Clio Mavragani

National and Kapodistrian University of Athens | uoa · Department of Physiology

Introduction: Myopathies are heterogeneous neuromuscular diseases of genetic and/or inflammatory etiology that affect both cardiac and skeletal muscle. We investigated the prevalence of cardiac inflammation in patients with myopathies, cardiovascular symptoms, and normal echocardiography using cardiovascular magnetic resonance (CMR). Methods: We...

Objectives To investigate the expression of type I interferon (IFN-I) and neutrophil transcripts in kidney tissue from patients with distinct classes of lupus nephritis and their association with clinical and histopathological features. Patients and Methods Quantitation of IFN-I and defensin-α3 transcripts was performed in kidney biopsies from 24...

Systemic sclerosis (SSc) has been classically linked to interstitial lung disease (ILD) development, often in association with specific SSc autoantibodies. In the present report, we aimed to estimate the prevalence of SSc autoantibodies in 60 seropositive RA and 41 primary SS patients complicated or not by ILD. SSc autoantibodies were determined in...

Type I interferons (IFNs) are major mediators of innate immunity, with well-known antiviral, antiproliferative, and immunomodulatory properties. A growing body of evidence suggests the involvement of type I IFNs in the pathogenesis of central nervous system (CNS) manifestations in the setting of chronic autoimmune and autoinflammatory disorders, wh...

Objectives To investigate the expression of type I IFN (IFN-I) and neutrophil transcripts in kidney tissue from patients with different classes of LN and their association with distinct clinical and histopathological features. Methods Quantitation of IFN-I, defensin-α3 and formyl peptide receptor-like 1 (FPRL-1) transcripts was performed in kidney...

Background/Objective Older age and male sex have been consistently found to be associated with dismal outcomes among COVID-19 infected patients. In contrast, premenopausal females present the lowest mortality among adults infected by SARS-CoV-2. The goal of the present study was to investigate whether peripheral blood type I interferon (IFN) signat...

Objective: While multiple sclerosis (MS) is considered the cornerstone of autoimmune demyelinating CNS disorders, systemic autoimmune diseases (SADs) are important MS mimickers. We sought to explore whether distinct clinical, laboratory, and imaging characteristics along with quantitation of peripheral blood type I interferon (IFN) activity could a...

Objectives: Rheumatoid Arthritis (RA) and primary Sjögren's Syndrome (SS) carry increased atherosclerotic risk, while B cell activating factor holds a vital role in disease pathogenesis and atherosclerosis. We aimed to compare subclinical atherosclerosis profiles between the two clinical entities and define whether BAFF genetic variants alter athe...

We aimed to explore whether the rs2073618 variant (G1181C) of the osteoprotegerin (OPG) gene and the methylenetetrahydrofolate reductase (MTHFR) rs1801131 (A1298AC) and rs1801133 (C677T) gene polymorphisms contribute to rheumatoid arthritis (RA) susceptibility and RA related subclinical atherosclerosis. Overall 283 RA patients and 595 healthy contr...

Clinical data on vaccinated patients with coronavirus disease (COVID-19) who have systemic autoimmune and autoinflammatory rheumatic diseases (SAARD) are limited. The observational study aimed to report the clinical features and outcomes of COVID-19 among cases with SAARD that were unvaccinated or were 2- and 3-dose vaccinated against SARS-CoV-2 an...

Objectives Sicca complaints are a frequent reason for rheumatologic consultation. Testing for specific antibodies against Ro/SSA and La/SSB antigens and minor salivary gland (MSG) biopsy are among the main tools implemented in the diagnostic work-up. Anticentromere antibodies and sicca manifestations are frequently detected in Sjögren's syndrome (S...

Vitamin D is an agent involved in bone and mineral homeostasis. It has been recognized as a potent immunomodulator. It has immune-enhancing properties, and it induces immune tolerance. Vitamin D deficiency has been shown to be related to the development of autoimmune disorders. Vitamin D deficiency has been observed in patients with rheumatoid arth...

Since its discovery, vitamin D was shown to have both immunostimulatory and immunomodulatory effects on the immune system. A growing body of evidence so far linked vitamin D deficiency with the development and severity of several systemic and organ specific autoimmune/inflammatory diseases, such as systemic lupus erythematosus, rheumatoid arthritis...

Background/Purpose Primary Sjögren’s Syndrome (SS) is characterized by B lymphocyte hyperactivity with B cell activating factor (BAFF) acting as an important regulator. Single Nucleotide Polymorphisms (SNPs) of the BAFF gene have been implicated in the pathogenesis of several autoimmune diseases characterized by heightened fatigue levels, including...

