Abstract
Previous studies have established that disturbed lymphocytes are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) syndrome. Accordingly, glucocorticoids (GCs), with their well-recognized immune-suppressive function, have been widely used for treatment of VKH patients with acute relapses. However, the systemic response of diverse immune cells to GC therapy in VKH is poorly characterized. To address this issue, we analyzed immune cell subpopulations and their phenotype, as well as cytokine profiles in peripheral blood from VKH patients (n=25) and health controls (HCs, n=21) by flow cytometry and luminex technique, respectively. For 16 patients underwent GC therapy (methylprednisolone, MP), the aforementioned measurements as well as the transcriptome data from patients before and after one-week’s GC therapy were also compared to interrogate the systemic immune response to GC therapy. Lymphocyte composition in the blood was different in VKH patients and HCs. VKH patients had significantly higher numbers of T cells with more activated, polarized and differentiated phenotype, more unswitched memory B cells and monocytes, as compared to HCs. MP treatment resulted in decreased frequencies of T cells and NK cells, inhibited NK cell activation and T cell differentiation, and more profoundly, a marked shift in the distribution of monocyte subsets. Collectively, our findings suggest that advanced activation and differentiation, as well as dysregulated numbers of peripheral lymphocytes are the major immunological features of VKH, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets, which might combinatorically result in the inhibition of the pathogenic immune response.
Highlights
Vogt-Koyanagi-Harada syndrome (VKH syndrome) is an acute diffuse uveitis characterized by bilateral, diffuse granulomatous resulted from stromal choroiditis, accompanied by neurologic manifestations consisting of headache and nausea [1]
There were no significant changes in granulocytes, total lymphocytes and CD3+CD56+ T cells in terms of both absolute number and relative frequency (Figures S1A, B), the numbers of T cells and B cells displayed an increased tendency, this difference failed to reach statistical significance (Figures 1C, D)
Our results in VKH elaborate the proposed notion that T cells and B cells might be pathogenic and NK cells could be protective in most autoimmune diseases, and raise a question regarding the functional role of increased monocytes
Summary
Vogt-Koyanagi-Harada syndrome (VKH syndrome) is an acute diffuse uveitis characterized by bilateral, diffuse granulomatous resulted from stromal choroiditis, accompanied by neurologic manifestations consisting of headache and nausea [1]. Ocular manifestations of this disease include retinal detachment or subretinal fluid, papilledema and hyperemia of the optic disk at initial onset. The pathogenesis of VKH has been extensively studied during the past decades. The role of these cells in the pathogenesis of VKH is not systemically addressed
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