbus, Cytori, GSK, Genentech/Roche, Galapagos, Employee of: Elcos Sciences, Inc, Salvatore D’Angelo: None declared

Background: Myositis can be a clinical feature of several rheumatic diseases. In inflammatory idiopathic myopathies (IIM), such as Dermatomyositis (DM), Polymyositis (PM), Antisynthetase syndrome (ASS), muscular lesions are immune-mediated and may associate with skin, aesophagus, lung, heart and joint involvement. The role of myositis specific antibodies (MSA) and myositis associated antibodies (MAA) in determining the clinical phenotype is still unclear. Anti-dense fine speckled antibodies (anti-DFS70ab) show a low frequency in DM and are generally associated with DM-specific autoantibodies Objectives: to characterize antibodies in IIM and myositis related to other rheumatic diseases and to correlate them to clinical features, cancer history and anti-DFS70ab presence. Methods: 37 patients with myositis (including IIM, overlap syndrome and myositis related to other rheumatic diseases) were evaluated. Anti-DFS70ab pattern was determined by indirect immunofluorescence on HEp-2000 cells. Detection of anti-DFS70ab specificity (truncated sequence of the DFS70 antigen (residues 349-435)), of MSA (MDA-5, TIF 1-γ, SAE1, SAE2, NXP-2, Jo-1, PL-7, PL-12, EJ, OJ, KS, ZO, HA, SRP, Mi-2,), of MAA (U1-RNP, SSaRo52/60, PM-Scl100/75, Ku) and of other Scleroderma associated antibodies (Scl-70, CENP-A, CENP-B, RNA Polymerase III, Th/to, Fibrillarin) were performed using immunoblotting assay. Clinical, serological and instrumental data were recorded. Results: 15 patients had a diagnosis of DM, 8 of PM, 3 of ASS, 5 of overlap syndrome (3 with Systemic Sclerosis (SSc), 1 with Sjogren Syndrome (SS), 1 with cryoglobulinemia), 6 of myositis related to other rheumatic disease (1 SSc, 1 Rheumatoid Arthritis, 2 Undifferentiated Connective Tissue Disease, 2 Systemic Lupus Erithematosus). In IIM, overall frequencies of MSA and MAA were 46.1% (12/26) and 38.4% (10/26), respectively, with concomitant expression in 5/26 cases. The 30.7% (8/26) of patients was negative for any type of antibodies. Mi-2 (4/15=26.6%), NXP-2 (3/15=20%) and SRP (2/15=15.3%) were detected in DM subset and were associated with typical skin lesions, muscle weakness, dysphagia and microvascular damage on capillaroscopy, while no interstitial lung disease, cardiac and articular involvement were recorded. Jo-1 was positive in 5/26 patients (2 PM, 2 ASS, 1 DM=19.2%) characterized by interstitial lung disease, arthritis, skin involvement and muscle weakness and by pulmonary hypertension when associated with TIF1- γ (1 DM=6.6%). Autoantibodies profile in overlap syndrome and myositis related to other rheumatic diseases was characterized by prevalence of MAA, more frequently PM-Scl100/75, RNP, Ku, SSaRo52/60. Only in 1 patient with an overlap syndrome SSc/PM HMGCR reactivity was detected. As far as cancer association, a positive history was found in 8.1% (3/37), related more frequently to Jo-1 and SSaRo52. Anti-DFS70ab were positive in 2/26 patients with IIM (7.6%; 1 DM and 1 PM) and in 1 with SSaRo60. No cases of anti-DFS70ab positivity was found in other subsets. Conclusion: Prevalence of MSA and MAA and their clinical correlations in our population are comparable to data reported in literature. Mi-2, NXP-2 and SRP can be considered markers of DM, while Jo-1 a predictor of lung involvement. Jo1/SSaRo52 positivity is reported in association with lung cancer, but to our knowledge no data are present about melanoma. Our preliminary data confirm that, not only in DM but also in PM, anti-DFS70ab were observed with a low frequency; however more studies are needed to establish the pathogenetic role of these antibodies. Disclosure of Interests: carmela esposito: None declared, Teresa Carbone: None declared, Antonio Carriero: None declared, valentina picerno: None declared, Maria Carmela Padula: None declared, Angela Padula Speakers bureau: Lilly Italia EMS, vito pafundi: None declared, Salvatore D’Angelo: None declared

