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Maria Maddalena Angioni,1 Alberto Floris,1 Ignazio Cangemi,1 Mattia Congia,1 Elisabetta Chessa,1 Sandro Orrù,2 Matteo Piga,1 Alberto Cauli1 1Rheumatology Unit, Department of Medical Sciences and Public Health, University of Cagliari, University Clinic AOU, Cagliari, 09042, Italy; 2Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, 09042, ItalyCorrespondence: Maria Maddalena AngioniRheumatology Unit, Department of Medical Sciences and Public Health, University of Cagliari, University Clinic AOU Cagliari, S.S. 554, Bivio per Sestu, Monserrato, Cagliari, 09042, ItalyTel +39 07051093340Email m.maddalena.angioni@gmail.comIntroduction: Psoriatic Arthritis (PsA) is a multifactorial disease, where the relative burden of genetic, epigenetic and environmental factors in clinical course and damage accrual is not yet definitively clarified. In clinical practice, there is a real need for useful candidate biomarkers in PsA diagnosis and disease progression, by exploring its underlying transcriptomic and epigenomic mechanisms. This work aims to profile the transcriptome in monozygotic (MZ) twins with psoriatic arthritis (PsA) highly concordant for clinical presentation, but discordant for the radiographic outcomes’ severity.Methods: We describe i) the clinical case of two MZ twins; ii) their comparative gene expression profiling (HTA 2.0 Affymetrix) and iii) signal pathways and pathophysiological processes in which differentially expressed genes are involved (in silico analysis by the IPA software, QIAGEN).Results: One hundred sixty-three transcripts and 36 coding genes (28 up and 8 down) were differentially expressed between twins, and in the brother with the most erosive form, the transcriptomic profiling highlights the overexpression of genes known to be involved in immunomodulatory processes and on a broad spectrum of PsA manifestations.Discussion: Twins’ clinical cases are still a gold mine in medical research: twin brothers are ideal experimental models in estimating the relative importance of genetic versus nongenetic components as determinants of complex phenotypes, non-Mendelian and multifactorial diseases as PsA.Keywords: psoriatic arthritis, gene expression profiling, diseases in twin, genetic, environment–gene interaction, joint erosions

Alberto Floris, Matteo Piga, Silvia Pinna, Maria Maddalena Angioni, Mattia Congia, Piero Mascia, Elisabetta Chessa, Ignazio Cangemi, Alessandro Mathieu, Alberto Cauli Rheumatology Unit, AOU University Clinic and University of Cagliari, Cagliari, ItalyCorrespondence: Matteo PigaRheumatology Unit, University Clinic AOU of Cagliari, SS 554, Monserrato, CA 09042, ItalyTel +390706754069Fax +39070513157Email matteopiga@unica.itPurpose: 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 Behçet’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 Behçet’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.Keywords: circulating endothelial cells, CECs, endothelial progenitor cells, EPCs, Behçet’s syndrome

Elisabetta Chessa, Matteo Piga, Alberto Floris, Alessandro Mathieu, Alberto Cauli Rheumatology Unit, University Clinic AOU of Cagliari, Cagliari, Italy Abstract: 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. Keywords: systemic lupus erythematosus, neuropsychiatric lupus, rituximab, demyelinating syndrome, brain MRI

Alberto Cauli, Matteo Piga, Alberto Floris, Alessandro Mathieu Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Monserrato, Cagliari, Italy Abstract: TH17 is a lymphocyte subset, which is characterized by its polarization to secrete interleukin (IL)-17. IL-23 is the pivotal mediator responsible for TH17 differentiation and the IL-23/IL-17 axis has been strongly implicated in the pathogenesis of several immune mediated diseases, in particular chronic arthritis and skin psoriasis. This review will summarize the basic immunology and the new monoclonal antibodies, which antagonize this pathway allowing a new therapeutic approach. Keywords: TH17, IL-17, IL-23, psoriasis, psoriatic arthritis, ankylosing spondylitis

Alberto Cauli, Giovanni Porru, Matteo Piga, Alessandra Vacca, Grazia Dessole, Alessandro MathieuRheumatology Unit, Department of Medical Sciences, Policlinico of University of Cagliari, Monserrato, ItalyAbstract: Psoriatic arthritis (PsA) is a frequent chronic inflammatory disease characterized by joint and skin involvement, and by typical extra-articular manifestations. Although the pathogenesis of PsA is still under investigation, the available evidence suggests the importance of the patient's genetic background, microbial or environmental triggers, and an imbalance in the adaptive and acquired immune system, resulting in the production of inflammatory mediators. New therapeutic approaches have been proposed, among them the use of modulators of intracellular signals and gene transcription such as PDE4-inhibiting compounds, which are able to modulate the activity of transcription factors such as CREB and NF-κB and therefore the synthesis of inflammatory mediators, resulting in immunoregulation. This paper summarizes the mechanism of action of apremilast, a PDE4 inhibitor, and the clinical data available on its clinical efficacy and safety profile in the treatment of PsA patients.Keywords: psoriatic arthritis, apremilast, therapy