roberta priori

@policlinicoumberto1.it

UOC Reumatologia
Azienda Ospedaliera Universitaria Policlinico Umberto I



           

https://researchid.co/priorir

RESEARCH INTERESTS

rheumatology, Autoimmunity, autoinflammation, sjogren's syndrome

198

Scopus Publications

Scopus Publications

  • Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome
    Alejandra Flores-Chávez, Pilar Brito-Zerón, Wan-Fai Ng, Antónia Szántó, Astrid Rasmussen, Roberta Priori, Chiara Baldini, Berkan Armagan, Burcugül Özkiziltaş, Sonja Praprotnik,et al.
    Clinical and Experimental Rheumatology
    OBJECTIVES To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. METHODS For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. RESULTS After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. CONCLUSIONS Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.

  • Exposure to air pollution as an environmental determinant of how Sjögren’s disease is expressed at diagnosis


  • The pathogenic role of metabolism in Sjögren's syndrome
    Serena Colafrancesco, Edoardo Simoncelli, Roberta Priori, and Michele Bombardieri
    Clinical and Experimental Rheumatology
    The link between immune cell function and cell metabolic reprogramming is currently known under the term "immunometabolism". Similarly to the Warburg's effect described in cancer cells, in activated immune cells an up-regulation of specific metabolic pathways has been described and seems to be pathogenic in different inflammatory conditions.Sjӧgren's syndrome (SS) is a systemic autoimmune disease that affects the exocrine glands and is characterised by a progressive loss of secretory function. Despite the increasing amount of evidence on the ability of metabolism in regulating cell behaviour in inflammatory or tumoral conditions, the field of metabolism in SS is still for the most part unexplored.The aim of this review is to summarise currently available studies evaluating cell metabolism in SS with a particular focus on the possible pathogenic role of metabolic changes in immune and non-immune cells in this condition.


  • Expert consensus on the treatment of patients with adult-onset still's disease with the goal of achieving an early and long-term remission
    Roberto Giacomelli, Roberto Caporali, Francesco Ciccia, Serena Colafrancesco, Lorenzo Dagna, Marcello Govoni, Florenzo Iannone, Pietro Leccese, Carlomaurizio Montecucco, Giovanni Pappagallo,et al.
    Elsevier BV

  • Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients
    Sara Monti, Alessandra Milanesi, Catherine Klersy, Alessandro Tomelleri, Lorenzo Dagna, Corrado Campochiaro, Nicola Farina, Francesco Muratore, Elena Galli, Chiara Marvisi,et al.
    BMJ
    BackgroundImmune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce.MethodsPatients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65–79 and ≥80 years old.ResultsThe study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23–91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65–79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p&lt;0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients &gt;65 years old had 2–3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age &gt;65, cranial and systemic symptoms as independent risk factors.ConclusionsThe highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

  • Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study
    Pilar Brito-Zerón, Alejandra Flores-Chávez, Ildiko Fanny Horváth, Astrid Rasmussen, Xiaomei Li, Peter Olsson, Arjan Vissink, Roberta Priori, Berkan Armagan, Gabriela Hernandez-Molina,et al.
    Elsevier BV

  • Involvement of Substance P (SP) and Its Related NK1 Receptor in Primary Sjögren’s Syndrome (pSS) Pathogenesis
    Pamela Rosso, Elena Fico, Serena Colafrancesco, Mario Giuseppe Bellizzi, Roberta Priori, Bruna Cerbelli, Martina Leopizzi, Carla Giordano, Antonio Greco, Paola Tirassa,et al.
    MDPI AG
    Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target.

