Research

In recent years, our research group has been actively involved in elucidating the distinct clinical phenotypes of Sjogren's disease and advancing our understanding of its underlying pathogenesis. Specifically, our research endeavors have included:

We systematically determined the clinical phenotypes within various subgroups of patients diagnosed with Sjogren's syndrome. This included investigations into male patients, those with a negative autoantibody test, individuals manifesting initial symptoms before the age of <35 and after the age of 65, patients presenting with a severe histological picture (Focus score >4), and those diagnosed with cryoglobulinemic vasculitis. These determinations were based on harmonized data derived from 700 patients across diverse Sjogren's centers in Europe, participating in the European HarmonicSS project, of which our group served as coordinators.

Our research group conducted a thorough examination of the survival rates of patients with lymphoma associated with Sjogren's syndrome. Utilizing retrospective data from our extensive cohort, which comprises the majority of patients with SS-related lymphoma worldwide, we provided, for the first time, a documented 10-year survival analysis for these patients.

We conducted a comprehensive study on the differential expression of cytokines in a substantial number of patients with Sjogren's syndrome, covering the entire spectrum of clinical heterogeneity in the disease, alongside healthy controls. The Luminex technique facilitated the simultaneous and multiple detection of cytokines, contributing valuable insights into the immunological aspects of the disease.

Our research utilizes Image Mass Cytometry (IMC) through the Hyperion platform, an innovative and highly precise method enabling multi-parametric analysis of tissue sections while preserving intact spatial architecture. We employ this advanced technology to analyze biopsies from patients with Sjogren's Syndrome (SS) exhibiting mild, moderate, and severe infiltration, as well as biopsies from patients with SS-associated lymphoma. Our investigation of cell subpopulations in these patients has revealed the presence of a double-negative B cell population (CD27-, IgD-, CD20+, CD45RB+) within the tissue of patients with severe infiltrates or lymphoma. This finding underscores the significance of this particular subpopulation in the progression of lymphomatogenesis in Sjogren's Syndrome. In collaboration with the Director/Researcher of IIBEAA, Dr. E. Andreakos, we are poised to extend our study of this novel cell subpopulation into experimental models, seeking a deeper understanding of its role in the context of Sjogren's Syndrome and associated lymphoma pathogenesis.

These multifaceted research initiatives collectively enhance our understanding of Sjogren's disease across clinical, survival, and immunological dimensions.

In recent years, our research group has been actively engaged in advancing the understanding of the pathogenesis of giant cell arteritis (GCA), employing serial samples obtained from patients at two distinct time points during exacerbation and remission phases of the disease.

Specifically, our investigations have yielded the following key findings:

Our study focused on elucidating the role of neutrophil extracellular traps (NETs) in the inflammatory response of GCA. We determined the localization of NETs in temporal artery biopsies, revealing a spatial affinity with the vasa vasorum in the outer layer of the affected vessel (adventitia). Immunohistochemical analysis highlighted the co-expression of pro-inflammatory cytokines IL-6 and IL-17 within the structures of NETs, emphasizing their crucial pro-inflammatory and/or immunoregulatory role.

We conducted a comprehensive analysis of the metabolomic signature in GCA patients, identifying specific metabolites capable of distinguishing the active from the inactive phase of the disease. These metabolites not only reflect the dynamic kinetics of the disease over time but also serve as biomarkers for both treatment response and the potential emergence of side effects, offering valuable information for treating physicians. In collaboration with IBEAA Director/Researcher E. Andreakos, our ongoing research involves the study of small lipids implicated in inflammation and its resolution.

In collaboration with the research group of Professor B. Gorgoulis, our studies have delved into cellular senescence in patients with GCA. Notably, fibroblast populations from temporal arteries of GCA patients exhibit a cellular senescence phenotype, characterized by prolonged proinflammatory cytokine secretion (SASP phenotype), potentially contributing to both the initiation and perpetuation of inflammation. To conduct these studies, we have established robust protocols, including immunofluorescence and immunohistochemistry of paraffin tissues for co-localization of aging and inflammatory markers, an artery tissue culture model for studying the microenvironment of inflammation, and the utilization of classical molecular biology protocols and modern transcriptome analysis methods in collaboration with the laboratory of Academician D. Thanos at IIBEAA.

In partnership with Mr. Anagnostopoulos at IIBEAA, we employ PET-SCAN with 18F-fluorodeoxyglucose (FDG) to investigate the uptake of 18F-FDG within the vascular wall, aiming to establish connections between the extent, intensity, and localization of inflammation with soluble inflammatory mediators (cytokines). This innovative approach enhances our understanding of the dynamic interplay between inflammation and its molecular mediators in the context of GCA.