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 non-randomized pilot intervention study.
OBJECTIVE
To explore immunoregulatory and anti-inflammatory pathways specifically targeted by a subcutaneous anti-TNFαdrug-adalimumab-which might be relevant for controlling refractory uveitis.


METHODS
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-αtargeting.
Department of Clinical Immunology, Complejo Hospitalario Universitario de León, León, Spain.
S
S
Calleja
M
M
Cordero-Coma
E
E
Rodriguez
M
M
Llorente
M
M
Franco
J G
JG
Ruiz de Morales
D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068879:Adalimumab