Athanasios G. Tzioufas

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, with key features being synovial hyperplasia, autoantibody production, and ultimately cartilage and bone destruction. The pathogenesis of rheumatoid arthritis (RA) is not fully understood, but it is estimated that genetic factors account for 50–60% of the risk, with the remainder attributed to environmental factors, including infectious agents, smoking, gut microbiota, and diet. Given that most current clinical trials on RA and nutrition are limited in sample size and duration, there is an unmet need for higher-quality studies in the future, a need that EULAR has already recognized. Objective: This article aims to investigate the impact of diet and nutritional factors on the development, progression, and potential prevention of RA. Specifically, it provides a comprehensive review of certain foods, such as alcohol, gluten, red meat, and saturated and trans fats, and their contribution to the onset and progression of rheumatoid arthritis (RA). In addition, it examines the effect of key anti-inflammatory nutrients in reducing the risk of RA, including olive oil, fatty fish, juices, and certain fruits. Finally, it discusses the potential protective effects of certain dietary patterns, such as the Mediterranean diet (MD) and diets rich in omega-3 polyunsaturated fatty acids (PUFAs). Methods: A comprehensive literature search was conducted in the PubMed/Medline, Science Direct, and Scopus databases (1990–2025). English-language observational studies, clinical trials, and systematic reviews addressing the relationship between diet and dietary patterns and RA were included. Results: High consumption of red and processed meat, saturated and trans fats, sugary drinks, and gluten (in vulnerable individuals) is associated with increased RA risk and greater disease activity, partly through pro-inflammatory pathways and gut dysbiosis. In contrast, regular intake of olive oil, fatty fish rich in omega-3 polyunsaturated fatty acids, fruit juices, cocoa, certain fruits, and vitamin D appears protective and may reduce disease activity and symptom severity. Adherence to anti-inflammatory dietary patterns, particularly the Mediterranean diet and diets rich in omega-3 fatty acids, is consistently associated with a lower incidence of RA, reduced inflammatory markers, and improved clinical outcomes. However, most available studies are limited by small sample sizes, short duration, heterogeneous methodologies, and potential confounding by other lifestyle factors (e.g., smoking, obesity). Conclusions: Although an appropriate diet and dietary habits cannot replace pharmacological therapy, current knowledge supports the inclusion of an anti-inflammatory diet as an adjunct strategy in the prevention and management of RA. The relatively limited studies that have been conducted suggest that high-quality, large-scale, prospective studies are needed to prevent and treat RA. These studies should incorporate genetic, microbiome, and long-term clinical endpoints, so as to establish definitive dietary recommendations and allow for personalized nutritional interventions for patients with RA.

To investigate the effect of treatment in a series of patients with Sjögren's disease (SjD) associated interstitial lung disease (ILD). Twenty-four primary SjD-ILD patients, followed-up from October 2022 to June 2025 were included in the study. Based on clinical judgement, 12 received treatment for ILD, while 12 did not, following a "watch-and-wait" policy. Participants were evaluated in 2 time points with an interval of 24±6 months. ILD was diagnosed by HRCT according to Fleischner Society definitions, performed at baseline due to respiratory symptoms and/or abnormal pulmonary function tests. Spirometry and diffusing capacity for carbon monoxide (DLCO) were performed at both visits. Progression of ILD was defined as absolute decline of predicted forced vital capacity (FVC) ≥5%. The treatment regimens of 12 SjD-ILD patients who received treatment included rituximab, mycophenolate mofetil, azathioprine and tocilizumab. The treated group displayed higher extent of ILD on HRCT at baseline visit (median: 20% vs. 10%, p=0.006), more frequently findings of small airways disease on HRCT (58% vs. 8%, p=0.027) and tended to present lower FVC (mean: 81.3% vs. 96.7%, p=0.086) compared to the untreated. FVC and DLCO remained stable between baseline and follow-up visit in both groups. However, the change in DLCO between the two visits was worse in the treated than untreated patients (mean: -11.2% vs. 4.8%, p=0.003). The number of SjD-ILD patients presenting progression of ILD did not differ between the two groups (25% vs. 33%, p=0.999). SjD-ILD clinical course is variable, with the most aggressive form to be controlled by immunosuppressive treatment.

Nomenclature for the disease widely known as Sjögren syndrome has proven unsatisfactory. Patients have perceived ‘syndrome’ as indicative of a vague collection of symptoms, prompting the Sjögren’s Foundation to abandon the term. Furthermore, the traditional distinction between ‘primary’ and ‘secondary’ forms fails to account for the complex interplay between overlapping autoimmune diseases. Following a bibliometric analysis, systematic literature review and a Delphi consensus process with equal involvement of professional and patient representatives, five recommendations are now issued. First, the term ‘Sjögren disease’ should replace ‘Sjögren syndrome’. Second, the acronym ‘SjD’ should be used as an abbreviation for ‘Sjögren disease’. Third, the descriptor ‘associated’ should be used in lieu of ‘secondary’ for Sjögren disease occurring in association with a second systemic autoimmune disease for which classification criteria are fulfilled. Fourth, Sjögren disease is the preferred terminology in common parlance and in clinical diagnosis, without differentiation as to primary and associated forms. Fifth, the differentiation between primary and associated Sjögren is recommended for scientific studies to define a homogeneous population. In conclusion, the consensus endorses ‘Sjögren disease’ as the official nomenclature to acknowledge the distinct pathogenesis of this disorder and to improve clarity in both clinical practice and research.

