Immunological Profiling of Leukocyte Subset Proportions and Novel Blood Biomarkers in the Acute Phase of Ocular Sarcoidosis and Vogt–Koyanagi–Harada Disease: An Exploratory Pilot Study

Aberrant pathogenic immune responses drive autoimmune uveitides; however, comprehensive leukocyte profiling in the conditions remains limited. Here, this exploratory pilot study aimed to elucidate the immunodynamics of ocular sarcoidosis (OS) and Vogt–Koyanagi–Harada disease (VKH) to identify blood diagnostic biomarkers during their acute phases. We performed a prospective observational analysis of ten newly diagnosed, treatment-naïve OS patients and seven VKH patients during their acute phases, along with eight healthy controls (HCs). Mass cytometry was utilized to quantify the proportions of 37 distinct leukocyte subsets. In OS group, the proportion of CD8+ naive was lower than in both VKH and control groups. Furthermore, the proportions of CD8+ central memory and γδ T cells were decreased compared to HC group. Hierarchical cluster analysis categorized the leukocyte subsets into four principal clusters: Cluster A (Th17-like, monocytes, neutrophils, etc.), Cluster B (Tregs, B cells, NK cells, basophils, etc.), Cluster C (CD8+ T cells, Th1-like, Th2-like, DCs, etc.), and Cluster D (CD4+ terminal effector, CD8+ terminal effector, and CD66b− neutrophils). Compared to HC group, the abundance of Cluster A was relatively high in OS group, and the abundance of cluster B was relatively high in VKH group. In OS group, the proportions of CD8+ T cells and CD8+ terminal effector correlated negatively with serum ACE and sIL-2R levels. ROC curve analysis estimated that CD4+/CD8+ ratio (cut-off value: ≥3.46), the proportion of monocytes (≥9.41%), and the decreased proportions of CD3+ T cells (≤43.9%) and CD8+ T cells (≤10.0%) in peripheral blood may serve as potential blood biomarkers for diagnosing OS. The exploratory pilot study provides a comprehensive and simultaneous data of leukocyte subset proportions in the acute phase of OS and VKH, and our preliminary findings suggest that the proportions of specific leukocyte subsets may represent potential candidates for blood-based biomarkers in the diagnosis of OS.