Novel diagnostic method for B cell vitreoretinal lymphoma by identification of regulatory T cells and PD-1⁺ cytotoxic T lymphocytes in the vitreous via flow cytometry

Aims: To investigate the significance of regulatory T cells (Tregs) and programmed cell death 1 (PD-1)⁺ cytotoxic T lymphocytes (CTLs) in the vitreous of patients with vitreoretinal lymphoma (VRL) and uveitis.

Methods: This study involved 51 patients with VRL and uveitis, 15 males and 36 females (mean age: 72 years, range: 51-86 years), who underwent vitrectomy at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan, from December 2019 to February 2024. All patients underwent lymphocyte surface antigen analysis via flow cytometry, and the proportion of Tregs in CD4⁺ T lymphocytes and PD-1⁺ CTLs in CD8⁺ T lymphocytes was measured.

Results: This study involved B cell VRL (B-VRL, n=16), sarcoidosis (n=8), human herpesvirus (HHV)-associated uveitis (n=7), human T cell lymphotropic virus type 1 associated uveitis (HAU, n=3) and unclassifiable uveitis (n=17) cases. The median proportions of Tregs were significantly lower in B-VRL (2.2%) compared with sarcoidosis (8.5%), HHV-associated uveitis (16.4%) and unclassifiable uveitis (10.1%) (p<0.05). Conversely, a significantly higher proportion of PD-1⁺ CTLs was found in B-VRL (95.6%) compared with sarcoidosis (61.1%), HHV-associated uveitis (67.1%) and unclassifiable (64.8%) (p<0.05). Receiver operating characteristic analysis of Tregs and PD-1⁺ CTLs proportions in B-VRL revealed high area under the curve values of 0.913 and 0.940, respectively.

Conclusions: Our findings indicate that analysis of the ratio of Tregs and PD-1⁺ CTLs via flow cytometry is helpful in diagnosing B-VRL.