Publications by authors named "Ourania D Argyropoulou"

15 Publications

  • Page 1 of 1

Occurrence and Antigenic Specificity of Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) in Systemic Autoimmune Diseases.

Cells 2021 Aug 19;10(8). Epub 2021 Aug 19.

Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) recognize heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. Although P-ANCA have diagnostic utility in vasculitides, they may also be found in patients with various other systemic autoimmune rheumatic diseases (SARDs). Nevertheless, the clinical significance and the targets recognized by P-ANCA in such patients remain unclear. For this purpose, herein we investigated the occurrence of ANCA-related antigenic specificities in 82 P-ANCA-positive sera by multiplex ELISA, as well as their association with other autoantibodies. The P-ANCA-positive sera corresponded to patients with vasculitides ( = 24), systemic lupus erythematosus ( = 28), antiphospholipid syndrome ( = 5), Sjögren's syndrome ( = 7), rheumatoid arthritis ( = 3), systemic scleroderma ( = 1), sarcoidosis ( = 1) and Hashimoto's thyroiditis ( = 13). In most P-ANCA-positive patients studied (51/82, 62.3%), these autoantibodies occurred in high titers (>1:160). The analysis of P-ANCA-positive sera revealed reactivity to MPO in only 50% of patients with vasculitides, whereas it was infrequent in the other disease groups studied. Reactivity to other P-ANCA-related autoantigens was also rarely detected. Our findings support that high P-ANCA titers occur in SARD. The P-ANCA-positive staining pattern is associated with MPO specificity in vasculitides, while in other autoimmune diseases, it mostly involves unknown autoantigens.
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http://dx.doi.org/10.3390/cells10082128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393570PMC
August 2021

Neutrophil extracellular traps in giant cell arteritis biopsies: presentation, localization and co-expression with inflammatory cytokines.

Rheumatology (Oxford) 2021 Jul 14. Epub 2021 Jul 14.

Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Objectives: To explore the presence of neutrophil extracellular traps (NETs) in inflamed temporal artery biopsies (TABs) of patients with giant cell arteritis (GCA).

Methods: Ten patients with GCA [5 with limited and 5 with associated generalized vascular involvement, as defined by 18F-fluorodeoxyglucose (FDG) positron-emission tomography with computed tomography (PET/CT)] and 8 with polymyalgia rheumatica (PMR) were studied. The presence, location, quantitation, and decoration of NETs with IL-6, IL-1β, and IL-17A were assessed in TABs at the time of disease diagnosis by tissue immunofluorescence and confocal microscopy. Paired serum levels of IL-6 and IL-17A were also evaluated in all patients.

Results: All temporal artery biopsies from GCA, but not PMR patients, had NETs located mainly in the adventitia, adjacent to the vasa vasorum. NETs decorated with IL-6 were present in 8/10 TABs of GCA patients, of whom 5 were -PET/CT(+) and 3 PET/CT(-) patients. IL-17A(+) NETs were observed in all GCA patients. IL-1β(+)NETs were not detected in any GCA patient. No relation was found between serum IL-6 and IL-17A levels and NETs containing IL-6 and/or IL-17A.

Conclusions: NETs bearing pro-inflammatory cytokines are present in inflamed GCA-TABs. Future studies with a larger number of patients from different centers will show whether the findings regarding neutrophils/NETs in the TAB are consistent and disclose their clinical impact.
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http://dx.doi.org/10.1093/rheumatology/keab505DOI Listing
July 2021

Primary Sjögren's Syndrome of Early and Late Onset: Distinct Clinical Phenotypes and Lymphoma Development.

Front Immunol 2020 19;11:594096. Epub 2020 Oct 19.

Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Objectives: To study the clinical, serological and histologic features of primary Sjögren's syndrome (pSS) patients with early (young ≤35 years) or late (old ≥65 years) onset and to explore the differential effect on lymphoma development.

Methods: From a multicentre study population of 1997 consecutive pSS patients, those with early or late disease onset, were matched and compared with pSS control patients of middle age onset. Data driven analysis was applied to identify the independent variables associated with lymphoma in both age groups.

