Intraocular dendritic cells characterize HLA-B27-associated acute anterior uveitis.

Maren Kasper,Michael Heming,Tobias Lautwein,Dirk Bauer,David Schafflick,Heinz Wiendl,Karin Loser,Melissa Meyer Zu Horste,Karoline Walscheid,Gerd Meyer Zu Hörste,Arnd Heiligenhaus,Xiaolin Li

doi:10.7554/elife.67396

Abstract

Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. Uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27-positive (n = 4) and -negative (n = 2) anterior uveitis and an infectious endophthalmitis control (n = 1) by combining single-cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27-positive uveitis exclusively featured a plasmacytoid and classical dendritic cell (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27-positive uveitis with relevance to DCs.

Highlights

Uveitis describes a heterogeneous group of inflammatory diseases involving uveal tissues in the intraocular cavity of the eye
We found that lymphocytes predominate in the intraocular infiltrate in B27+ Acute anterior uveitis (AAU) and showed an elevated frequency of plasmacytoid dendritic cells (DCs) and classical DCs
We here aimed for an unbiased characterization of leukocytes in the aqueous humor (AqH) in Anterior uveitis (AU) flares

Summary

Introduction

Uveitis describes a heterogeneous group of inflammatory diseases involving uveal tissues in the intraocular cavity of the eye. Non-infectious uveitis is regarded as an autoimmune disorder and is associated with various immune-m ediated systemic diseases. Its typical clinical features include acute onset of discomfort, eye redness, tearing, visual impairment, and excessive cellular infiltration in the aqueous humor (AqH; ie, the intraocular liquid of the anterior chamber) that is devoid of immune cells under non-d iseased conditions. The prevalence of the HLA-B27 haplotype is approximately 8–10% among Caucasians and 40–70% among AAU patients (Kopplin et al, 2016) and represents a strong genetic risk factor for AAU (Brewerton et al, 1973; Huhtinen and Karma, 2000). The HLA-B27 allele conveys an increased genetic risk for other immune-m ediated diseases, including spondyloarthropathies (SpA)

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Discussion

Conclusion