Abstract
Aim
To explore immunoregulatory and anti-inflammatory pathways specifically targeted by a subcutaneous anti-TNFαdrug—adalimumab—which might be relevant for controlling refractory uveitis.
Design
Non-randomized pilot intervention study on the effects of adalimumab on Treg populations and plasma VEGF levels in refractory uveitis patients. Inflammatory and immunological parameters were measured in 12 patients before therapy, and 1 and 6 months after therapy, and analyzed in the context of ophthalmological outcomes. The results were compared with those obtained in 10 systemic prednisone-treated uveitis patients.
Results
After 1 month of treatment, all patients responded, with 67% of adalimumab group and 80% of the corticosteroid group achieving inactivity (P=0.5). Unlike steroid-treated patients, a significant increase in T-regulatory CD4+ CD25high Foxp3+ CD127− cells was observed in adalimumab patients after 1 month of treatment, and maintained after 6 months (P=0.003). A significant adalimumab-specific drop in plasma VEGF was observed after 1 and 6 months of treatment (P=0.019). In every single patient, Tregs but not VEGF correlated with disease activity.
Conclusions
In refractory uveitis patients treated with adalimumab, clinical efficacy may be mediated through upregulation of Tregs in addition to modulation of VEGF-mediated inflammatory pathways. These biological properties, which were not observed in patients treated with corticosteroids, may reflect the specificity of TNF-αtargeting.
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Acknowledgements
We are grateful to the patients and controls for their participation in this study.
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Dr JG Ruiz de Morales has received speaker honoraria from Abbott Laboratories (less than 10.000€). Dr Ruiz de Morales currently receives funding through a research grant (2010/A/531) from the Department of Health of the Junta de Castilla y León, Spain (SACYL).
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Calleja, S., Cordero-Coma, M., Rodriguez, E. et al. Adalimumab specifically induces CD3+ CD4+ CD25high Foxp3+ CD127− T-regulatory cells and decreases vascular endothelial growth factor plasma levels in refractory immuno-mediated uveitis: a non-randomized pilot intervention study. Eye 26, 468–477 (2012). https://doi.org/10.1038/eye.2011.320
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DOI: https://doi.org/10.1038/eye.2011.320
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