Tailoring the treatment of inflammatory rheumatic diseases by a better stratification and characterization of the clinical patient heterogeneity. Findings from a systematic literature review and experts' consensus.

Inflammatory rheumatic diseases are different pathologic conditions associated with a deregulated immune response, codified along a spectrum of disorders, with autoinflammatory and autoimmune diseases as two-end phenotypes of this continuum. Despite pathogenic differences, inflammatory rheumatic diseases are commonly managed with a limited number of immunosuppressive drugs, sometimes with partial evidence or transferring physicians' knowledge in different patients. In addition, several randomized clinical trials, enrolling these patients, did not meet the primary pre-established outcomes and these findings could be linked to the underlying molecular diversities along the spectrum of inflammatory rheumatic disorders.

Postgenomic Bioinformatic Analysis of Nucleic Acid Sequences Expressed in the Salivary Gland Epithelial Cells of Primary Sjögren's Syndrome Patients in Search of Microorganisms and Endogenous Retroviruses.

Several previous studies from our laboratory have indicated that the salivary gland epithelia of primary Sjögren's syndrome (SS) patients are not only the target of autoimmune immune responses, but also key instigators of the chronic salivary gland inflammatory infiltrates of patients. In particular, the comparative analysis of salivary gland tissue specimens and of in-vitro cultured non-neoplastic salivary gland epithelial cell lines (SGEC, of ductal type) from SS-patients and non-SS disease-controls, have unequivocally highlighted the presence of intrinsic activation in the ductal epithelia of SS-patients and of aberrant expression of inflammagenic molecules thereof, that correlate with the severity of local histopathologic changes, as well as of systemic manifestations of the disease. In the same context, we have recently shown that the ductal epithelia of SS-patients manifest cell-autonomous activation of the AIM2 inflammasome owing to the presence of aberrant cytoplasmic accumulations of damaged DNA.

Idiopathic retroperitoneal fibrosis: clinical features, treatment modalities, relapse rate in Greek patients and a review of the literature.

Objectives: Retroperitoneal fibrosis (RPF) is mostly idiopathic (iRPF); however, it can be secondary to drugs, malignancies, infections, or, as recently recognised, can be part of the IgG4-related diseases. The aim of our study was i) to describe the presenting clinical/laboratory/imaging features and treatment modalities used in patients with iRPF and ii) to evaluate factors potentially associated with disease relapse.

Methods: The medical records of patients diagnosed with iRPF and followed in four tertiary medical units in Athens, Greece from 2000 to 2018 were retrospectively evaluated.

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

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.

Cell-autonomous epithelial activation of AIM2 (absent in melanoma-2) inflammasome by cytoplasmic DNA accumulations in primary Sjögren's syndrome.

Primary Sjögren's syndrome (SS) is characterized by chronic periductal inflammatory infiltrates in the salivary glands. Several previous studies have indicated that the ductal epithelia of SS patients play a pro-inflammatory role and manifest an intrinsically activated status, as demonstrated in cultured non-neoplastic ductal salivary gland epithelial cell (SGEC) lines. Herein, we investigated the activation of inflammasomes in the salivary epithelia of SS patients and non-SS controls, using salivary biopsy tissues and SGEC lines.

Perturbation of transcriptome in non-neoplastic salivary gland epithelial cell lines derived from patients with primary Sjögren's syndrome.

The data presented here are related to the research article titled " (Vakrakou et al., Journal of Autoimmunity, in press, 2017). In the cited manuscript, using comparative analyses of salivary gland biopsy specimens and ductal salivary gland epithelial cell (SGEC) lines from SS patients and disease controls, we have demonstrated that the ductal epithelia of SS patients display constitutively reduced PPARγ expression, transcriptional activity and anti-inflammatory function that were associated with cell-autonomously activated NF-κB and IL-1β pathways in these cells.

Systemic activation of NLRP3 inflammasome in patients with severe primary Sjögren's syndrome fueled by inflammagenic DNA accumulations.

