July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Deep Profiling of Circulating Immune Cells in Uveitis Patients with Spondylitis Indicates an Increase of CCR9+ Gut Homing Cells
Author Affiliations & Notes
  • Jay Siak
    Ocular Inflammation and Immunology, Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore
    Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Matthew Schleisman
    Casey Eye Institute and Dept. of Ophthalmology; Division of Arthritis and Rheumatic Disease, Dept. of Medicine, Oregon Health & Science University, Portland, Oregon, United States
  • Claire Mitchell
    Casey Eye Institute and Dept. of Ophthalmology; Division of Arthritis and Rheumatic Disease, Dept. of Medicine, Oregon Health & Science University, Portland, Oregon, United States
  • Lindsey Watson
    Casey Eye Institute and Dept. of Ophthalmology; Division of Arthritis and Rheumatic Disease, Dept. of Medicine, Oregon Health & Science University, Portland, Oregon, United States
  • James T Rosenbaum
    Casey Eye Institute and Dept. of Ophthalmology; Division of Arthritis and Rheumatic Disease, Dept. of Medicine, Oregon Health & Science University, Portland, Oregon, United States
    Ophthalmology, Legacy Devers Eye Institute, Portland, Oregon, United States
  • MARK ASQUITH
    Casey Eye Institute and Dept. of Ophthalmology; Division of Arthritis and Rheumatic Disease, Dept. of Medicine, Oregon Health & Science University, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Jay Siak, None; Matthew Schleisman, None; Claire Mitchell, None; Lindsey Watson, None; James Rosenbaum, Abbvie (C), Eyevensys (C), Gilead (C), Janssen (C), Novartis (C), Pfizer (F), Roche (C), UCB (C), UpToDate (C); MARK ASQUITH, None
  • Footnotes
    Support  NIH-NEI grants EY026572, EY029266-01, EY010572, and Research to Prevent Blindness funding
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1726. doi:https://doi.org/
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      Jay Siak, Matthew Schleisman, Claire Mitchell, Lindsey Watson, James T Rosenbaum, MARK ASQUITH; Deep Profiling of Circulating Immune Cells in Uveitis Patients with Spondylitis Indicates an Increase of CCR9+ Gut Homing Cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1726. doi: https://doi.org/.

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

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Abstract

Purpose : To identify immune cell phenotypes which predict the association with systemic spondylitis among patients with acute anterior uveitis using mass cytometry (CyTOF) deep profiling.

Methods : Peripheral blood mononuclear cells (PBMC) were isolated from 4 subjects with acute anterior uveitis (AAU) and diagnosed axial spondyloarthritis (AxSpA), 7 subjects with AAU without AxSpA and 5 healthy controls. Polyclonally-stimulated PBMC were stained with a panel of 44 metal-conjugated antibodies designed to profile circulating immune cells using mass cytometry. Subsequently CD3+CD56- cells were identified by manual gating and subjected to unbiased cluster analysis using Rphenograph algorithm (K=30, down-sampled 10000 cells). Nodes significantly enriched in subjects were identified using Kruskal-Wallis rank sum test. 2D heat maps and t-SNE were generated for data visualization.

Results : Subjects with uveitis had a decreased frequency of naïve CD8 T-cells relative to healthy controls, and increased Th22-profile terminally differentiated effector memory (TEMRA) CD4+ T cells with a CCR7-CD27+CD45RA+CD127+IL-22+phenotype. Among AAU patients, those with concurrent AxSpA had a higher frequency of highly differentiated CD8+ TEMRA cells expressing T-bet, granzyme B, perforin, and gut homing chemokine receptor CCR9. Increased T-bet and GATA3 expression in CD4+effector memory T cells was also observed in this group. Manual gating confirmed these findings. (All results Mann-Whitney P<0.05)

Conclusions : Our findings implicate immune activation of T cells with mucosal origin (Th22 cells) in AAU pathogenesis. In those with concurrent systemic inflammatory disease (AxSpA), expression of CCR9 implicates intestinally-derived immune cells in pathogenesis and is accompanied by a Th1 cytotoxic T cell signature.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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