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

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.

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Intra-ocular dendritic cells are increased in HLA-B27 associated acute anterior uveitis

10.1101/2021.02.16.431370 ◽

2021 ◽

Author(s):

Maren Kasper ◽

Michael Heming ◽

David Schafflick ◽

Xiaolin Li ◽

Tobias Lautwein ◽

...

Keyword(s):

Dendritic Cells ◽

Anterior Uveitis ◽

Plasma Cells ◽

Cell Communication ◽

Hla B27 ◽

Acute Anterior Uveitis ◽

Single Cell Rna Sequencing ◽

Infectious Endophthalmitis ◽

Local Cell

AbstractUveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. HLA-B27-associated uveitis is a common subtype of uveitis and a prototypical ocular autoimmune 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 and negative anterior uveitis and an infectious endophthalmitis control by combining single cell RNA-sequencing (scRNA-seq) with flow cytometry and low-input proteomics. Ocular cell infiltrates consisted primarily of lymphocytes in uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27 positive uveitis exclusively featured an plasmacytoid and classical dendritic cells (cDC) infiltrate, and of plasma cells. Moreover, cDCs were central in predicted local cell-cell communication.The data suggests a unique pattern of ocular leukocyte infiltration in HLA-B27 positive uveitis with relevance of particular dendritic cells.

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HLA-B27 frequency in Greek patients with acute anterior uveitis.

British Journal of Ophthalmology ◽

10.1136/bjo.61.11.699 ◽

1977 ◽

Vol 61 (11) ◽

pp. 699-701 ◽

Cited By ~ 15

Author(s):

J Zervas ◽

G Tsokos ◽

G Papadakis ◽

E Kabouklis ◽

D Papadopoulos

Keyword(s):

Anterior Uveitis ◽

Hla B27 ◽

Acute Anterior Uveitis

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Serum Levels of β2-Microglobulin in HLA-B27+Patients with Acute Anterior Uveitis and Ankylosing Spondylitis

Scandinavian Journal of Rheumatology ◽

10.3109/03009749009097068 ◽

1990 ◽

Vol 19 (sup87) ◽

pp. 104-107 ◽

Cited By ~ 2

Author(s):

M. F. C. Beersma ◽

P. J. F. M. Derhaag ◽

T. E. W. Feltkamp

Keyword(s):

Ankylosing Spondylitis ◽

Anterior Uveitis ◽

Serum Levels ◽

Hla B27 ◽

Acute Anterior Uveitis ◽

Β2 Microglobulin

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Is a positive family history of spondyloarthritis relevant for diagnosing axial spondyloarthritis once HLA-B27 status is known?

Rheumatology ◽

10.1093/rheumatology/kez095 ◽

2019 ◽

Vol 58 (9) ◽

pp. 1649-1654 ◽

Cited By ~ 7

Author(s):

Miranda van Lunteren ◽

Désirée van der Heijde ◽

Alexandre Sepriano ◽

Inger J Berg ◽

Maxime Dougados ◽

...

Keyword(s):

Back Pain ◽

Family History ◽

Anterior Uveitis ◽

Chronic Back Pain ◽

Axial Spondyloarthritis ◽

Positive Family History ◽

Hla B27 ◽

Acute Anterior Uveitis ◽

Negative Results ◽

History Of

Abstract Objectives A positive family history (PFH) of spondyloarthritis, in particular a PFH of AS or acute anterior uveitis, is associated with HLA-B27 carriership in chronic back pain patients. As it is unknown, the study aimed to investigate if a PFH contributes to diagnosing axial spondyloarthritis (axSpA) once HLA-B27 status is known. Methods In axSpA-suspected patients from the Assessment of SpondyloArthritis international Society (ASAS), DEvenir des Spondyloarthropathies Indifférenciéés Récentes (DESIR) and SPondyloArthritis Caught Early (SPACE) cohorts, logistic regression analyses were performed with HLA-B27 status and PFH according to the ASAS definition (ASAS-PFH) as determinants and clinical axSpA diagnosis as outcome at baseline. Analyses were repeated with a PFH of AS or acute anterior uveitis. Results In total, 1818 patients suspected of axSpA were analysed (ASAS n = 594, DESIR n = 647, and SPACE n = 577). In patients from the ASAS, DESIR and SPACE cohorts, respectively 23%, 39% and 38% had an ASAS-PFH, 52%, 58% and 43% were HLA-B27 positive, and 62%, 47% and 54% were diagnosed with axSpA. HLA-B27 was independently associated with an axSpA diagnosis in each cohort but an ASAS-PFH was not [ASAS cohort: HLA-B27 odds ratio (OR): 6.9 (95% CI: 4.7, 10.2), ASAS-PFH OR: 0.9 (95% CI: 0.6, 1.4); DESIR: HLA-B27 OR: 2.1 (95% CI: 1.5, 2.9), ASAS-PFH OR: 1.0 (95% CI 0.7, 1.3); SPACE: HLA-B27 OR: 10.4 (95% CI: 6.9, 15.7), ASAS-PFH OR: 1.0 (95% CI: 0.7, 1.5)]. Similar negative results were found for PFH of AS and acute anterior uveitis. Conclusion In three independent cohorts with different ethnical backgrounds, ASAS, DESIR and SPACE, a PFH was not associated independently of HLA-B27 with a diagnosis of axSpA. This indicates that in the vast majority of patients presenting with back pain, a PFH does not contribute to the likelihood of an axSpA diagnosis if HLA-B27 status is known.

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