Ana Mendizabal-Sasieta

Background. Graves' disease (GD) is an autoimmune thyroid condition driven by thyroid-stimulating hormone receptor (TSHR) autoantibodies (TSI), frequently leading to hyperthyroidism and vision-threatening Graves' orbitopathy (GO) or Thyroid Eye Disease (TED). Despite its prevalence, the biological mechanisms driving disease onset, T-cell-mediated pathogenesis, and treatment resistance remain unclear. Because individual T-cell receptor (TCR) repertoires are highly private, cross-sectional snapshots often obscure these mechanistic and pathogenic signals. Longitudinal immune tracking overcomes this by using intra-individual baselines to track disease initiation, evolution, and therapeutic response. Methods and Results. In a longitudinal tracking study, we followed a patient who developed dry eyes ~7 months postpartum, initially misdiagnosed as routine conjunctivitis. She was subsequently diagnosed with TSI-positive GD. Approximately 10 months later, she developed active, steroid-refractory GO/TED. Normalization of thyroid hormones with thiamazole failed to halt orbital disease progression. Subsequent high-dose pulse corticosteroid therapy failed to control ocular inflammation and induced elevated intraocular pressure. Switching to an anti-IL-6 receptor antagonist (tocilizumab) achieved rapid and complete clinical remission of orbital inflammation. Uniquely, peripheral blood mononuclear cells (PBMCs) had been banked across a 5-year window (2021-2026), enabling continuous longitudinal immune monitoring (osLifetime), spanning pre-onset to post-remission checkpoints. Conclusion. osLifetime provided a real-time view of autoimmune T-cell activity. By monitoring the adaptive immune system across the entire clinical journey, it established a true pre-symptomatic baseline to benchmark disease progression and therapeutic transitions, capturing T-cell remodeling (manifesting as an acute drop in Immune Age alongside rising Inflammaging score), and even distinguishing corticosteroid failure from tocilizumab response. osLifetime turns complex immune dynamics into actionable quantitative signals, especially where routine biochemistry fails to reflect ongoing disease trajectory, paving the way for precision immunomonitoring in GO/TED and beyond.

Injury risk prediction in elite football relies almost exclusively on external load metrics derived from GPS tracking, overlooking the molecular state of the athlete. We monitored 26 male players from FC Barcelona’s first team across the 2025 calendar year, integrating GPS-derived training load with longitudinal blood-based immune monitoring (systemic inflammation and TCR-derived immune age). Immune age acceleration and inflammation were elevated in the 14 days preceding musculoskeletal injuries. A logistic regression model combining external load, inflammation, immune age acceleration, and career injury history reached an overall AUC of 0.678 and a mean per-player AUC of 0.754 (SD 0.146), improving on a GPS-only baseline of 0.541. Applied to 2026 data, the frozen model ranked players who later sustained non-contact musculoskeletal injuries high in the risk distribution. Together, our data suggest multimodal immune monitoring in elite football to reveal the athlete’s internal physiological state, which carries injury-relevant information that external load alone does not capture.