Introduction: Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are autoimmune/autoinflammatory disorders presenting as acute inflammatory responses and are highly responsive to steroids. In this report, we aim to decipher the immune landscape including immune cell subpopulations, plasma cytokines, and small lipid mediators (LMs) at the very early stages of steroid treatment initiation in 4 distinct time points at: 0h (T1), 48h (T2), 96h (T3), and 24 weeks (T4).Patients and methods: Serum, plasma and peripheral blood mononuclear cells (PBMCs) were collected prospectively from 8 GCA and 6 PMR newly diagnosed patients. Sixteen healthy individuals served as controls (HC). Deep immunophenotyping by CyTOF was performed in PBMCs at T1-T3. A multiplex Luminex assay measured serum levels of 21 cytokines at T1 and T3. Levels of lipid mediators (LMs) were evaluated at T1, T3 and T4 with the LC-MS/MS method.Results: Total CD8+ T cells and DCs were decreased within 48–96 hours, following steroid treatment, while B-cells were increased at 48 hours. Further analysis of immune subpopulations containing the major cell types revealed different frequencies of distinct CD8+, CD4+, DCs, and B cell subtypes. Out of 21 cytokines/chemokines evaluated, only ITAC levels were decreased at T3. The ratio of pro/anti-inflammatory LMs was high at T1 in patients with either PMR or GCA. However, 6 months after steroid treatment it returned to normal in PMR patients, but remained high in GCA patients, providing the only discriminatory element between the two diseases.Conclusion: The rapid clinical improvement of GCA and PMR patients, following steroid treatment, is associated with immune cell type alterations, but it is poorly associated with plasma cytokine levels. Small lipid mediators can differentiate GCA and PMR patients. The persistently elevated levels of pro-inflammatory LMs might be related to the underlying residual tissue inflammation described in GCA. These preliminary results suggest that further studies in a larger patient cohort are required to validate these findings.

Giant cell arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial GCA and large-vessel vasculitis (LV)-GCA, involving the thoracic aorta and its branches. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosing patients with systemic disease. However, its association with soluble inflammatory markers is still elusive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT-positive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The most-diseased-segment target-to-background ratio (TBR_MDS) was calculated for 13 LV-GCA patients, while 14 cranial GCA and 14 Polymyalgia Rheumatica patients with negative initial PET/CT scans served as disease controls. Serum macrophage-related cytokines were evaluated by cytometric bead array (CBA). Finally, previously published NMR/metabolomics data acquired from the same blood sampling were analyzed along with PET/CT findings. TBR_MDS was significantly increased in active versus inactive disease (3.32 vs. 2.65, p = 0.006). The analysis identified nine serum metabolites as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group but not in the disease controls. Cytokine levels were not associated with PET/CT activity. Combining CRP, ESR, and TBR_MDS with choline levels, a composite index was generated to distinguish active and inactive LV-GCA (20.4 vs. 11.62, p = 0.001). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for everyday clinical practice.

Giant Cell Arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial-GCA and Large Vessel Vasculitis (LV)-GCA, involving the thoracic aor-ta and its branches. 18F-fluorodeoxyglucose positron emission tomography-computed tomogra-phy (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosis of patients with systemic disease. However, its association with soluble inflammatory markers is still elu-sive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT pos-itive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The Most-Disease-Segment Target-to-Background Ratio (TBRMDS) was calculated for 9 LV-GCA patients, while 12 cranial-GCA and 7 Polymyalgia Rheumatica patients with negative initial PET/CT served as disease controls. Serum macrophage-related cytokines were evaluated by Cytometric Bead Array (CBA). Finally, previously published NMR-metabolomics data acquired at the same blood sampling were associated with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.45 vs. 2.55, p=0.008). The analysis identified 6 serum metabolites, as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group, but not the disease controls. Cytokine levels were not associated with PET/CT activity. Combining with CRP, ESR, and TBRMDS a composite index was generated to depict well the differences between active and inactive systemic LV-GCA (25.45 vs 11.45, p=0.0039). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for the everyday clinical practice.

Helicobacter pylori (H. pylori) infection induces DNA Double-Strand Breaks (DSBs) and consequently activates the DNA Damage Response pathway (DDR) and senescence in gastric epithelium. We studied DDR activation and senescence before and after the eradication of the pathogen. Gastric antral and corpus biopsies of 61 patients with H. pylori infection, prior to and after eradication treatment, were analyzed by means of immunohistochemistry/immunofluorescence for DDR marker (γH2AΧ, phosporylated ataxia telangiectasia-mutated (pATM), p53-binding protein (53BP1) and p53) expression. Samples were also evaluated for Ki67 (proliferation index), cleaved caspase-3 (apoptotic index) and GL13 staining (cellular senescence). Ten H. pylori (−) dyspeptic patients served as controls. All patients were re-endoscoped in 72-1361 days (mean value 434 days), and tissue samples were processed in the same manner. The eradication of the microorganism, in human gastric mucosa, downregulates γH2AΧ expression in both the antrum and corpus (p = 0.00019 and p = 0.00081 respectively). The expression of pATM, p53 and 53BP1 is also reduced after eradication. Proliferation and apoptotic indices were reduced, albeit not significantly, after pathogen clearance. Moreover, cellular senescence is increased in H. pylori-infected mucosa and remains unaffected after eradication. Interestingly, senescence was statistically increased in areas of intestinal metaplasia (IM) compared with adjacent non-metaplastic mucosa (p < 0.001). In conclusion, H. pylori infection triggers DSBs, DDR and senescence in the gastric epithelium. Pathogen eradication reverses the DDR activation but not senescence. Increased senescent cells may favor IM persistence, thus potentially contributing to gastric carcinogenesis.