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TitleTranscriptomic profiling of iris tissue highlights B cell-mediated immunity in Vogt-Koyanagi-Harada disease
PurposeTo explore the molecular pathological changes and immunopathogenesis of intraocular inflammatory sites in Vogt-Koyanagi-Harada (VKH) disease.
MethodsThe mRNA-seq, bioinformatics analysis, RT-qPCR, and flow cytometry were performed.
ResultsCompared with healthy controls, a total of 3522 differentially expressed genes (DEGs) were identified in the iris of the VKH group. Cell type enrichment analysis by xCell showed that the overall immune infiltration level in the iris of the VKH group was significantly increased, of which B cells and their subsets with the highest enrichment scores exhibited the greatest difference as compared with healthy controls. Specifically, B cells, memory B cells, class-switched memory B cells, and plasma cells were significantly enriched in the iris of the VKH group. Furthermore, GO and KEGG enrichment analysis showed that B cell-related biological processes such as B cell activation and B cell receptor signaling pathway were also prominently enriched. GSEA further revealed that B cell-related biological processes were distinctively associated with VKH disease. The mRNA expression of B cell marker genes (including CD20, CD19, CD79A, CD79B, MZB1, CD22, CD27, and SDC1) was also notably upregulated in the iris of VKH patients. Similarly, we found that the proportions of memory B cells, class-switched memory B cells, and plasmablasts were significantly increased in the peripheral blood of patients with active VKH.
ConclusionThese findings highlight a previously underappreciated role of B cell subsets in the development of intraocular inflammation in patients with VKH, and thus targeting B cells may be a new therapeutic strategy for this disease.
Conflict of interestNo
Authors 1
Last nameDENG
Initials of first name(s)Y
Departmentophthalmology
CityChongqing
CountryChina
Authors 2
Last nameYang
Initials of first name(s)P
Departmentophthalmology
CityChongqing
CountryChina