Background: anti-DFS70 antibodies (anti-DFS70ab) were recently described as biomarkers clinically useful to discriminate Systemic Autoimmune Rheumatic Diseases (SARD) from non-SARD patients, especially if no concomitant SARD-specific autoantibodies were found. Several unanswered questions concerning the biological significance of this autoantibodies still remain. Objectives: to evaluate the prevalence of anti-DFS70ab in Rheumatoid Arthritis (RA) and Spondyloarthritis (SpA) patients and the influence of anti-TNF therapy on their development. Methods: sera from adult RA (n= 100) and SpA (n= 105) patients, included psoriatic arthritis, fulfilling ACR/EULAR 2010 and ASAS 2011 criteria, respectively, were studied for anti-DFS70ab as measured by IIF, then confirmed by immunoblotting. Medical history, demographic and clinical data were collected at enrolment. Results: the prevalence of anti-DFS70ab was 4.00% (4/100) in the RA and 4.76% (5/105) in SpA cohort. All anti-DFS70ab in RA patients were monospecific, while only 1 sample in SpA showed concomitant anti-centromere positivity. The findings for the anti-DFS70ab positivity revealed no statistical differences between the groups (p>0.05). In RA cohort, there were no differences between anti-DFS70ab positive and negative patients regarding the F/M ratio (F/M, 3/1 vs 84/12, p>0.05), mean age (50.2±12.4 vs 55.6±11.7 yrs, p>0.05) and disease duration (18.2±15.2 vs 14.0±9.9 yrs, p>0.05). In SpA group, no significant differences were found between patients with and without anti-DFS70ab in F/M ratio (3/2 vs 43/57, p>0.05) and regarding disease duration (18.8±7.7 vs 19.0±20 yrs, p>0.05) while the mean age of anti-DFS70ab patients was significantly higher than the negatives (66.8±10.4 vs 53.5±15.0 yrs, p Conclusion: based on our findings, detection of anti-DFS70ab reactivity cannot completely exclude the suspicion of SARD, especially for RA and SpA. In addition, the rate of anti-DFS70ab positivity resulted higher in RA and SpA patients than previously observed in a cohort of samples from outpatients clinics (2.1%) [1]. Immunogenicity of anti-TNF therapy has been also addressed in this study, showing that all detected anti-DFS70ab were induced by anti-TNF therapy. Further studies are needed to support these preliminary data. References [1] Carbone T. et al. Prevalence and serological profile of anti-DFS70 positive subjects from a routine ANA cohort. Scientific Report. 2019, In press. Disclosure of Interests: Teresa Carbone: None declared, carmela esposito: None declared, ornella mercuro: None declared, Antonio Carriero: None declared, valentina picerno: None declared, Maria Carmela Padula: None declared, Angela Padula Speakers bureau: Lilly Italia EMS, vito pafundi: None declared, Salvatore D’Angelo: None declared