Sjögren's syndrome (SS) patients manifest high cell-free DNA (cf-DNA) levels in serum, associated with impaired DNaseI activity. Undegraded DNA may accumulate in tissues and act as an inflammasome-activating signal. Herein, we investigated the occurrence of aberrant DNA build-up in various biologic compartments of SS patients and its correlation with the activity of NLRP3 and AIM2 inflammasomes.

Impaired anti-inflammatory activity of PPARγ in the salivary epithelia of Sjögren's syndrome patients imposed by intrinsic NF-κB activation.

Sjögren's syndrome (SS) patients manifest inflammation in the salivary glands (SG) and evidence of persistent intrinsic activation of ductal SG epithelial cells (SGEC), demonstrable in non-neoplastic SGEC lines derived from patients (SS-SGEC). The peroxisome-proliferator-activated receptor-γ (PPARγ) mediates important anti-inflammatory activities in epithelial cells. Herein, the comparative analysis of SG biopsies and SGEC lines obtained from SS patients and controls had revealed constitutively reduced PPARγ expression, transcriptional activity and anti-inflammatory function in the ductal epithelia of SS patients that were associated with cell-autonomously activated NF-κB and IL-1β pathways.

Biologic treatment for rheumatic disease: real-world big data analysis from the Greek country-wide prescription database.

Objectives: To directly assess the prevalence of inflammatory rheumatic disease under treatment with biologic disease modifying anti-rheumatic drugs (b-DMARDs) and compare treatment patterns between rheumatoid arthritis (RA) and spondyloarthropathy (SpA), including psoriatic arthritis.

Methods: The obligatory country-wide prescription electronic database covering 10.223.

Decreased serum DNase1-activity in patients with autoimmune liver diseases.

Deoxyribonuclease1 (DNase1) is involved in chromatin degradation of apoptotic cells. Its deficiency results in accumulation of self-DNA, which in turn may induce inflammation and autoimmunity. We assessed for the first time serum DNase1-activity in a large consecutive cohort of treatment-naïve patients with autoimmune liver diseases (ALD).

Treat-to-target biologic therapy in patients with rheumatoid arthritis is more efficacious and safe compared to delayed initiation of biologics: a real-world study.

Objectives: Rheumatoid arthritis (RA) is a chronic, devastating disease. Treat-to-target strategy (T2T) more than the usual care, reduces disease activity by using aggressively all therapeutic options. The aim of the study was to evaluate our hypothesis that T2T strategy using biologic disease-modifying anti-rheumatic drugs (bDMARDs), when needed, is also safer than the usual care characterised by delayed initiation of bDMARDs.

Adverse events and infections in patients with rheumatoid arthritis treated with conventional drugs or biologic agents: a real world study.

Objectives: Treatment of rheumatoid arthritis (RA) with disease-modifying anti-rheumatic drugs (DMARDs), either synthetic (sDMARDs) or biologic agents (bDMARDs) has significantly improved disease outcome. However, the impact of therapy-related adverse events (AEs), mild, moderate or serious, on disease outcome is under debate. The purpose of the study was to test the hypothesis that AEs, including infections, are rather common in patients receiving bDMARDs than in those receiving sDMARDs.

Asymptomatic bacteriuria in women with autoimmune rheumatic disease: prevalence, risk factors, and clinical significance.

Background: Data regarding the prevalence and clinical significance of asymptomatic bacteriuria (AB) in women with autoimmune rheumatic disease (ARD) are scarce.

Methods: In this prospective, case-control study, consecutive female outpatients with ARD were screened for AB. For each patient, demographics, type, duration, and treatment of underlying ARD, and risk factors for urinary tract infection (UTI), were recorded.

Impaired clearance of early apoptotic cells mediated by inhibitory IgG antibodies in patients with primary Sjögren's syndrome.

Objectives: Deficient efferocytosis (i.e. phagocytic clearance of apoptotic cells) has been frequently reported in systemic lupus erythematosus (SLE).

Impaired degradation and aberrant phagocytosis of necrotic cell debris in the peripheral blood of patients with primary Sjögren's syndrome.

