HSP-Specific T Cell Counts in Boston Keratoprosthesis Type I Patients

Abstract

Purpose : Prior animal studies have shown that T cell specific for heat shock proteins (HSPs) play an important role in glaucomatous neurodegeneration. Given the high incidence of glaucoma in patients with Boston keratoprosthesis type I (KPro), we investigated the levels of HSP specific CD4⁺ T-lymphocytes in the peripheral blood of patients with KPro.

Methods : Adult patients with KPro and healthy control subjects were prospectively enrolled. Patients with any autoimmune or immunodeficiency diseases were excluded. Peripheral blood monocytes (PBMC) were isolated from the blood of each participant and stimulated with HSP-27 or another member of the small HSP family, α-crystallin. Both interferon gamma+ helper T cells (Th1) and transforming growth factor beta+ regulatory T cells (Treg) were quantified by flow cytometry and presented as percentage of total PBMC counts. Retinal nerve fiber layer thickness (RNFLT) was measured for all. Ophthalmic data were collected for the KPro eye for KPro patients and worse eye (based on RNFLT) for controls.

Results : KPro patients (n=6) with an average of 9.2±5.0 years from their first KPro surgery and healthy controls (n=13) were similar in age, gender, body mass index and intraocular pressure (IOP) (p>0.22 for all; Table 1), although all KPro patients were treated for IOP. Best corrected visual acuity, cup to disc ratio and average RNFLT were worse for KPro patients (0.4±0.3 LogMAR, 0.7±0.3 and 63.5±33.5 µm, respectively) compared to controls (0.05±0.09 LogMAR, 0.3±0.1 and 95.1±11.7 µm respectively; p≤0.002 for all). Total unstimulated Th1 and Treg cell counts were similar in KPro (2.6±6.5% and 0.8±0.9%) and controls (3.3±1.9% and 1.7±1.7%, p>0.25 for both; Figure 1A). After stimulation with HSPs, Th1 cells specific for HSP-27 and α-crystallin were more abundant in KPro patients than controls (10.1±6.6% vs 2.5±2.2%, p=0.001; 8.9±3.1% vs 2.4±0.8%, p<0.001 respectively; Figure 1B), whereas Treg cells specific for HSP-27 and α-crystallin did not differ between the groups (2.2±1.4% vs 0.9±1.7%, p=0.10; 1.0±0.3% vs 0.6±0.8%, p=0.42, respectively; Figure 1B).

Conclusions : Although our findings are preliminary and larger cohorts of patients are being recruited to validate the results, the data suggest robust systemic HSP-specific Th1 responses were induced in patients with KPro. The elevated level of these T-cells may contribute to the prevalent and severe glaucomatous neurodegeneration in these patients.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.