Interleukin 21, Interleukin 23, and Transforming Growth Factor β1 in HLA-A29-Associated Birdshot Retinochoroidopathy

Abstract

To determine the peripheral levels of 20 immune mediators in serum samples from patients with birdshot retinochoroidopathy (BSRC). Single-center prospective case-control study. The serum of 17 BSRC patients during different phases of disease activity and therapy were analyzed with a quantitative multiplex sandwich enzyme-linked immunosorbent assay-based microarray to determine the levels of 20 immune mediators (T cell and proinflammatory). The serum of 12 healthy volunteers was used as controls. Serum levels of interleukin (IL)-21 (P = .0005), IL-23 (P = .0005), and transforming growth factor (TGF)-β1 (P = .0011) were elevated in BSRC patients with active disease naïve to systemic therapy compared with that of controls. There was no significant difference in the serum levels of immune mediators between controls and BSRC patients who had a current or past history of IMT or who were in remission. The levels of IL-21, IL-23, and TGF-β1 were positively correlated (IL-23/IL-21, r = 0.91; TGF-β1/IL-21, r = 0.97; TGF-β1/IL-23, r = 0.87; for all, P < .0001). BSRC patients with active disease naïve to systemic therapy have elevated serum levels of 3 key immune mediators known to promote T helper 17 (Th17) cells in autoimmune disease. Our results suggest that IL-21, IL-23, and TGF-β1 may play an important role in the development of site-specific Th17 cell-mediated inflammation in BSRC, which underscore the importance of systemic therapy and offer new insights into the potential of targeted treatments.