  • PCSK3 Overexpression in Sjögren’s Syndrome Patients May Be Regulated by rs4932178 SNP in Its Promoter Region and Correlates with IFN-γ Gene Expression
    Andrea Latini, Giada De Benedittis, Serena Colafrancesco, Carlo Perricone, Giuseppe Novelli, Lucia Novelli, Roberta Priori, Cinzia Ciccacci, and Paola Borgiani
    MDPI AG
    Background: The PCSK3 gene encodes for the protease enzyme Furin, which promotes proteolytic maturation of important regulators of the immune response, and also enhances the secretion of interferon-γ (IFN). Several studies have suggested its possible involvement in the pathogenesis of chronic inflammatory diseases. Methods: We investigated the PCSK3 gene expression level in peripheral blood mononuclear cells isolated from Sjögren’s Syndrome (SS) patients and healthy controls and we evaluated a possible correlation with IFN-γ gene expression. Moreover, we also explored the variability of two PCSK3 genetic polymorphisms (rs4932178 and rs4702) to evaluate a possible association between these polymorphisms and the expression levels of this gene. Results: We observed, by RT-qPCR, that the PCSK3 expression level was significantly higher in SS patients compared to the controls (p = 0.028), and we confirmed a positive correlation between PCSK3 and IFN-γ expression levels (p &lt; 0.001). Moreover, we reported that the variant homozygous genotype of rs4932178 SNP is associated with a higher expression of the PCSK3 gene (p = 0.038) and with the SS susceptibility (p = 0.016). Conclusions: Our data suggest that Furin could play a role in SS development, also promoting IFN-γ secretion.

  • Multicentre case-control study evaluating the safety of anti-SARS-CoV-2 vaccines in a cohort of patients with systemic vasculitis
    Edoardo Simoncelli, Edoardo Conticini, Serena Colafrancesco, Angelica Gattamelata, Francesca Romana Spinelli, Cristina Garufi, Simona Truglia, Silvia Grazzini, Federico Giardina, Raffaella Izzo,et al.
    Clinical and Experimental Rheumatology
    OBJECTIVES Data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis (SV), are limited. The aim of this study was to evaluate the occurrence of a disease flare and the appearance of adverse events (AEs) following administration of anti-SARS-CoV-2 vaccine in a multicentre cohort of patients with SV. METHODS Patients with SV and healthy controls (HC) from two different Italian rheumatology centres were asked to complete a questionnaire assessing disease flares occurrence, defined as new onset of clinical manifestations related to vasculitis needing an implementation of therapy, and local/systemic AEs appearance following anti SARS-CoV-2 vaccination. RESULTS 107 patients with SV (57 ANCA-associated) and 107 HC were enrolled. A disease flare occurred in only one patient (0.93%) with microscopic polyangiitis after the first dose of an mRNA vaccine. After both the first and the second vaccine dose administration, no significant differences in AEs between patients with SV and HC were observed; no serious AEs were reported as well. CONCLUSIONS These data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.

  • Effectiveness of non-medical switch from adalimumab bio-originator to SB5 biosimilar and from ABP501 adalimumab biosimilar to SB5 biosimilar in patients with chronic inflammatory arthropathies: a monocentric observational study
    Rossana Scrivo, Chiara Castellani, Silvia Mancuso, Giorgio Sciarra, Federico Giardina, Giulia Bevignani, Fulvia Ceccarelli, Francesca Romana Spinelli, Cristiano Alessandri, Manuela Di Franco,et al.
    Clinical and Experimental Rheumatology
    OBJECTIVES The use of biosimilars is constantly growing, prompting healthcare payers to encourage the switch to these drugs which are less expensive than the reference bio-originator. While switching from a bio-originator to a biosimilar is supported by increasing evidence, data on the switch between different biosimilars of the same reference product are scant. Our study aimed to evaluate the effectiveness of the non-medical switch both between adalimumab (ADA) bio-originator and SB5 biosimilar and between two different ADA biosimilars in patients with inflammatory chronic arthritis. METHODS We observed adult patients with a diagnosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) treated with ADA bio-originator or ABP501 ADA biosimilar (Amgevita) who switched to SB5 ADA biosimilar (Imraldi) for administrative/economic reasons. Patients were followed up for 4 months. RESULTS One hundred and ten patients [33 RA, 40 PsA, 37 axSpA; F:M= 49:61; median age 56 years (25th-75th percentile 48-66)] switched from ADA bio-originator to SB5. After 4 months (T4), we observed a significant reduction of patients in remission/low disease activity (baseline 92.7% vs. T4 80.9%; p=0.009), with a risk of moderate-high disease activity significantly higher after the switch [RR 2.6 (95% IC 1.2 to 5.7), p=0.01]. However, no differences were found in DAS28-CRP, DAPSA, ASDAS-CRP, and BASDAI, while patients with RA and PsA experienced a worsening in the patient global assessment-VAS (p=0.04 and p=0.02, respectively), and in patients with PsA a worsening in HAQ was also observed (p=0.03). Forty patients switched from ABP501 biosimilar to SB5 [12 with RA, 25 with PsA, and 3 with axSpA; F:M=24:16; median age 56 years (25th-75th percentile 44-66)]. After 4 months, no differences in DAS28-CRP and DAPSA nor in the percentage of patients in remission/low disease activity were found compared to baseline. Likewise, no differences were found in patient-reported outcomes (PROs). CONCLUSIONS Our results provide a reassuring profile of effectiveness when switching from ADA originator to one of its biosimilars and between two different biosimilars. However, the worse outcome in PROs in patients initially treated with the bio-originator addresses the attention to a possible nocebo response, which should encourage comprehensive communication with patients.

  • Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies
    Gabriela Hernández-Molina, Belchin Kostov, Pilar Brito-Zerón, Arjan Vissink, Thomas Mandl, Anneline C Hinrichs, Luca Quartuccio, Chiara Baldini, Raphaele Seror, Antonia Szántó,et al.
    Oxford University Press (OUP)
    Abstract Objective To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.

  • Multiple Cutaneous Manifestations in ANCA-Positive Eosinophilic Granulomatosis with Polyangiitis before and after Biologic Therapy: Clinical and Histopathologic Characterization of a Paradigmatic Case
    Giorgia Carnicelli, Alvise Sernicola, Vito Gomes, Giulia Cundari, Stefania Trasarti, Roberta Priori, and Teresa Grieco
    MDPI AG
    Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare immune-mediated vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Having systemic and possibly severe involvement, a prompt recognition of its clinical features is crucial to achieve favorable patient outcomes. Although cutaneous manifestations represent key elements, these still remain poorly characterized. We report a case of ANCA-positive EGPA presenting with palpable purpura, livedo reticularis, and pemphigoid-like lesions that was successfully treated with glucocorticoid therapy and rituximab. This report portrays the evolution of cutaneous lesions in ANCA-positive EGPA and demonstrates how dermatologic signs may represent indicators of active disease, allowing for timely diagnosis and for the monitoring of disease activity during treatment.

  • Safety and efficacy of SARS-CoV-2 vaccination in 1237 patients with primary Sjögren syndrome
    Nevsun Inanc, Belchin Kostov, Roberta Priori, Alejandra Flores-Chavez, Francesco Carubbi, Antónia Szántó, Valeria Valim, Hendrika Bootsma, Sonja Praprotnik, Virginia Fernandes Moça Trevisani,et al.
    Clinical and Experimental Rheumatology

  • Cultural adaptation and preliminary validation of the Qualisex questionnaire for its use in patients with Sjögren's syndrome and fibromyalgia in Italy
    Roberta Priori, Federico Giardina, Chiara Gioia, Cristina Iannuccelli, Martina Villa, Angelica Gattamelata, Fabrizio Conti, Manuela Di Franco, and Giuseppe Curcio
    Clinical and Experimental Rheumatology

