Adalimumab specifically induces CD3(+) CD4(+) CD25(high) Foxp3(+) CD127(-) T-regulatory cells and decreases vascular endothelial growth factor plasma levels in refractory immuno-mediated uveitis: a nonrandomized pilot intervention study

作者：Calleja S; Cordero Coma M; Rodriguez E; Llorente M; Franco M; Ruiz de Morales J G

来源：Eye, 2012, 26(3): 468-477.

DOI：10.1038/eye.2011.320

• uveitis
• anti-TNF alpha
• adalimumab
• immunomodulation
• Tregs
• VEGF

Aim To explore immunoregulatory and anti-inflammatory pathways specifically targeted by a subcutaneous anti-TNF alpha drug-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(+) CD25(high) 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-alpha targeting. Eye (2012) 26, 468-477; doi: 10.1038/eye.2011.320; published online 6 January 2012

• 出版日期2012-3