Unravelling T‐cell dynamics and immune responses in initial and recurrent uveitis

This study aimed to identify novel serological targets and investigate immune responses in patients with non‐infectious uveitis, focusing on differences between initial onset and recurrent episodes. Differential gene expression analysis, immunocyte typing and T‐cell receptor (TCR) gene analysis were conducted on RNA‐sequenced peripheral blood samples from healthy individuals (n = 6) and non‐infectious uveitis patients (n = 12), divided into 6 patients each at initial onset and recurrent stages. Peripheral blood T‐cell types were analysed using flow cytometry. Bioinformatics methods included tools for RNA sequencing data processing, CIBERSORT for immune cell type prediction and specialized software for TCR repertoire analysis. Findings indicated that individuals with recurrent uveitis demonstrated a stronger adaptive immune response and a more pronounced immune imbalance compared to those with initial onset. Memory T cells were predominant in recurrent episodes, suggesting their potential role as biomarkers for disease progression. Significant differences in TCR diversity and V(D)J gene usage were observed between the various uveitis groups and healthy controls. Importantly, 38 uveitis‐specific TCR sequences showed substantial expansion in the uveitis patients compared to controls. An elevated expansion of these specific TCR sequences was associated with an increased risk of uveitis development. The study highlights the critical role of adaptive immune responses and specific immune cell types in the pathogenesis of recurrent uveitis. Identification of the uveitis‐specific TCR repertoire set could provide deeper insights into the disease and facilitate the development of targeted therapies for uveitis patients. Active T‐cell‐mediated adaptive immunity can be detected in patients with uveitis, especially in recurrent patients. 38 highly expansion uveitis‐specific TCR sequences were identified, which is associated with a more intense and extensive epitope exposure during recurrent. Our study provides novel immunotherapeutic targets and serological indicators for disease monitoring for treatment of uveitis.