Synovial Inflammation as an Essential Feature of Osteoarthritis: Unravelling the Role of Viral Agents and Associations with Cognitive and Mental Health Outcomes. Doctoral Thesis
Bibliographic record
Abstract
Osteoarthritis (OA) remains the most prevalent joint disorder worldwide, particularly affecting individuals over the age of 50. Although numerous pathogenetic mechanisms contribute to the initiation and progression of articular cartilage degeneration, synovial inflammation plays a significant role in the disease process. While the degree of inflammation in OA is less pronounced and not systemic as seen in inflammatory arthritides, its involvement constitutes a critical element in the pathogenesis, progression, and persistence of the disease. The effects of synovial inflammation extend beyond the stimulation of catabolic processes, encompassing the acceleration of cellular senescence and potential contributions to neuropsychiatric disturbances, including mood and cognitive alterations. While inflammation in OA has been previously investigated, the complex and multifactorial nature of its triggers, such as latent viral infections, requires further study. Moreover, the potential associations between synovial inflammation and depressive symptoms or cognitive decline remain insufficiently understood and warrant comprehensive investigation. In this study, two independent cohorts of 54 and 50 individuals undergoing joint replacement surgery were analysed. In the first cohort, a focused investigation on the persistence of parvovirus B19 (B19V) and human herpesvirus 7 (HHV-7) in the synovial membrane and their potential impact on inflammation was conducted using the Krenn synovitis histological scoring system. Immunohistochemical analyses were performed to evaluate the expression of tumour necrosis factor alpha (TNF-α) and transforming growth factor-beta (TGF-β) in synovial tissue and to investigate their association with viral presence. Nonetheless, HHV-7-positive samples showed a significant correlation between CD4+ lymphocyte infiltration and TNF-α expression, suggesting immune cell-specific responses to latent viral presence. Additionally, the role of S100 protein expression in the inflammatory process was assessed, showing a positive correlation. This integrative approach aimed to elucidate the contribution of chronic viral persistence and local immune responses to the synovial pathology observed in OA. The second cohort was evaluated for synovial inflammation and its correlation with urinary biomarkers, using ELISA method: C-telopeptide of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP), TNF-α, TGF-β1 and neuropsychological assessments, including Montreal Cognitive Assessment (MoCA), Patient Health Questionnaire-9 (PHQ-9), and Generalised Anxiety Disorder-7 (GAD-7) tests. In the second cohort, histologically confirmed synovitis scores varied widely and correlated with urinary TGF-β1 levels. Cognitive (MoCA) and affective (PHQ-9, GAD-7) scores showed significant associations with synovial inflammation, particularly in patients with moderate-to-high inflammatory grades. Cluster analysis revealed distinct inflammatory phenotypes with gender-linked variations in symptom severity and cognitive and affective symptom outcomes. The Doctoral Thesis was developed at RSU AAI Joint Laboratory of Electron Microscopy and the RSU Department of Internal Diseases, Latvia. Defence of the Doctoral Thesis will take place at the public session of the Promotion Council of Clinical Medicine on 18 December 2025 at 14.00 in the Hippocrates Lecture Theatre, 16 Dzirciema Street, Rīgas Stradiņš University and remotely via online platform Zoom. This Doctoral Thesis was developed with the support of the Fundamental and Applied Research grant No lzp-2018/1-0149 “Interdisciplinary study on the effects of inflammatory joint diseases on neurocognitive function” and support of European grant “Reducing networking gaps between Rīga Stradiņš University (RSU) and internationally-leading counterparts in viral infection-induced autoimmunity research” (VirA)”. 3.2. Clinical Medicine; Sub-Sector – Internal Medicine. Keywords: Synovial inflammation; HHV-7; Parvo-B19; cognitive decline; depression; anxiety.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".