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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.

SUBMITTER: Jiang H

PROVIDER: S-EPMC8113950 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose:This study was designed to systemically characterize and compare the immunological profiles of peripheral blood from patients with VKH and healthy controls. The influence of MP, which has been the most widely prescribed GC in VKH therapy, on immune phenotypes in peripheral blood from VKH patients was also evaluated. Our investigation will offer a better understanding of the function, activation and differentiation status of the leukocyte subpopulations during autoimmune VKH and after GC therapy, and may facilitate a more specific therapeutic regimen for this particular disease, which is a major cause of visual impairment. Methods:Total RNAs of whole blood cells were extracted in accordance with the manual of PAXgene tube (BD bioscience, San Jose, CA, USA). Preparation of library and transcriptomic sequencing were carried out using Illumina novaseq 6000 (Novogene Bioinformatics Technology Co., Ltd., Beijing, China). Differential expression analysis of two conditions/groups (two biological replicates per condition) was performed using the DESeq2 R package (1.16.1). DESeq2 provide statistical routines for determining differential expression in digital gene expression data using a model based on the negative binomial distribution. The resulting P values were adjusted using the Benjamini and Hochberg’s approach for controlling the false discovery rate. Genes with an adjusted P value <0.05 found by DESeq2 were assigned as differentially expressed. Results:The 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 of monocytes toward an anti-inflammatory phenotype. Collectively, our findings suggest that the occurrence of VKH mainly affects the activation status and numbers of peripheral lymphocytes, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets and polarizes monocyte toward a suppressive phenotype, endowing them with the capacity to inhibit the pathogenic immune response. Conclusion:The comprehensive analysis of blood leukocytes from VKH patients and HCs described in this study reveals a perturbation of the lymphocyte compartment in VKH, exemplified by the increased activation and proliferation of T cells in VKH patients. GC therapy not only affects the proliferation and apoptosis of lymphocytes, especially T cells, but also affects the distribution of monocyte subsets. Our results also indicate that CD56+ monocytes may be regulatory and contribute to the remission of inflammatory autoimmune diseases such as VKH, suggesting that this monocyte subset could represent a potentially useful cellular therapeutic target in certain inflammatory diseases, especially when patients have strong side effects in response to GC therapy.

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

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