Results: Young pSS patients (19%, n = 379) had higher frequency of salivary gland enlargement (SGE, lymphadenopathy, Raynaud's phenomenon, autoantibodies, C4 hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3% vs. 5.7%, p = 0.030, OR = 1.91, 95% CI: 1.11-3.27), while old pSS patients (15%, n = 293) had more frequently dry mouth, interstitial lung disease, and lymphoma (6.8% vs. 2.1%, p = 0.011, OR = 3.40, 95% CI: 1.34-8.17) compared to their middle-aged pSS controls, respectively. In young pSS patients, cryoglobulinemia, C4 hypocomplementemia, lymphadenopathy, and SGE were identified as independent lymphoma associated factors, as opposed to old pSS patients in whom SGE, C4 hypocomplementemia and male gender were the independent lymphoma associated factors. Early onset pSS patients displayed two incidence peaks of lymphoma within 3 years of onset and after 10 years, while in late onset pSS patients, lymphoma occurred within the first 6 years.

Conclusion: Patients with early and late disease onset constitute a significant proportion of pSS population with distinct clinical phenotypes. They possess a higher prevalence of lymphoma, with different predisposing factors and lymphoma distribution across time.
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http://dx.doi.org/10.3389/fimmu.2020.594096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604905PMC
June 2021

One year in review 2020: pathogenesis of primary Sjögren's syndrome.

Clin Exp Rheumatol 2020 Jul-Aug;38 Suppl 126(4):3-9. Epub 2020 Sep 29.

Rheumatology Unit, Department of Clinical and Experimental Rheumatology, University of Pisa, Italy.

The pathogenesis of primary Sjögren's syndrome (pSS) remains poorly understood. However, important efforts have been made during the last few months. In this review, following the others of this series we will summarise the most recent literature on pSS pathogenesis focusing in particular on new insights into pSS animal models, genetics and epigenetics, innate and adaptive immune system abnormalities and tertiary lymphoid structures. Hopefully, novel insights into pSS pathogenesis will pave the way to new therapeutic approaches to the disease improving patients' management and prognosis.
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October 2020

Sjögren's Syndrome: The Clinical Spectrum of Male Patients.

J Clin Med 2020 Aug 12;9(8). Epub 2020 Aug 12.

Pathophysiology Department, Athens School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Background: To compare the clinical, serological and histologic features between male and female patients with Sjögren's syndrome (SS) and explore the potential effect of gender on lymphoma development.

Methods: From a multicenter population (Universities of Udine, Pisa and Athens, Harokopion and Ioannina (UPAHI)) consisting of consecutive SS patients fulfilling the 2016 ACR/EULAR criteria, male patients were identified, matched and compared with female controls. Data-driven multivariable logistic regression analysis was applied to identify independent lymphoma-associated factors.

Results: From 1987 consecutive SS patients, 96 males and 192 matched female controls were identified and compared. Males had a higher frequency of lymphoma compared to females (18% vs. 5.2%, OR = 3.89, 95% CI: 1.66 to 8.67; = 0.0014) and an increased prevalence of serum anti-La/SSB antibodies (50% vs. 34%, OR = 1.953, 95% CI: 1.19 to 3.25; = 0.0128). No differences were observed in the frequencies of lymphoma predictors between the two genders. Data-driven multivariable logistic regression analysis revealed negative association of the female gender with lymphoma and positive association with lymphadenopathy.

Conclusion: Male SS patients carry an increased risk of lymphoma development. Although statistics showed no difference in classical lymphoma predictors compared to females, data-driven analysis revealed gender and lymphadenopathy as independent lymphoma-associated features.
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http://dx.doi.org/10.3390/jcm9082620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463756PMC
August 2020

Common and rare forms of vasculitis associated with Sjögren's syndrome.