  • Alteration of Mitochondrial DNA Copy Number and Increased Expression Levels of Mitochondrial Dynamics-Related Genes in Sjögren’s Syndrome
    Giada De Benedittis, Andrea Latini, Serena Colafrancesco, Roberta Priori, Carlo Perricone, Lucia Novelli, Paola Borgiani, and Cinzia Ciccacci
    MDPI AG
    Sjögren’s syndrome (SS) is a chronic autoimmune multifactorial disease characterized by inflammation and lymphocytic infiltration of the exocrine glands. Several studies have highlighted the involvement of oxidative stress in this pathology, suggesting that it could induce mitochondrial dysfunctions. Mitochondria could have a role in inflammatory and immune processes. Since the mitochondrial DNA (mtDNA) copy number could change in response to physiological or environmental stimuli, this study aimed to evaluate possible alterations in the mtDNA copy number in SS. We have analyzed the amount of mtDNA in the peripheral blood of 74 SS patients and 61 healthy controls by qPCR. Then, since mitochondrial fusion and fission play a crucial role in maintaining the number of mitochondria, we investigated the expression variability of the genes most commonly involved in mitochondrial dynamics in a subgroup of SS patients and healthy controls. Interestingly, we observed a highly significant decrease in mtDNA copies in the SS patients compared to healthy controls (p = 1.44 × 10−12). Expression levels of mitochondrial fission factor (MFF), mitofusin-1 (MFN1), and mitochondrial transcription factor A (TFAM) genes were analyzed, showing a statistically significant increase in the expression of MFF (p = 0.003) and TFAM (p = 0.022) in the SS patients compared to healthy controls. These results give further insight into the possible involvement of mitochondrial dysfunctions in SS disease.

  • Relapses of idiopathic inflammatory myopathies after vaccination against COVID-19: a real-life multicenter Italian study
    Edoardo Conticini, Miriana d’Alessandro, Silvia Grazzini, Marco Fornaro, Daniele Sabella, Giuseppe Lopalco, Federico Giardina, Serena Colafrancesco, Chiara Rizzo, Giuliana Guggino,et al.
    Springer Science and Business Media LLC
    AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination plays a crucial role as pivotal strategy to curb the coronavirus disease-19 (COVID-19) pandemic. The present study described the clinical status of patients affected by idiopathic inflammatory myopathies (IIM) after COVID-19 vaccination to assess the number of relapses. We included all patients affected by IIM and followed by Myositis Clinic, Rheumatology and Respiratory Diseases Units, Siena University Hospital, Bari University Hospital, Policlinico Umberto I, Sapienza University, Rome, and Policlinico Paolo Giaccone, Palermo. They underwent a telephone survey. A total of 119 IIM patients (median, IQR 58 (47–66) years; 32males; 50 dermatomyositis, 39 polymyositis and 30 anti-synthetase syndrome) were consecutively enrolled. Except four patients who refused the vaccination, 94 (81.7%) received Comirnaty, 16 (13.9%) Spikevax, 5 (4.4%) Vaxzevria. Seven (6.1%) patients had flare after vaccination. One of them had life-threatening systemic involvement and died two months after second dose of COVID-19 vaccination. From logistic regression analysis, Chi2-log ratio = 0.045,the variable that most influences the development of flare was the number of organs involved (p = 0.047). Sixty-eight patients received the third dose of COVID-19 vaccination: 51(75%) Comirnaty and 17 (25%) Moderna. No patients had flares after third dose. Our study represents the largest cohort of IIM patients in which the incidence of recurrence after anti-SARS-CoV-2 vaccine was assessed. In line with real-life data from other diseases, we found a clinical non-statistically significant risk of relapse in our patients, which occurred seldom, usually mild and in patients with a more severe and aggressive course of disease.

