Adrianos Nezos

CD40/CD40L signaling and its implication in health and disease.

CD40, a transmembrane receptor of the tumor necrosis factor gene superfamily is expressed on a variety of cells, such as monocytes, B‐cells, antigen presenting cells, endothelial, smooth muscle cells, and fibroblasts. The interaction between CD40 and CD40 ligand (CD40L) enhances the expression of cytokines, chemokines, matrix metalloproteinases, growth factors, and adhesion molecules, mainly through the stimulation of nuclear factor kappa B. The aim of this review is to summarize the molecular and cellular characteristics of CD40 and CD40L, the mechanisms that regulate their expression, the cellular responses they stimulate and finally their implication in the pathophysiology of inflammatory and autoimmune diseases.

Type I and II interferon signatures in Sjogren's syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjogren's related lymphomagenesis

Both type I and II interferons (IFNs) have been implicated in the pathogenesis of Sjogrens syndrome (SS). We aimed to explore the contribution of type I and II IFN signatures in the generation of distinct SS clinical phenotypes including lymphoma development. Peripheral blood (PB) from SS patients (n = 31), SS patients complicated by lymphoma (n = 13) and healthy controls (HC, n = 30) were subjected to real-time PCR for 3 interferon inducible genes (IFIGs) preferentially induced by type I IFN, 2 IFIGs preferentially induced by IFNγ as well as for IFNα and IFNγ genes. The same analysis was performed in minor salivary gland tissues (MSG) derived from 31 SS patients, 10 SS-lymphoma patients and 17 sicca controls (SC). In PB and MSG tissues, overexpression of both type I and type II IFIGs was observed in SS patients versus HC and SC, respectively, with a predominance of type I IFN signature in PB and a type II IFN signature in MSG tissues. In SS-lymphoma MSG tissues, lower IFNα, but higher IFNγ and type II IFIG transcripts compared to both SS and SC were observed. In receiver operating characteristic curve analysis, IFNγ/IFNα mRNA ratio in MSG tissues showed the best discrimination for lymphoma development. Discrete expression patterns of type I and II IFN signatures might be related to distinct SS clinical phenotypes. Additionally, IFNγ/IFNα mRNA ratio in diagnostic salivary gland biopsies is proposed as a novel histopathological biomarker for the prediction of in situ lymphoma development in the setting of SS.

Expression of Long Interspersed Nuclear Element 1 Retroelements and Induction of Type I Interferon in Patients With Systemic Autoimmune Disease

Increased expression of type I interferon (IFN) and a broad signature of type I IFN–induced gene transcripts are observed in patients with systemic lupus erythematosus (SLE) and other systemic autoimmune diseases. To identify disease‐relevant triggers of the type I IFN pathway, this study sought to investigate whether endogenous virus‐like genomic repeat elements, normally silent, are expressed in patients with systemic autoimmune disease, and whether these retroelements could activate an innate immune response and induce type I IFN.

Long interspersed nuclear element‐1 retroelements are expressed in patients with systemic autoimmune disease and induce type I interferon

Increased expression of type I interferon (IFN) and a broad signature of type I IFN–induced gene transcripts are observed in patients with systemic lupus erythematosus (SLE) and other systemic autoimmune diseases. To identify disease‐relevant triggers of the type I IFN pathway, this study sought to investigate whether endogenous virus‐like genomic repeat elements, normally silent, are expressed in patients with systemic autoimmune disease, and whether these retroelements could activate an innate immune response and induce type I IFN.

Preferential expression of IGF-1Ec (MGF) transcript in cancerous tissues of human prostate: evidence for a novel and autonomous growth factor activity of MGF E peptide in human prostate cancer cells.

By alternative splicing the IGF‐1 gene produces several different transcripts, including IGF‐1Ec (MGF). The latter has been mainly associated with muscle regeneration processes.

New advances in the classification, pathogenesis and treatment of Sjogren's syndrome.

Purpose of reviewIn the current review, we summarize the newly proposed classification criteria for Sjogrens syndrome, recent findings of Sjogrens syndrome pathogenesis and the latest achievements in disease management. Recent findingsA new set of Sjogrens syndrome classification criteria has been recently proposed by an expert consensus panel of the American College of Rheumatology–Sjögrens International Collaborative Clinical Alliance. Recent findings reveal new aspects in the activation of innate and adaptive immune pathways and novel animal models – highly reminiscent of human Sjogrens syndrome–are described. Of particular note, apoptosis of epithelial cells as a result of deficient I&kgr;B&zgr;, previously shown to be a modulator of NF&kgr;B activity, has been suggested as a central pathogenetic event. Mechanistic data on anti-B-cell therapies, gene transfer approaches aimed to restore secretory function, as well mesenchymal stem cell transplantation in mice and humans are also discussed. SummaryOver the last year, a new set of classification criteria for Sjogrens syndrome has been suggested, new Sjogrens syndrome-like animal models have been described and significant progress has been made in understanding the activation of innate and adaptive immune responses. New therapeutic approaches have been also implemented with variable success.

Molecular markers detecting circulating melanoma cells by reverse transcription polymerase chain reaction: methodological pitfalls and clinical relevance

Abstract Herein, we expound the theory of circulating melanoma cells (CMCs) and their detection with reverse transcription polymerase chain reaction as a molecular staging approach. We discuss the molecular markers that have been used for CMC detection focusing on the use of these markers for multiplex detection analysis. Finally, we comment on the contradictory data of CMC detection studies in the literature and we propose possible solutions which may contribute to the clinical significance of CMC detection in patient management. Clin Chem Lab Med 2009;47:1–11.

Detection of circulating tumor cells in bladder cancer patients

The methods employed for the detection of circulating bladder cancer cells (CBCs) and their use as a molecular staging tool in clinical settings are thoroughly reviewed. CBC isolation and enrichment methods are discussed according to their advantages and pitfalls along with the clinical data of PCR-based techniques used for CBC detection. In addition, we review the specificity of molecular markers that have been proposed so far for CBC identification, and we comment on the controversial clinical data, proposing laboratory approaches which may improve the clinical significance of CBC detection in bladder cancer.

Detection of the circulating tumor cells in cancer patients

As the presence of tumor cells circulating in the blood is associated with systemic disease and shortened survival, the establishment of a method to detect circulating tumor cells (CTCs) is of critical importance for a more concise staging and follow-up of cancer patients. Recently, the most robust strategies for the determination of CTCs are the PCR-based methods and the CellSearch® system that exploits the immunofluorescent characterization and isolation of cancer cells. Herein, we analyzed the experimental strategies used for determining CTCs with respect to accuracy, sensitivity and reproducibility in cancers of the breast, colon, prostate and melanoma.

Fatigue in Primary Sjögren's Syndrome: Clinical, Laboratory, Psychometric, and Biologic Associations.

To identify independent contributors of fatigue in primary Sjögrens syndrome (SS) patients, taking into account clinical, laboratory, and psychological features, and to explore the potential role of interferon (IFN)–induced gene indoleamine 2,3‐dioxygenase (IDO‐1), anti–21‐hydroxylase (anti‐21[OH]) antibodies, and soluble BAFF.