Curr Opin Rheumatol 2020 01;32(1):21-28

Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Purpose Of Review: Although uncommon, systemic vasculitis is one of the most severe extraglandular manifestations of primary Sjögren's syndrome (pSS) accounting for the increased morbidity and mortality of the disease. This review aims to describe major previous and recent reports regarding the clinical presentation, prognosis and treatment of systemic vasculitis associated with pSS.

Recent Findings: Both older and recent pSS cohort studies performed over the past several and recent years, have clearly shown that cryoglobulinaemic vasculitis is the most frequent type of systemic vasculitis accompanying pSS. Antineutrophil cytoplasmic antibody-associated, large and medium vessel vasculitis are described only in sporadic cases. In addition to the overt clinical manifestations of cryoglobulinaemic vasculitis, type II cryoglobulinaemia, glomerulonephritis and purpura have been correlated with increased risk for B-cell non-Hodgkin lymphoma (NHL) in pSS.

Summary: pSS is characterized by autoreactive B and T-cell infiltrates around the epithelial structures of the affected organs, as well as, B-cell hyperreactivity. The latter, is attested by the increased production of autoantibodies, directed against many different organ and nonorgan self-antigens. Vasculitis is a significant and potentially life-threatening complication of the disease depending on the size, localization, histologic type and the pathogenetic mechanisms of the inflammatory process. The potentially irreversible tissue damage, as well as the increased risk for NHL development, prompts the need for early diagnosis and treatment of cryoglobulinaemic vasculitis in pSS.
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http://dx.doi.org/10.1097/BOR.0000000000000668DOI Listing
January 2020

Molecular and clinical spectrum of four pedigrees of TRAPS in Greece: results from a national referral center.

Rheumatology (Oxford) 2020 06;59(6):1241-1246

Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Objective: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominantly inherited autoinflammatory disease caused by mutations of the TNFRSF1A gene. To address the association between TNFRSF1A mutations and clinical phenotype, we analyzed four pedigrees of TRAPS patients.

Methods: Four Greek patients with TRAPS-like clinical features were screened for TNFRSF1A mutations by sequencing exons 2, 3 and 4. Following positive testing, twenty-two members of their families were also genetically and clinically screened.

Results: Twenty-six members of four unrelated Greek families were investigated. The C73Y (c.305G>A) mutation of the TNFRSF1A gene was identified in five patients, with two of the five carrying a concomitant R92Q variation. We also identified seven C73W (c.306C>G), two T50M (c.236C>T) and seven R92Q (c.362G>A) carriers. Symptoms varied and the C73Y, C73W and T50M mutations were associated with the most severe clinical manifestations. The R92Q phenotype ranged from asymptomatic to mild disease. Molecular modelling linked pathogenicity with aberrant TNFRSF1A disulphide bond formation.

Conclusion: In this first pedigree analysis of TRAPS in Greece, we identified the rare C73Y TNFRSF1A mutation. A wide clinical spectrum was observed with the C73Y, C73W and T50M mutations that affect TNFRSF1A disulphide bonds and are associated with worse symptoms.
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http://dx.doi.org/10.1093/rheumatology/kez424DOI Listing
June 2020

One year in review 2019: Sjögren's syndrome.

Clin Exp Rheumatol 2019 May-Jun;37 Suppl 118(3):3-15. Epub 2019 Jul 16.

Rheumatology Unit, Department of Medicine, University of Perugia, Italy.

Primary Sjögren's syndrome (pSS) is a complex and heterogeneous disorder characterised by a wide spectrum of glandular and extra-glandular features. Novel insights into disease pathogenesis and the discovery of novel biomarkers are allowing us to characterise the disease not only phenotypically on the basis of clinical presentation, but also on the basis of the endotype. Ultimately, a better stratification of patients may pave new avenues for novel targeted therapies, opening new possibilities for the application of personalised medicine in pSS.
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October 2019

Autoimmune epithelitis beyond the exocrine glands: an unusual case of anti-Ro/La and Scl-70 lymphocytic interstitial pneumonia.

Clin Exp Rheumatol 2019 May-Jun;37 Suppl 118(3):249-251. Epub 2019 Jul 19.

Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece.

Objectives: Interstitial lung disease is a life-threatening complication of many systemic autoimmune diseases with diverse clinical and histopathological features. Among them, lymphocytic interstitial pneumonia (LIP) is mainly associated with primary Sjögren's syndrome (pSS). A case of a middle-aged man with LIP, anti-Ro/La, anti-Scl70 autoantibodies and overlapping histopathological features of pSS and systemic sclerosis (SSc) is presented and discussed.

Methods: A 65-year-old man complaining for easy fatigue and dry cough was evaluated. Physical examination revealed bibasilar crackles on auscultation. Imaging tests showed areas of centrilobular nodules with tree-in-bud sign on the medial lobe of the right lung. Pulmonary function tests demonstrated small airways disease. Laboratory evaluation revealed elevated ESR and CRP, ANA titre >1/320, positive Ro52, Ro60 and La autoantibodies but also, weakly positive anti Scl70 autoantibody.

Results: Right lobe lung biopsy showed diffuse fibrosis with altered alveolar architecture and diffuse infiltration of alveolar septa by lymphocytes and mast cells. Ectopic germinal centres were disclosed, adjacent to the small bronchi causing lumen obstruction and validated after the demonstration of CD23 expression, specific for follicular dendritic cells. Biopsy of minor salivary glands revealed intense periductal fibrosis with limited round cell infiltrates, not fulfilling the histopathological criteria for pSS. The diagnosis of LIP was established and the patient received corticosteroids with poor response. Subsequently he was treated with rituximab with satisfactory results.

Conclusions: This case with LIP and disease-specific autoantibodies for pSS and SSc teaches the complexity and overlapping nature of both diseases, extending from autoimmune epithelitis with ectopic germinal centres to fibrosis-related SSc. It points out the significance of the affected tissue biopsy, which may uncover the different disease phenotypes. To this end, treatment with anti-CD20, acting at the crossroads of the pathogenetic mechanisms of both diseases may serve as a first choice therapy.
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October 2019

Update on Sjögren's Syndrome 2018.

Mediterr J Rheumatol 2018 Dec 18;29(4):193-198. Epub 2018 Dec 18.

Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease with a diverse clinical picture, extending from exocrine involvement to extraglandular manifestations. Although pSS remains a disease of unknown etiology, an interaction between genetic susceptibility and environmental triggers is thought to play a key role in disease initiation and progress. Despite the extensive research during the past years, the pathogenetic mechanisms are still elusive and effective therapeutic intervention is still missing. This review aims to provide an overview of the recent literature on the pathogenesis, clinical features and new therapeutic aspects of pSS.
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http://dx.doi.org/10.31138/mjr.29.4.193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045943PMC
December 2018

Decrease in the ratio of polyreactive IgG titers with IgG concentration is associated with long-term complications of primary Sjögren's syndrome.

Clin Exp Rheumatol 2018 May-Jun;36 Suppl 112(3):239-240. Epub 2018 Aug 14.

Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece.

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November 2018

One year in review 2018: Sjögren's syndrome.

Clin Exp Rheumatol 2018 May-Jun;36 Suppl 112(3):14-26. Epub 2018 Jul 18.

Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.

Sjögren's syndrome is a complex and potentially disabling slow progressive, systemic disorder. During the last twelve months several original and important contributions have been published on the pathogenesis, diagnosis and therapy of the disease. This review, following the others of this series is aimed at summarising some of the most significant studies that have been recently published. Regarding the pathogenesis, we will specifically focus on novel insights on miRNA, gut microbiota, adaptive and innate autoimmunity and animal models. Concerning novelties in pSS diagnosis, we will focus on salivary gland ultrasonography and histology. Finally, we will conclude with an update of the clinical manifestations of the disease and with an overview of the future therapies.
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November 2018

Severe cutaneous hand infection: Mycobacterium marinum in an immunosuppressed patient.

Clin Exp Rheumatol 2018 Nov-Dec;36(6):1117. Epub 2018 Jul 19.