  • Are interferon-gamma release assays reliable to detect tuberculosis infection in patients with rheumatoid arthritis treated with Janus kinase inhibitors?
    Rossana Scrivo, Emanuele Molteni, Chiara Castellani, Alessio Altobelli, Cristiano Alessandri, Fulvia Ceccarelli, Manuela Di Franco, Roberta Priori, Valeria Riccieri, Antonio Sili Scavalli,et al.
    Public Library of Science (PLoS)
    Background Screening for latent tuberculosis infection is recommended in patients with rheumatoid arthritis (RA) starting Janus kinase inhibitors (Jaki). Interferon (IFN)-gamma release assays (IGRAs) are increasingly used for this purpose. Jaki tend to decrease the levels of IFNs, questioning the reliability of IGRAs during treatment with these drugs. Objectives To compare the performance of QuantiFERON-TB Gold Plus (QFT-P) and QFT Gold In-tube (QFT-GIT) in RA patients treated with Jaki. Methods RA patients underwent QFT-P and QFT-GIT at baseline (T0), and after 3 (T3) and 12 months (T12) of treatment with Jaki. The agreement between the two tests was calculated. The agreement between IGRAs and tuberculin skin test (TST) or chest radiography at baseline was also determined. The variability of QTF-P results was longitudinally assessed. Results Twenty-nine RA patients (F/M 23/6; median age/IQR 63/15.5 years; median disease duration/IQR 174/216 months) were enrolled. A perfect agreement was found between QFT-P and QFT-GIT at all times (κ = 1). At T0, no agreement was recorded between IGRAs and TST (κ = -0.08) and between TST and chest radiography (κ = -0.07), a low agreement was found between QFT-P and chest radiography (κ = 0.17). A variation of 33.3% in the results of QFT-P was recorded at T3 vs T0, of 29.4% at T12 vs T0, and of 11.8% at T12 vs T3. The median levels of IFN-γ produced by lymphocytes in response to the mitogen of QFT-P decreased after 3 months followed by an increase after 12 months (not significant). No change in the median number of circulating lymphocytes was documented. Glucocorticoids intake was associated with a higher probability of negative or indeterminate IGRA results at T0 (p&lt;0.0001). Conclusion A response to IGRAs is detectable during treatment with Jaki. However, fluctuations in the results of IGRAs have been observed in the absence of correlation with clinical outcomes, thus challenging their interpretation.

  • Imaging Activated-T-Lymphocytes in the Salivary Glands of Patients with Sjögren’s Syndrome by <sup>99m</sup>Tc-Interleukin-2: Diagnostic and Therapeutic Implications
    G. Campagna, L. K. Anzola, M. Varani, C. Lauri, Guido Gentiloni Silveri, Lorenzo Chiurchioni, F. Spinelli, R. Priori, F. Conti and A. Signore

    Background: Sjögren’s syndrome (SS) is a progressive autoimmune disease characterized by local mononuclear cell infiltration of the salivary and lachrymal glands. Labial biopsy demonstrates local infiltration by Th1 cells that produce pro-inflammatory cytokines, such as interleukin-2 (IL2). The aim of this study was to assess the utility of 99mTc-labelled-IL2 (99mTc-IL2) in evaluating in vivo the extent and severity of lympho-mononuclear cell infiltration in the salivary glands of patients with SS. Methods: We investigated 48 patients with primary SS and 27 control subjects using 99mTc-IL2 scintigraphy. Furthermore, in a subgroup of 30 patients, we also performed 99mTc-pertechnetate scintigraphy (99mTcO4−) for evaluation of the salivary gland function. Results: 99mTc-IL2 uptake in the salivary glands of SS patients was higher than in the control subjects (1.30 ± 0.16 vs. 0.83 ± 0.08 for parotids and 1.36 ± 0.15 vs. 1.16 ± 0.07 for submandibular glands; p < 0.0001). The salivary gland uptake of 99mTc-IL2 in patients with a longer history of disease was lower compared with the recently diagnosed patients. A significant direct correlation was found between the uptake of 99mTc-IL2 and histology. Conclusions: 99mTc-IL2 scintigraphy showed that the degree of lymphocytic infiltration of major salivary glands is variable in patients with different disease durations. Patients with a high 99mTc-IL2 uptake could be efficiently treated with immuno-modulatory drugs and the efficacy of treatment could be followed-up by 99mTc-IL2 scintigraphy.