Aberrant removal of necrotic debris is considered a feature with inflammatory consequences in SLE. Herein, primary Sjögren's syndrome (SS) patients were investigated for the first time for the capacity of their sera to degrade secondary necrotic cell remnants (SNEC) and DNA (endonuclease DNase1 activity), as well as for uptake of SNEC by blood-borne phagocytes. For comparison, specimens from unselected SLE and RA patients and from healthy blood donors (HBD) were also studied.

Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti-Ro52 antibodies in patients with autoimmune hepatitis.

Background & Aims: Antibodies (Abs) to soluble liver antigen/liver pancreas (anti-SLA/LP) are considered markers of worse prognosis and outcome in patients with autoimmune hepatitis (AIH) although this assumption has recently been attributed to their frequent co-expression with Abs against Ro52 (anti-Ro52). To assess the clinical significance of anti-SLA/LP Abs alone or in combination with anti-Ro52 in AIH patients and determine the immunodominant Ro52 epitopes according to the anti-SLA/LP status.

Methods: Twenty-three anti-SLA/LP-positive and 106 anti-SLA/LP-negative AIH patients were included.

A monoterpene, unique component of thyme honeys, induces apoptosis in prostate cancer cells via inhibition of NF-κB activity and IL-6 secretion.

We have previously demonstrated that Greek thyme honey inhibits significantly the cell viability of human prostate cancer cells. Herein, 15 thyme honey samples from several regions of Greece were submitted to phytochemical analysis for the isolation, identification and determination (through modern spectral means) of the unique thyme honey monoterpene, the compound trihydroxy ketone E-4-(1,2,4-trihydroxy-2,6,6-trimethylcyclohexyl)-but-3-en-2-one. We investigated the anti-growth and apoptotic effects of the trihydroxy ketone on PC-3 human androgen independent prostate cancer cells using MTT assay and Annexin V-FITC respectively.

Phenotypical analysis of lymphocytes with suppressive and regulatory properties (Tregs) and NK cells in the papillary carcinoma of thyroid.

Context: The immune system seems to play a key role in preventing metastasis and recurrence of thyroid cancer. T regulatory lymphocytes (Tregs) and natural killer (NK) cells play an important role in the dysfunction of the host immune system in cancer patients.

Objective: We investigated thyroid gland infiltration by Tregs and NK cells in patients with papillary thyroid cancer (PTC) and thyroid nodular goiter (TNG).

The salivary gland epithelial cells of patients with primary Sjögren's syndrome manifest significantly reduced responsiveness to 17β-estradiol.

Several lines of evidence indicate that salivary gland epithelial cells (SGEC) play an important role in the pathogenesis of primary Sjogren's syndrome (SS). Normal SGEC have been shown to possess functional estrogen receptors, however, the estrogenic response of SGEC in patients with SS has not been previously assessed. To address this issue, we comparatively tested cultured non-neoplastic SGEC lines from SS patients (SS-SGEC, n = 8) and from disease controls (control-SGEC, n = 12) in a standard estrogenic inhibition assay of cytokine-induced adhesion molecule expression, where the modulation of the expression of constitutive and interferon-gamma (IFNγ)-induced CD54/ICAM.

Cellular microRNAs (miRNAs) and Sjögren's syndrome: candidate regulators of autoimmune response and autoantigen expression.

MicroRNAs (miRNAs) are small non-coding RNA molecules that suppress gene expression at post-transcriptional level. miRNAs are considered as fine-tuning regulators of diverse biological processes, including the development and function of the immune system. Emerging data have implicated the deregulated expression of certain miRNAs or miRNA networks in the pathogenesis of autoimmune diseases.

Coronary artery abnormalities in CREST syndrome revealed by cardiovascular magnetic resonance imaging.

CREST syndrome represents a subset of systemic sclerosis (SSc). Five patients with CREST syndrome and 5 with SSc without cardiac symptoms and with normal routine cardiac examination were investigated by cardiovascular magnetic resonance. All CREST patients had ectatic coronary arteries, and in 1 of them, an inferior, transmural myocardial infarction was identified.