Background: Anti-Dense Fine Speckled 70 (DFS70) antibodies are a common finding in clinical laboratory referrals. High prevalence of DFS70 autoantibodies in healthy population and usual negative association with Antinuclear Antibody (ANA)-associated autoimmune rheumatic diseases were reported. Objectives: The aim of this study was to evaluate the prevalence of anti-DFS70 antibodies in a routine diagnostic laboratory setting and their association with other circulating serum autoantibodies. Methods: Consecutive sera submitted for ANA screening were analyzed for anti-DFS70 antibodies by indirect immunofluorescence (IIF) (n=3175, 1030 men and 2145 women) then confirmed by Immunoblotting. IIF DFS70 positive adult patients were recruited previous written consent and tested for the following autoantibodies: anti-ENA, anti-dsDNA, -anti-TPO, anti-TG, anti-tTg, aCL, anti-PCA, AMA, ASMA, anti-LKM, anti-MPO, anti-PR3 and ASCAs. Results: The prevalence of anti-DFS70 antibodies was 1.7% (n= 55) in the whole population and 4.6% in the ANA-positive samples. Comparison between DFS70 IIF and Immunoblotting showed an excellent correlation between the two methods (R=0.99). Analysis of anti-DFS70 antibodies titers distribution revealed that 63% of the total cohort showed high titers (³1:640). Gender difference (female: male, 4:1) was observed in anti-DFS70 positive group and in anti-DFS70 negative/ANA positive group. The prevalence of anti-DFS70 positive female (2.1%, 45/2145) was statistically significant higher than males (1.0%, 10/1030) (p Conclusions: We found a prevalence of anti-DFS70 antibodies in adult sera from routine ANA cohort of 1.7%. The serological profile of DFS70-positive females required further investigations in order to define the presence of serum autoantibodies. Anti-DFS70 reactivity in male population may represent an exclusive biomarker predicting the absence of other autoantibodies. Acknowledgements: The authours would like to express their expecial appreciation and thanks to Prof. Ignazio Olivieri who died on July 28th, 2017. He was an example of strenght and tenacity with a contagious enthusiasm for a rigorous scientific research. Disclosure of Interest: None declared

Vasculitis is a heterogeneous group of disorders characterized by the presence of necrotic inflammatory phenomena and destruction of blood vessels. Vasculitis is classified as primary (idiopathic) or secondary to infections, connective tissue diseases and drugs but can also be considered as a paraneoplastic phenomenon. Evidence shows that the increasing use of biological agents results in a growing number of reports of autoimmune diseases induced by these therapies. An inflammatory articular chronic disease such as rheumatoid arthritis may be complicated by extra-articular manifestations, such as cutaneous or systemic vasculitis. Herewith, we describe the case of a great vessels arteritis in a patient affected by rheumatoid arthritis in therapy with an anti-TNF agent (etanercept).

Enteropathic arthritis (EA) is a spondyloarthritis (SpA) which occurs in patients with inflammatory bowel diseases (IBDs) and other gastrointestinal diseases. Diagnosis is generally established on the medical history and physical examination. It was, generally, made according to the European Spondyloarthropathy Study Group (ESSG) criteria. Rheumatic manifestations are the most frequent extraintestinal findings of IBD with a prevalence between 17% and 39%, and IBD is associated, less frequently, with other rheumatic disease such as rheumatoid arthritis, Sjogren syndrome, Takayasu arteritis, and fibromyalgia. Although the pathogenesis of EA has not been plainly clarified, the most popular theory supposes that joint inflammation occurs in genetically predisposed subjects with bacterial gut infections, provided an important evidence for a possible relationship between inflammation of the gut mucosa and arthritis. The management of patients with EA requires an active cooperation between the gastroenterologist and rheumatologist.

Osteoporosis (OP) is a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture. The prevalence of OP in the general population is very high as established in several studies, and OP represents one of the possible aspects of bone involvement in arthritis. In psoriatic arthritis this involvement is particularly complex because it affects not only mechanisms of bone loss but also of bone formation. We will discuss these aspects and the available epidemiological data.

Background Pharmacogenetic testing for drug-metabolizing enzymes is not yet widely used in clinical practice. Methods In an attempt to facilitate the application of this procedure, we have compared two real-time PCR-based methods, the TaqMan and the LightCycler for the pharmacogenetic evaluation of CYP2C9*2/*3 polymorphisms. Results and conclusion Both procedures are suitable for pharmacogenetic studies. The TaqMan procedure was less expensive in terms of cost per sample, but the TaqMan apparatus is more expensive than the LightCycler apparatus.