Increased expression of interferon (IFN)-stimulated genes (ISGs) in peripheral blood, has been previously reported in viral infections, as well as in autoimmune disorders, in association with reduced leukocyte and platelet counts. Though cytopenias are common in patients with COVID-19 disease and predict severe outcomes, the underlying mechanisms h...

Primary Sjögren’s syndrome (SS) is a chronic systemic autoimmune disorder affecting primarily perimenopausal women [...]

Sjogren’s syndrome (SS) is a systemic autoimmune rheumatic disease primarily affecting lachrymal and salivary glands, leading to dry eyes and dry mouth, respectively. Virtually any organ/system can be affected and respiratory involvement is quite common among SS patients. It is heterogeneous and primarily manifests as airway and interstitial lung d...

A notable feature of immune checkpoint inhibitor (ICI) therapy in oncology patients is its association with increased frequency of immune related adverse reactions, directly associated with their unique mechanism of action. These adverse events are of great interest to rheumatologists, as not only do they commonly require immunosuppressive therapeu...

With the increasing number of indications for checkpoint inhibitor therapy in cancer patients, rheumatology specialists are often involved in the diagnosis and management of immune-related adverse events (irAEs). The most common rheumatic irAEs are arthritis, sicca syndrome, polymyalgia rheumatica, and myositis. Eosinophilic fasciitis, an already r...

Exertional chest pain/dyspnea or chest pain at rest are the main symptoms of coronary artery disease (CAD), which are traditionally attributed to insufficiency of the epicardial coronary arteries. However, 2/3 of women and 1/3 of men with angina and 10% of patients with acute myocardial infarction have no evidence of epicardial coronary artery sten...

Objective: To explore whether the osteoprotegerin (OPG) rs2073618 gene variant and the methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133 polymorphisms contribute to rheumatoid arthritis (RA) susceptibility and RA related subclinical atherosclerosis. Methods: 283 RA patients and 595 healthy controls (HC) were genotyped for OPG and...

Objective Adenosine deaminase acting on RNA-1 (ADAR1) enzyme is a type I interferon (IFN)-stimulated gene (ISG) catalyzing the deamination of adenosine-to-inosine, a process called A-to-I RNA editing. A-to-I RNA editing takes place mainly in Alu elements comprising a primate-specific level of post-transcriptional gene regulation. Whether RNA editin...

Objective We investigated whether interferon (IFN) induced genes could serve as biomarkers for the detection of lymphoma development among patients with Sjögren's syndrome (SS). Methods Total RNA was extracted from 98 labial minor salivary glands (LMSG) biopsies of SS patients [61 not complicated by lymphoma (SS-nL) and 37 complicated by Non-Hodgk...

Background: Alterations of the insulin-like growth factor (IGF) pathway along with genetic variations of the IGF1 receptor (IGF1R) gene have been linked to the development of systemic autoimmunity, possibly through apoptosis induction. This study aims to investigate whether genetic variations of the IGF1R contribute to Sjögren's syndrome (SS) path...

The impact of COVID-19 infection in patients with autoimmune/auto-inflammatory rheumatic diseases (AARD) under immunomodulatory treatment has been a focus of interest during the SARS-CoV-2 pandemic. In this observational study, demographic data, disease related features and comorbidities, COVID-19 manifestations and outcome, as well as antibody res...

Rheumatoid Arthritis (RA) is a common chronic inflammatory disorder affecting 0,5-1% of the population, characterised by intense cellular activation and inflammation in the affected joints ultimately leading to bone and cartilage destruction. Cardiovascular disease is the leading cause of death among patients suffering from RA, with chronic inflamm...

Introduction Accumulating data highlights that dysregulation of type I interferon (IFN) pathways plays a central role in the pathogenesis of several systemic and organ specific autoimmune diseases. Advances in understanding the role of type I IFNs in these disorders can lead to targeted drug development as well as establishing potential disease bio...

Background Primary Sjögren Syndrome (SS) is a slowly progressive systemic autoimmune disease complicated by lymphoma, with mucosa associated lymphoid tissue (MALT) type being the most common lymphoma form. Several predictors related to pSS associated lymphomas have been described, but there are no studies focusing on specific risk factors for the M...

Background Sjögren’s Syndrome (SS) is a chronic systemic autoimmune disease of unknown etiology, carrying the highest lymphoma risk among autoimmune diseases, with significant impact on mortality and morbidity of patients. Objectives To describe: i) the clinical phenotype of SS, ii) the histologic type, stage, treatment options regarding lymphomas...

