Immune Phenotyping of Patients With Acute Vogt-Koyanagi-Harada Syndrome Before and After Glucocorticoids Therapy

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.

Association Between Interleukin 35 Gene Single Nucleotide Polymorphisms and the Uveitis Immune Status in a Chinese Han Population

“…We have analyzed the relationship between IL-35 gene SNPs and genetic susceptibility in the Chinese Han population with uveitis (mainly BD and VKH syndrome). Our results suggest that the IL-12 p35 rs2243131 A/C allele was related to the disorder of Breg cells in VKH patients, and IL-35 and its subunit IL-12p35 preferentially induced the expansion of Breg and Treg cells, inhibited the activation of DC, and inhibited the expansion of pathogenic Th17 and Th1 cells ( 13 , 14 , 32 ), to slow down the development of autoimmune diseases. Thus, the IL-12 p35 A/C allele mutation may be the key factor of Breg cells reduction in VKH patients.…”

Case report: Bilateral panuveitis resembling Vogt-Koyanagi-Harada disease after second dose of BNT162b2 mRNA COVID-19 vaccine

“…VKH disease is an acute panuveitis characterized by bilateral, diffuse granulomatous lesions resulted from stromal choroiditis, accompanied by neurologic manifestations of headache and nausea ( 23 ). Characteristic ocular manifestations of VKH disease at the time of onset include sudden blurred vision, bilateral panuveitis, diffuse granulomatous choroiditis with exudative retinal detachment, vitritis and optic disc swelling ( 18 , 24 ). The prevalence of VKH disease varies among different countries and ethnic groups ( 18 ).…”

“…Characteristic ocular manifestations of VKH disease at the time of onset include sudden blurred vision, bilateral panuveitis, diffuse granulomatous choroiditis with exudative retinal detachment, vitritis and optic disc swelling ( 18 , 24 ). The prevalence of VKH disease varies among different countries and ethnic groups ( 18 ). In Asian, VKH disease represents one of the most common uveitis entities ( 25 ).…”

“…In Asian, VKH disease represents one of the most common uveitis entities ( 25 ). VKH disease is a complex disease involving multiple interactions among different immune cell populations ( 18 ). VKH patients are sensitized to melanocyte epitopes, and patients with HLA-DR4/HLA-DRB1*0405 recognize a broader melanocyte derived peptide repertoire ( 26 ).…”

“…Glucocorticosteroid (GC) therapy was initiated according to the standard treatment for VKH disease ( 18 ). In the clinical course of treatment ( Supplementary Figure 1 ), we paid attention to deterioration of visual acuity and subfoveal choroidal thickness, and tapered the dose of prednisolone in accordance with the assessment of uveitis activity proposed by The standardization of Uveitis Nomenclature (SUN) Working Group ( 14 ).…”