Classification of Peripheral Blood Leukocyte Phenotypes and Serum Cytokines in Vogt-Koyanagi-Harada Disease before and after Glucocorticoid Therapy

Tomohito Sato; Nanae Taniguchi; Yoshiaki Nishio; Masataka Ito; Masaru Takeuchi

doi:10.3390/jcm12247742

Classification of Peripheral Blood Leukocyte Phenotypes and Serum Cytokines in Vogt-Koyanagi-Harada Disease before and after Glucocorticoid Therapy

J Clin Med. 2023 Dec 17;12(24):7742. doi: 10.3390/jcm12247742.

Authors

Tomohito Sato¹, Nanae Taniguchi¹, Yoshiaki Nishio¹, Masataka Ito², Masaru Takeuchi¹

Affiliations

¹ Department of Ophthalmology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
² Department of Developmental Anatomy and Regenerative Biology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.

Abstract

Vogt-Koyanagi-Harada disease (VKH) is an autoimmune disease, and glucocorticoid therapy (GC) is widely used for VKH. We provided a profile of leukocyte populations and serum cytokines in VKH patients under GC. A prospective observational study was conducted on three treatment-naïve VKH patients. Peripheral blood samples were collected from the patients before GC (VKH-acute) and after 6 months (VKH-remission), and healthy individuals were used as controls. Proportions of 37-type leukocytes and levels of 27-kind cytokines were measured by mass cytometry and multiplex bead analysis. Property similarity was analyzed using hierarchical cluster analysis. The leukocytes and cytokines were broadly classified into four and three clusters: (1) a cluster with high intensity in VKH-acute consisting of B cells, Th2-like, Th17-like, basophils, and IL-7 and IP-10; (2) a cluster with high intensity in VKH-remission composed of monocytes, neutrophils, IL-4, and TNFα; in leukocytes, (3) a cluster with low intensity in VKH-acute and -remission consisting of CD8⁺ T cells, Th1-like, and NKT cells; (4) a cluster with low intensity in VKH-remission composed of NK cells, Tregs, and DCs; and in cytokines, (5) a cluster with high intensities in VKH-acute and -remission comprising G-CSF, MCP-1, eotaxin, and IL-17A. These findings suggest that inflammatory composition in blood during the acute phase of VKH represents complex hyperimmune responses dominantly driven by Th and B cells.

Keywords: Vogt–Koyanagi–Harada disease; cytokine; glucocorticoid; leukocytes; mass cytometry; multiplex bead analysis.

Grants and funding

This research was funded by a Research Grant from The Uehara Memorial Foundation; Daiwa Securities Health Foundation; a Grant-in-Aid for Scientific Research C from the Japan Society for the Promotion of Science (20K09840, 23K09036); and a Grant-in-Aid for Advanced Medical Development from National Defense Medical College. The APC was funded by the Research Grant from The Uehara Memorial Foundation. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.