Background Primary Systemic Vasculitides (PSV) constitute a heterogeneous group of rare and potentially life-threatening autoimmune diseases, characterized by a varying degree of inflammatory response, leading to local or generalized vascular disease. Vessel involvement accounts for the micro- and macrovascular complications of the disease, along w...

Whether and how an acute immune challenge may affect DNA Damage Response (DDR) is unknown. By studying vaccinations against Influenza and SARS-CoV-2 (mRNA-based) we found acute increases of type-I interferon-inducible gene expression, oxidative stress and DNA damage accumulation in blood mononuclear cells of 9 healthy controls, coupled with effecti...

Background B-cell non-Hodgkin’s lymphoma (B-NHL) is one of the major complications of primary Sjögren’s syndrome (SS). Chronic inflammation and macrophages in SS minor salivary glands have been previously suggested as significant predictors for lymphoma development among SS patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2)—a product mainl...

The aim of this study is to explore the role of labial minor salivary gland (LMSG) focus score (FS) in stratifying Sjögren's Syndrome (SS) patients, lymphoma development prediction and to facilitate early lymphoma diagnosis. Ιn an integrated cohort of 1997 patients, 618 patients with FS ≥ 1 and at least one-year elapsing time interval from SS diagn...

Sjögren’s syndrome (SS) is a chronic systemic autoimmune disease that affects predominately salivary and lacrimal glands. SS can occur alone or in combination with another autoimmune disease like systemic lupus erythematosus (SLE). Here we report that TLR7 signaling drives the development of SS since TLR8-deficient (TLR8ko) mice that develop lupus...

Sjogren’s syndrome (SS) is a frequent entity with a broad symptomatology spectrum, mainly affecting the salivary and lachrymal glands. The disease also affects the musculoskeletal system targeting bones, specific joints, muscles, and the peripheral nerve system. Disease related clinical manifestations canhave an accumulative impact, as the syndrome...

Non-sustained ventricular tachycardia (NSVT) is a potentially lethal arrhythmia that is most commonly attributed to coronary artery disease. We hypothesised that among patients with NSVT and preserved ejection fraction, cardiovascular magnetic resonance (CMR) would identify a different proportion of ischaemic/non-ischaemic arrhythmogenic substrates...

Background: Primary Sjogren's syndrome (SS) is an autoimmune disease with a strong predilection for lymphoma development, with earlier disease onset being postulated as an independent risk factor for this complication. Variations of the Leukocyte immunoglobulin-like receptor A3(LILRA3) gene have been previously shown to increase susceptibility for...

Autoinflammatory diseases have been considered for decades as syndromes of unknown etiology and their treatment was limited to traditional anti-inflammatory agents. Over the last years, our better understanding in disease pathogenesis has allowed the expansion of our therapeutic armamentarium towards autoinflammatory disorders with the implementati...

Raynaud’s phenomenon (RP) is a condition characterised by distinct colour changes of the digits upon exposure to sympathomimetic conditions, such as cold temperature. It can be either primary or secondary, depending on whether it presents alone or as part of an underlying disorder. One of the most common causes of secondary RP are systemic autoimmu...

Objective To explore whether APOBEC family members are involved in the response to inappropriate expression of L1 retroelements in primary Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE), as well as in SS related lymphomagenesis. Methods Minor salivary glands (MSG) and kidney biopsy (KB) specimens were obtained from 41 SS patients (...

Objective : To assess the efficacy and safety of the IL-1b inhibitor canakinumab in all adults with refractory Still's disease identified from the National Organization For Medicines for off-label drug use. Methods : In a retrospective longitudinal multicenter cohort of 50 patients (median age 39 years) with active Still's disease despite treatmen...

Increased endogenous DNA damage and type I interferon pathway activation have been implicated in systemic sclerosis (SSc) pathogenesis. Because experimental evidence suggests an interplay between DNA damage response/repair (DDR/R) and immune response, we hypothesized that deregulated DDR/R is associated with a type I interferon signature and/or fib...

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 dise...

Objective: A link between bone metabolism and cardiovascular (CV) disease has been suggested mainly in the general population. In the current study we explored whether altered bone metabolism influence CV risk in patients with SLE. Methods: In 138 consecutive patients with SLE, atherosclerosis was assessed by the presence of plaque and/or arteri...

Background Anti-TNF agents have revolutionized the treatment of chronic inflammatory disorders. Nevertheless, several adverse reactions are well recognized including increased rates of infections, lupus-like disease and demyelinating lesions. Progressive multifocal leukoencephalopathy (PML) is a rare but severe demyelinating disease caused by the...

