June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
HSP-Specific T Cell Counts in Boston Keratoprosthesis Type I Patients
Author Affiliations & Notes
  • Chhavi Saini
    Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Kin-Sang Cho
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Julia Devlin
    Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Li Pan
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
    School of Optometry, The Hong Kong Polytechnic University, Hong Kong, Hong Kong
  • Shuhong Jiang
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Eleftherios I Paschalis
    Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • James Chodosh
    Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Dongfeng Chen
    Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Lucy Q. Shen
    Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Chhavi Saini Massachusetts Eye and Ear, a non-profit hospital and manufacturer of Boston keratoprosthesis device. , Code E (Employment); Kin-Sang Cho Massachusetts Eye and Ear, a non-profit hospital and manufacturer of Boston keratoprosthesis device., Code E (Employment); Julia Devlin Massachusetts Eye and Ear, a non-profit hospital and manufacturer of Boston keratoprosthesis device., Code E (Employment); Li Pan Massachusetts Eye and Ear, a non-profit hospital and manufacturer of Boston keratoprosthesis device. , Code E (Employment); Shuhong Jiang Massachusetts Eye and Ear, a non-profit hospital and manufacturer of Boston keratoprosthesis device., Code E (Employment); Eleftherios Paschalis Massachusetts Eye and Ear, a non-profit hospital and manufacturer of Boston keratoprosthesis device., Code E (Employment); James Chodosh Massachusetts Eye and Ear, a non-profit hospital and manufacturer of Boston keratoprosthesis device., Code E (Employment); Dongfeng Chen Massachusetts Eye and Ear, a non-profit hospital and manufacturer of Boston keratoprosthesis device., Code E (Employment); Lucy Shen Massachusetts Eye and Ear, a non-profit hospital and manufacturer of Boston keratoprosthesis device., Code E (Employment)
  • Footnotes
    Support  Boston Keratoprosthesis Fund, NEI Grant EY031696 and Harvard NeuroDiscovery Center Grant.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 943 – A0412. doi:
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      Chhavi Saini, Kin-Sang Cho, Julia Devlin, Li Pan, Shuhong Jiang, Eleftherios I Paschalis, James Chodosh, Dongfeng Chen, Lucy Q. Shen; HSP-Specific T Cell Counts in Boston Keratoprosthesis Type I Patients. Invest. Ophthalmol. Vis. Sci. 2022;63(7):943 – A0412.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

 

 

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