  • The role of musculoskeletal ultrasound in predicting the response to JAK inhibitors: results from a monocentric cohort
    Fulvia Ceccarelli, Francesca Romana Spinelli, Cristina Garufi, Silvia Mancuso, Cristiano Alessandri, Manuela Di Franco, Valeria Orefice, Viviana Antonella Pacucci, Carmelo Pirone, Roberta Priori,et al.
    Clinical and Experimental Rheumatology
    OBJECTIVES In this longitudinal study, we assessed the role of musculoskeletal ultrasound (US) in predicting the efficacy of JAK inhibitors (JAKi) in rheumatoid arthritis (RA) patients. METHODS We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by Disease Activity Score 28 (DAS28CRP); US examination in 22 joints (I-V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), scored through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I-V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score ranging from 0 to 22. RESULTS We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). At multivariate analysis, PD and tenosynovitis score significantly correlated with changes in DAS28CRP. CONCLUSIONS The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, we found that power Doppler and tenosynovitis scores could play a predictive role in response to treatment.

  • Hydroxychloroquine cardiotoxicity: a case-control study comparing patients with COVID-19 and patients with systemic lupus erythematosus
    Silvia Mancuso, Francesca Romana Spinelli, Luciano Agati, Maria Rosa Ciardi, Cristina Garufi, Francesco Natalucci, Emanuele Molteni, Simona Truglia, Valeria Riccieri, Roberta Priori,et al.
    Clinical and Experimental Rheumatology
    OBJECTIVES Antimalarials have been associated with QT prolongation in COVID-19 patients but are generally safe in systemic lupus erythematosus (SLE).We compared the prevalence of QTc prolongation between COVID-19 and SLE patients treated with hydroxychloroquine (HCQ). METHODS We included patients with SARS-CoV-2 infection confirmed by nasopharyngeal swab and patients taking HCQ for SLE. A prolonged QTc was defined as an increase in QTc intervals >60 ms (compared with baseline) or as a QTc of ≥500 ms. We performed the univariate and multivariate logistic regression to investigate the risk factors for QTc prolongation in COVID-19 patients. RESULTS We enrolled 58 COVID-19 patients (median age 70.5 years, IQR 25), grouped into group A (patients with HCQ) group B (patients with HCQ + azithromycin) and group C (not received either drug). Fifty (26%) COVID-19 patients presented a QTc prolongation (12 QTc≥500 ms, 3 patients ΔQTc>60 ms). We did not find any differences in QTc prolongation among the three treatment groups. Baseline QTc (OR 111.5) and D-dimer (OR 78.3) were independently associated to QTc prolongation. Compared to the 50 SLE patients (median age 38.5 years, IQR 22), chronically treated with HCQ, COVID-19 patients showed significantly longer QTc (p<0.001). CONCLUSIONS This is the first study demonstrating that, unlike COVID-19 patients, patients with SLE are not susceptible to HCQ-induced long QT syndrome and arrhythmia. The combined arrhythmogenic effect of SARS-CoV-2 infection and HCQ could account for the excess of QTc prolongation and fatal arrhythmias described in patients with COVID-19.

  • Maladaptive Autophagy in the Pathogenesis of Autoimmune Epithelitis in Sjögren's Syndrome
    Serena Colafrancesco, Cristiana Barbati, Roberta Priori, Erisa Putro, Federico Giardina, Angelica Gattamelata, Benedetta Monosi, Tania Colasanti, Alessandra Ida Celia, Bruna Cerbelli,et al.
    Wiley
    OBJECTIVE Salivary gland epithelial cells (SGECs) are key cellular drivers in the pathogenesis of primary Sjӧgren's Syndrome (pSS); however, the mechanisms sustaining SGECs activation in pSS remain undetermined. The aim of this study is to determine the role of autophagy in the survival and activation of SGECs in pSS. METHODS Primary SGECs isolated from minor salivary glands (SG) of patients with pSS or sicca syndrome were evaluated by flow-cytometry, immunoblotting, and immunofluorescence to assess autophagy (autophagic-flux, LC3IIB, p62, LC3B+/LAMP1+ staining), apoptosis (annexin V/PI, Caspase-3) and activation (ICAM, VCAM). Focus score and germinal centers presence was assessed in SG from the same patients to correlate with histological severity. Human salivary gland (HSG) cells were stimulated in vitro with PBMCs and serum from pSS patients in the presence or absence of autophagy inhibitors to determine changes in autophagy and epithelial cell activation. RESULTS SGECs from pSS patients (n=24) exhibited increased autophagy (autophagic-flux p=0.001; LC3IIB p=0.02; p62 p=0.064; LC3IIB/LAMP1+ staining), increased expression of anti-apoptotic molecules (Bcl2 p=0.006), and reduced apoptosis (Annexin-V/PI p=0.002, Caspase-3 p=0.057) compared to sicca (n=16). Autophagy correlated with histologic disease severity. In vitro experiments on HSG cells stimulated with serum and PBMCs from pSS patients confirmed activation of autophagy and expression of adhesion molecules, which was reverted upon pharmacologic inhibition of autophagy. CONCLUSIONS In pSS SGECs, inflammation induces autophagy and pro-survival mechanisms, which promote SGEC activation and mirror histological severity. These findings indicate that autophagy is a central contributor to the pathogenesis of pSS and a new therapeutic target.

  • Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts
    Vasileios C. Pezoulas, Andreas Goules, Fanis Kalatzis, Luke Chatzis, Konstantina D. Kourou, Aliki Venetsanopoulou, Themis P. Exarchos, Saviana Gandolfo, Konstantinos Votis, Evi Zampeli,et al.
    Elsevier BV

  • Cutaneous vasculitis following COVID-19 vaccination
    Giulio Cavalli, Serena Colafrancesco, Giacomo De Luca, Nathalie Rizzo, Roberta Priori, Fabrizio Conti, and Lorenzo Dagna
    Elsevier BV

  • Resilience in women with primary Sjögren’s syndrome
    Roberta Priori, Federico Giardina, Raffaella Izzo, Angelica Gattamelata, Massimo Fusconi, Serena Colafrancesco, and Giuseppe Curcio
    Springer Science and Business Media LLC
    To assess the relationship between resilience and several diseases and individual features in primary Sjӧgren's Syndrome (SS) patients. Resilience was assessed using the Resilience Scale (RS-14). Disease activity, damage, and reported symptoms were assessed by means of ESSDAI (EULAR Sjögren's syndrome disease activity index), SSDDI (Sjӧgren's Syndrome Disease Damage Index) and ESSPRI (EULAR Sjӧgren's Syndrome Patient Reported Index). EuroQol, HADS (Hospital Anxiety and Depression Scale), SF-12 (Short-form 12 health survey), FAS (Fatigue Assessment Scale), FACIT-F (Functional Assessment of Chronic Illness Therapy – Fatigue), and IPAQ (International Physical Activity Questionnaire) questionnaires were submitted to evaluate physical and mental well-being of the recruited patients. Data about the autoimmune profile, systemic manifestations, and current therapy were collected. Educational qualifications and work activities were also considered. Descriptive, correlational, and linear regression analysis were performed. 74 consecutive women with primary SS and 74 sex and age-matched healthy subjects as a control group were recruited. SS patients displayed a moderate value of resilience (median 78.5) with no significant difference compared to controls (p = 0.38). An inverse relationship was found between resilience and mood disorders such as anxiety (p = 0.038) and depression (p < 0.001). Greater resilience was associated with a better perception of the quality of life (p = 0.02) and general health (p < 0.001), as well as with less fatigue (p = 0.008) and a more physically active lifestyle (p = 0.001). No significant relationship was found neither between resilience and age, socio-demographic and disease characteristics, nor with ESSDAI (p = 0.26), ESSPRI (p = 0.83) and SSDDI (p = 0.67). This is the first study assessing resilience in a large group of unselected primary SS patients. Most resilient primary SS patients are less depressed and show a better perception of their health. Greater resilience tends to correlate with less anxiety, physical and mental fatigue, and a more active lifestyle, while no association with disease activity and duration, damage, and socio-demographic features was detected. Considering the well-known role of resilience in helping to better cope with chronic illnesses, its assessment in SS patients should not be overlooked and the possible strategies for its improvement should be better explored and further implemented.