Background Anti-TNF agents have been a cornerstone of IBD therapy; however, response to treatment has been variable, and clinically applicable biomarkers are urgently needed. We hypothesized that the type I and type II interferon (IFN) signatures may be a confounding factor for response to antitumor necrosis factor (TNF) treatment via interactions...

Respiratory complaints alone or in association with musculoskeletal complaints can be the predominant presenting feature of antisynthetase syndrome. Therefore, antibodies to cellular antigens should be evaluated in such clinical settings. Respiratory complaints alone or in association with musculoskeletal complaints can be the predominant presentin...

Objective To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV. Methods From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and f...

Objectives: The objective of this work is to present a Training Tool designed to support healthcare professionals involved in the diagnosis and management of Sjögren's syndrome. Methods: The Training Tool aims to fulfil the gap of targeted education by providing a structured protocol of training including state of the art guidelines and practice...

The recent approval of Immunologic checkpoint inhibitors as an effective therapeutic strategy against cancer came at the cost of toxicities mediated by an excessive activation of immune system against health tissues, including among others musculoskeletal and sicca complaints.The latter occur in the context of an entity reminiscent of Sjogren's syn...

Background Sjögren’s syndrome (SS) affects mainly individuals of the 4 th or 5 th decade of life, although patients with early (≤35 years old) or late (≥65 years old) disease onset have been described in the literature. The clinical spectrum of the disease extends from mild dryness to severe systemic vasculitis and lymphoproliferative disorders. Th...

Background Sjögren’s syndrome (SS) is characterized by B cell hyperactivity reflected by hypergammaglobulinemia as well as a plethora of autoantibodies including antinuclear antibodies (ANA), anti-Ro/SSA, anti-La/SSB and rheumatoid factors (RF). Previous studies have focused on the phenotype of single positive (ANA or anti-Ro/SSA or anti-La/SSB) or...

Background Sjögren’s syndrome (SS) is characterized by the presence of lymphocytic infiltration around the ductal epithelium of the salivary and lachrymal glands. The periepithelial inflammatory lesions and the enclosed B cell component are responsible for the glandular and extraglandular manifestations of the disease. Previous studies have shown t...

Background Interleukin-1 (IL-1) is a major mediator of the inflammatory cascade in Still’s disease and an established therapeutic target. Objectives To assess the efficacy and safety of the IL-1b inhibitor canakinumab in adolescent and adult patients with refractory Still’s disease. Methods We conducted a retrospective longitudinal outcome study...

Background Cryoglobulinemic vasculitis (CV) is a serious complication of Sjögren’s syndrome (SS) and is closely associated with type II IgMk cryoglobulins. CV has been well documented in HCV patients without SS, and shares common features with CV in SS. So far, few studies have described the clinical picture of CV in HCV negative SS, but the number...

Purpose of review Sjögren’s syndrome (SS) is a chronic systemic disorder of autoimmune origin characterized by impaired secretory function of the exocrine glands and a high susceptibility for non-Hodgkin’s lymphoma development. The aim of the present review is to summarize the main clinical and molecular contributors of lymphoma development in the...

We read with interest the article ‘’Myositis Autoantibodies: A Comparison of Results from the Oklahoma Medical Research Foundation Myositis Panel to the Euroimmun Research Line Blot’’ by Mecoli et al.1. The study showed that, by using the Euroimmun panel for myositis‐specific autoantibodies (MSA), different cut‐offs should apply for all specificiti...

Lymphoma development constitutes one of the most serious clinico-pathological manifestations of patients with Sjögren's Syndrome (SS). Over the last decades the risk for lymphomagenesis in SS patients has been studied aiming to identify novel biomarkers and risk factors predicting lymphoma development in this patient population. Objective: The curr...

Sjögren’s syndrome (SS) is a chronic autoimmune disease of slow progression, with a prevalence of approximately 0.5% in the general population. It mainly affects the exocrine glands of middle-aged women, with the ratio of female to male patients being 9:1. Functional epithelium is gradually affected by lymphocytic infiltrates, resulting in decrease...

Atherosclerosis has long been considered as a lipid storage disease. Recent data suggest that autoimmune mechanisms seem to be involved in the pathophysiology of atherosclerosis. The presence of activated endothelial vascular cells, neutrophils, macrophages, T- and to a lesser extent B-cells in atherosclerotic plaques, together with the proinflamma...

