By Ralph D. Levinson, MD
For decades, a strong association between HLA-A29 and birdshot chorioretinopathy (BSCR) suggested that this disease had a T-cell-mediated autoimmune basis. However, evidence was circumstantial, based on observations of increased immune responsiveness to soluble retinal antigen and interphotoreceptor retinoid-binding protein in BSCR patients. The authors of this article believe this is the first systematic study of the intraocular fluid and serum of BSCR patients. The results support the concept that BSCR is a T-cell-mediated autoimmune disease restricted to the eye.
BSCR is interesting to study from a biologic standpoint because of its characteristic clinical findings and strong associations with HLA-A29 and killer immunoglobulin receptor (KIR) genes. Indeed, BCR has been found to have one of the strongest associations with both HLA and KIR of any human disease.
In this study, researchers from the Netherlands used a multiplex immunoassay to determine the levels of 23 immune mediators (T-cell, proinflammatory and vascular-active mediators) in paired aqueous humor and serum samples from 16 patients with BSCR plus controls (normal patients undergoing cataract surgery).
Compared to controls, BSCR patients had higher aqueous concentrations of T-cell mediators interleukin (IL)-2 and IL-17, proinflammatory mediators IL-1β and IL-6, and tumor necrosis factor α. Concentrations of IL-1β, IL-17 and tumor necrosis factor α were also higher than in the concurrent serum samples.
Although immune mediator concentration differences between subjects and controls were not large, the trends indicate that the elevated cytokine levels in the aqueous humor were likely T-cell related. In addition, the values were much higher for these mediators in aqueous humor than in the serum of subjects with BSCR, indicating production by cells in the eye. That the authors found positive results at all is a bit surprising, since in most patients with BSCR, there are few cells in the anterior chamber.
The authors point out that anti-IL-17 antibodies have been evaluated in 11 patients with uveitis (not BSCR) in a phase II study with promising results. While they advise caution, these results offer a biologic rationale for considering anti-IL-17 therapy.
It would also be of interest to know whether the change in IL-17 levels is a function of chronic T-cell mediated inflammation or is specific to BSCR.