Abstract
Purpose: :
To correlate the serum levels of 20 cytokines from the T helper (Th)1, Th2, and Th17 pathways with disease activity in birdshot retinochoroidopathy (BSRC).
Methods: :
Single center cohort study of 4 BSRC patients, and 4 normal controls. Immunomodulatory therapy (IMT) and disease status were recorded for each patient. Disease activity was assessed with visual acuity, visual field, fundus exam, optical coherence tomography, fluorescein angiography, and electroretinography. Sera were collected, and a quantitative multiplex sandwich ELISA-based microarray assay was used to quantify 20 cytokines: interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17, IL-17F, IL-21, IL-22, IL-23, IL-28, interferon (IFN)-gamma, macrophage inflammatory protein (MIP)-3alpha, transforming growth factor (TGF)-beta1, tumor necrosis factor (TNF)-alpha, TNF-beta, and granulocyte macrophage colony-stimulating factor (GM-CSF). Cytokine levels from patients were compared with normal controls and correlated with IMT and disease activity.
Results: :
IL-21 (p = 0.01), IL-23 (p = 0.02), TGF-beta1 (p = 0.02), and TNF-beta (p = 0.02) were significantly elevated in the sera of BSRC patients compared to normal controls. IL-17 (p = 0.31) and IFN-gamma (p = 0.85) serum levels were not significantly elevated. The subject that had been in IMT-dependent clinical remission for 2 years, had the lowest levels of IL-21 and IL-23 levels. IL-21 and IL-23 levels had a correlation coefficient of r = 0.93.
Conclusions: :
Th17 cells play an important role in autoimmune disease and uveitis. Although standard ELISA assay has not shown elevations of IL-17 in the sera of BSRC patients, a recent multiplex immunoassay of 23 cytokines in BSRC patients revealed that IL-17 and proinflammatory cytokines were concentrated in the aqueous fluid. We confirm that IL-17 is not elevated in the sera of BSRC patients, however both IL-21 and IL-23 levels were significantly elevated and correlated, suggesting that peripheral cytokines may promote Th17 cells in an organ specific manner. In addition, higher IL-21 and IL-23 levels may correlate with active disease.
Keywords: retinochoroiditis • autoimmune disease • cytokines/chemokines