• Written By: Ralph Levinson
    Uveitis

    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. To the authors' knowledge, this is the first systematic study of the intraocular fluid and the 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, strong associations with HLA-A29, and with KIR (killer immunoglobulin receptor) genes. Indeed BCR is 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 birdshot chorioretinopathy plus controls (normal patients undergoing cataract surgery).

    Compared to controls, patients with BSCR had higher aqueous concentrations of T-cell mediators interleukin (IL)-2 and IL-17 (which is produced by T cells [Th-17 cells] and some KIR bearing cells, including some T cells and NK cells) and proinflammatory mediators IL-1β, 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 indicated that the elevated cytokines 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 BCR, indicating production by cells in the eye. That they found positive results at all is a bit surprising as in most patients with BCR there are few cells in the anterior chamber in this posterior uveitis.

    The authors point out that anti-IL17 antibodies have been evaluated on 11 patients with uveitis (not BSCR) in a phase II study with promising results. While they advise caution, these results are promising and offer a biologic rationale for considering anti-IL17 therapy if such treatment continues to hold promise in treating uveitis.

    It would also be of interest to know whether the change in IL17 levels is a function of chronic T-cell mediated inflammation or is specific to BSCR.