Cutaneous lymphocyte antigen (CLA) T cells increased and plasmacytoid dendritic cells (pDC) decreased in CRB1-associated retinal dystrophy

Abstract

Purpose : Patients with a CRB1-associated retinal dystrophy (RD) show substantial phenotypic variability even within families. Some patients have symptoms of ocular inflammation resembling uveitis, indicating a possible role for the immune system in disease progression. Previous studies show a dysregulation of leukocyte composition in peripheral blood in uveitis patients, which has not yet been investigated extensively in retinal dystrophy patients. We determined the composition of peripheral blood mononuclear cells (PBMCs) of patients with CRB1-RD in order to ascertain activation of immune system components.

Methods : Case-control study. 33 patients with a confirmed CRB1-gene mutation and 32 healthy controls were included in this study. Mean age and sex of the patient and healthy control groups were 26.0 ± 15.6 years with 58% female (n = 19), and 25.1 ± 8.8 years with 53% female (n = 17), respectively. PBMCs were isolated from venous blood samples of patients and healthy controls. None of the patients had acquired immune disease or received anti-inflammatory treatment at the time of blood sample taking. 43-parameter flow cytometry was used for immunophenotyping. Data were analysed by FlowSOM automatic gating and manual gating.

Results : FlowSOM automatic gating identified multiple significantly different PBMC abundances in patients compared to healthy controls. The abundance of CD8^-CD4⁺CLA⁺ T cells (p < 0.001) and CD8⁺CLA⁺ T cells (p < 0.001) are significantly increased, whereas CD303⁺CD123⁺ plasmacytoid dendritic cells (p = 0.02) and IgA⁺CD24⁺CD38⁺IgM^- B cells (p = 0.014) are both significantly decreased in patients. Manual gating confirmed these findings.

Conclusions : Immunophenotyping of PBMCs of 33 patients with CRB1-associated retinal dystrophy show a significant increase of CD8^-CD4⁺CLA⁺ T cells and CD8⁺CLA⁺ T cells, and a significant decrease of plasmacytoid dendritic cells (pDCs) and IgA⁺CD24⁺ B cells. A decreased pDC abundance is also observed in uveitis and other inflammatory conditions. The cause of decrease of these cells is unknown. Although the pathogenesis of CRB1-RD and uveitis is different, both entities show a similar dysregulation in peripheral blood leukocyte composition.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

FlowSOM automatic clustering shows a significantly higher abundance of CLA⁺ T cells in patients compared to controls. These cells were verified with manual gating.