Sjögren's syndrome (SS) is a prototype autoimmune disease characterized by oral and ocular mucosal dryness following chronic inflammation of salivary and lachrymal glands, respectively. Profound B cell hyperactivity along with systemic manifestations including fatigue, musculoskeletal complaints, features related to hepatic, pulmonary, renal and ne...

Recent data suggest an important role of type I interferons (IFN) in antiphospholipid syndrome (APS). Here we aimed to evaluate the interplay of type I and type III (or IFNλs) IFNs in APS and potential clinical and serological associations. Our findings suggest that patients with primary APS (PAPS) and systemic lupus erythematosus (SLE)/APS display...

We were delighted to read the letter by Killian, et al , which challenges the use of the terms primary and secondary human Sjögren syndrome (SS) even in experimental animal models of SS ¹ . These terms were coined almost 40 years ago on the basis of a study that revealed clinical, immunologic, and genetic differences among patients expressing sicca...

Hypertension is a multifactorial disorder with serious complications and unknown etiology. Among potential contributors, immune dysregulation has been also proposed. The study population included 61 consecutive hypertensive patients and 55 healthy individuals of similar age and sex distribution. All study participants underwent a thorough evaluatio...

Comorbidities including subclinical atherosclerosis, neuropsychological aberrations and lymphoproliferation represent a major burden among patients with systemic autoimmune diseases; they occur either as a result of intrinsic disease related characteristics including therapeutic interventions or traditional risk factors similar to those observed in...

Genetic variants of the three-prime repair exonuclease 1 (TREX1) -an exonuclease involved in DNA repair and degradation- have been previously found to increase susceptibility to Aicardi Goutieres syndrome, familial chilblain lupus and systemic lupus erythematosus. We aimed to explore whether TREX1 common variants could influence the risk of primary...

Background One of the major complications of primary Sjogren’s syndrome (SS) is the development of B-cell non-Hodgkin’s lymphoma (B-NHL). The contribution of tissue macrophages in the pathogenesis of B-NHL, based on previous histopathological studies, appears to be significant. Extracellular lipoprotein-associated phospholipase A2 (Lp-PLA2) is a pr...

Background Growing evidence supports a link between alterations in bone metabolism and cardiovascular (CV) disease in both general and autoimmune populations. Objectives In the current study we aimed to explore whether vitamin D deficiency and/or increased parathormone (PTH) levels, as well as impairment of bone mass density, influence CV risk in...

Background Activation of type I and II interferon (IFN) pathways contributes to the pathogenesis of systemic autoimmune diseases. We have previously shown increased expression of the LINE-1 (L1) endogenous retrotransposon in systemic lupus erythematosus (SLE) kidneys and in minor salivary glands (MSG) from primary Sjögren’s syndrome patients (SS) t...

Background Primary Sjögren’s Syndrome (SS) is a systemic autoimmune disease, characterized by increased risk of non-Hodgkin’s lymphoma development. A functional polymorphism of the immunoreceptor LILRA3 (Leukocyte immunoglobulin-like receptor A3) has been recently identified as a potential etiopathogenic factor for both pSS susceptibility and lymph...

Background Primary Sjögren’s Syndrome (pSS) is a chronic systemic autoimmune disease with diverse clinical picture, extending from exocrinopathy to systemic disease and non-Hodgkin’s lymphoma (NHL). Usually, it affects middle aged women, but early disease onset (≤35 years old) has been also observed. So far, there is a limited number of studies to...

Background Primary Sjögren’s Syndrome (SS) is characterized by B lymphocyte hyperactivity with B cell activating factor (BAFF) acting as an important regulator. Single Nucleotide Polymorphisms (SNPs) of the BAFF gene have been implicated in the pathogenesis of several autoimmune diseases including lupus and SS both of which are characterized by hei...

Background Primary Sjogren’s syndrome (SS) is an autoimmune exocrinopathy characterized by chronic salivary and lacrimal glands dysfunction. Recent studies suggest that activation of the receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK and osteoprotegerin (OPG) pathway is implicated in the development of autoimmunity. Objectives Th...

Type I interferons (IFN) have long been recognised as mediators of innate immune defense mechanisms against viral threats. Robust evidence over the last 15 years revealed their significant role in the pathogenesis of systemic autoimmune diseases, including systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Despite the progress, methods...

In primary SS (pSS), chemokines and cytokines orchestrate immunopathology driven by a complex network of interacting inflammatory cells. In recent years, the importance of chemotactic and non-chemotactic cytokines that control function, movement and placing of all cells within the inflamed exocrine glands and directing immunopathology has become in...