Department of Pathophysiology, School of Medicine, National & Kapodistrian University of Athens; Institute for Autoimmune Systemic and Neurological Diseases, Athens; and Academy of Athens, Greece.

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March 2019

Myositis autoantibody profiles and their clinical associations in Greek patients with inflammatory myopathies.

Clin Rheumatol 2019 Jan 25;38(1):125-132. Epub 2018 Aug 25.

Institute for Systemic Autoimmune and Neurological Diseases, Athens, Greece.

Myositis-specific (MSAs) or-associated autoantibodies (MAAs) have been linked to particular clinical phenotypes of idiopathic inflammatory myopathies (IIM) and appear to aid diagnosis. The objective of this study was to analyze the prevalence of MSAs and MAAs and their possible clinical associations in Greek IIM patients. This study comprised 95 IIM patients classified based on the 2017 EULAR/ACR classification criteria. All patients had MSAs and MAAs measured in their sera by line immunoblot assay. Dermatomyositis was the most prevalent IIM clinical subtype. MSAs were found in 44% of the patients, whereas MAAs in 23%. The most frequently detected MSA was anti-Jo-1 (22%), while the most frequently detected MAA was anti-Ro-52 (30%). The distributions of MSAs/MAAs did not differ between the five IIM subgroups, except for anti-Mi-2 which was only detected in dermatomyositis patients. Patients with at least one MSA and/or MAA positivity showed more frequently IIM characteristic skin rashes, while those presenting solely MAA positivity had more often puffy hands and Raynaud's phenomenon. Anti-Jo1-positive patients presented more frequently lung disease, while anti-Ro52 positivity related to mechanic's hands. Anti-Ro-52 and anti-Jo-1 strongly associated with one another. Prevalence of IIM subtypes and of MSAs/MAAs in our patients is in line with published reports in populations of similar geographic distribution. While MSA and/or MAA positivity did associate with particular clinical manifestations, it did not predict in our cohort specific IIM subgroup as defined by the latest EULAR/ACR classification criteria. Future studies are warranted to conclusively decide if these autoantibodies, measured with a standardized method, should or not be incorporated in every day clinical practice to aid IIM diagnosis.
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http://dx.doi.org/10.1007/s10067-018-4267-zDOI Listing
January 2019

Accelerated atheromatosis and arteriosclerosis in primary systemic vasculitides: current evidence and future perspectives.

Curr Opin Rheumatol 2018 Jan;30(1):36-43

1st Department of Propaedeutic Internal Medicine, Medical School, Laikon Hospital, National and Kapodistrian University of Athens, Greece.

Purpose Of Review: Primary systemic vasculitides (PSV) encompass a subset of autoimmune diseases, characterized by inflammation of blood vessels. Atheromatosis and arteriosclerosis may be accelerated in several PSV and account for the increased rate of cardiovascular morbidity that some exhibit. We aimed to summarize recent studies reporting on the acceleration of atheromatosis and/or arteriosclerosis in each type of PSV, using state-of-the-art noninvasive vascular biomarkers with clinical value as end points.

Recent Findings: Limited number of PSV patients and methodology limitations reduce the value of many published studies. Accelerated atheromatosis, as measured by the use of carotid ultrasonagraphy (plaques and intimal-medial thickening) and increased arterial stiffening, as measured by the use of applanation tonometry (carotid to femoral pulse wave velocity), are currenly well established in Takayasu arteritis, Kawasaki disease and Behcet's disease. The association of atheromatosis and arteriosclerosis with polyarteritis nodosa and small vessel vasculitides remains less established and studied, so far.

Summary: Accelerated atheromatosis and arteriosclerosis or arteriosclerosis are established in some PSV. The potential clinical value of easy-to-measure and clinically useful noninvasive vascular biomarkes prompts the need for large prospective cohorts in order to provide useful future guidance regarding the prognosis and treatment of PSV patients.
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http://dx.doi.org/10.1097/BOR.0000000000000453DOI Listing
January 2018
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