Abstract
Purpose:
Non-paraneoplastic autoimmune retinopathy (AIR) is a poorly understood immunological eye disease that can lead to vision loss. AIR is usually identified by a combination of clinical symptoms (abnormal ERG, visual field abnormalities, etc) as well as the presence of peripheral antiretinal antibodies. However, little is known about the cause or mechanism of the disease. Since immunosuppressives have been shown to effectively treat some patients with AIR, it is advantageous to explore the markers present on peripheral immune cells. The purpose of this study is to evaluate biomarker expression on peripheral immune cells from AIR patients, compared to that from other subtypes of uveitis patients and healthy donors.
Methods:
Whole blood samples were taken from individuals presenting with non-paraneoplastic AIR, other uveitis diseases, and age-matched healthy donors. Whole blood staining for immune cell phenotyping was performed using a standard 4-color flow cytometry protocol.
Results:
AIR patients have statistically significant lower levels of CTLA4 positive CD4 positive T-cells when compared to other subtypes of uveitis patients. Lower levels of CD163 positive monocytes were also detected in AIR patients compared to uveitis patients. T cells from patients who had received Rituximab treatment showed markedly decreased levels of CD40L, a costimulatory molecule expressed on T cells that regulates B cell function by engaging CD40 on B cells, compared to those receiving no treatment or other immunosuppressive therapies.
Conclusions:
CTLA4 receptors are involved in downregulating the immune system, thus decreased CTLA4 expression in AIR patients suggests that hyperactivity of the immune T cell response could be a contributing factor to the retinopathy. CD163 is a scavenger receptor known to be upregulated in many inflammatory disorders, including tested control uveitis patients in this study. It was not upregulated in AIR patients, indicating that the mechanism of action of AIR may be different from typical uveitis. The significant decrease in CD40L positive cells following Rituximab treatment is consistent with previous publications in which the same observation was also reported for patients with SLE treated with Rituximab. Exploring the biomarkers present in the peripheral immune cells of AIR patients may help us understand the pathogenic mechanism and facilitate clinical management of disease.
Keywords: 432 autoimmune disease •
467 clinical laboratory testing