Recent Developments in HLA B27 Anterior Uveitis

Wakefield, Denis; Clarke, Daniel; McCluskey, Peter

doi:10.3389/fimmu.2020.608134

Cited by 43 publications

(29 citation statements)

References 85 publications

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“…One extension of the present study will be to define the responses of stroma 1 and stroma 2 cells to inflammation. Iris inflammation (iritis) is one component of anterior segment uveitis, a common autoimmune condition ( Martin et al, 2002 ; Artornsombudh et al, 2014 ; Wakefield et al, 2020 ). Work in a variety of disease contexts has shown that stromal cells change their patterns of gene expression in response to inflammation and that they can epigenetically ‘remember’ prior bouts of inflammation ( Neumann et al, 2010 ; Crowley et al, 2018 ; Mizoguchi et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

A transcriptome atlas of the mouse iris at single-cell resolution defines cell types and the genomic response to pupil dilation

Wang

Rattner

Nathans

2021

eLife

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The iris controls the level of retinal illumination by controlling pupil diameter. It is a site of diverse ophthalmologic diseases and it is a potential source of cells for ocular auto-transplantation. The present study provides foundational data on the mouse iris based on single nucleus RNA sequencing. More specifically, this work has (1) defined all of the major cell types in the mouse iris and ciliary body, (2) led to the discovery of two types of iris stromal cells and two types of iris sphincter cells, (3) revealed the differences in cell type-specific transcriptomes in the resting vs. dilated states, and (4) identified and validated antibody and in situ hybridization probes that can be used to visualize the major iris cell types. By immunostaining for specific iris cell types, we have observed and quantified distortions in nuclear morphology associated with iris dilation and clarified the neural crest contribution to the iris by showing that Wnt1-Cre-expressing progenitors contribute to nearly all iris cell types, whereas Sox10-Cre-expressing progenitors contribute only to stromal cells. This work should be useful as a point of reference for investigations of iris development, disease, and pharmacology, for the isolation and propagation of defined iris cell types, and for iris cell engineering and transplantation.

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Section: Discussionmentioning

confidence: 99%

A transcriptome atlas of the mouse iris at single-cell resolution defines cell types and the genomic response to pupil dilation

Wang

Rattner

Nathans

2021

eLife

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“…Although the exact pathogenesis of AU remains unclear, largescale genome wide association studies have confirmed that AU is a polygenic disease, with overlaps with the seronegative arthropathies and inflammatory bowel diseases, associations that have been repeatedly confirmed in clinical studies (Wakefield et al, 2020). Some evidence has proven that epigenetic modifications are involved in the regulation of AU development, such as microRNAs.…”

Section: Epigenetic Modifications and Anterior Uveitismentioning

confidence: 99%

“…In severe forms of acute AU (AAU), hypopyon and fibrin can be visualized as a white and dense clot in the anterior chamber ( Agrawal et al, 2010 ). In addition, approximately 50% of all patients with acute AU (AAU) are human leukocyte antigen B27 (HLA B27) positive ( Wakefield et al, 2020 ). Some authors speculate on the prognosis of HLA-B27-related AAU, reporting a higher frequency of recurrence and a worse outcome than HLA-B27-negative AAU ( Rothova et al, 1987 ; Power et al, 1998 ).…”

Section: Epigenetic Modifications In Different Types Of Uveitismentioning

confidence: 99%

Epigenetic Modifications and Therapy in Uveitis

Zou

Xue

et al. 2021

Front. Cell Dev. Biol.

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Uveitis is a sight-threatening intraocular inflammation, and the exact pathogenesis of uveitis is not yet clear. Recent studies, including multiple genome-wide association studies (GWASs), have identified genetic variations associated with the onset and progression of different types of uveitis, such as Vogt–Koyanagi–Harada (VKH) disease and Behcet’s disease (BD). However, epigenetic regulation has been shown to play key roles in the immunoregulation of uveitis, and epigenetic therapies are promising treatments for intraocular inflammation. In this review, we summarize recent advances in identifying epigenetic programs that cooperate with the physiology of intraocular immune responses and the pathology of intraocular inflammation. These attempts to understand the epigenetic mechanisms of uveitis may provide hope for the future development of epigenetic therapies for these devastating intraocular inflammatory conditions.

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“…HLA-B27 is associated with the development of common inflammatory rheumatic diseases such as the spondyloarthritides (SPA), ankylosing spondylitis (AS), and reactive arthritis [102]. HLA-B27 is also associated with inflammatory eye disease, anterior uveitis [103]. HLA-B27 is devoid of β2m and HLA-II in a transgenic mouse model that develops arthritis.…”

Section: Face-3 Of Hla-b27mentioning

confidence: 99%

Four Faces of Cell-Surface HLA Class-I: Their Antigenic and Immunogenic Divergence Generating Novel Targets for Vaccines

Ravindranath

Selvan

et al. 2022

Vaccines

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Leukocyte cell-surface HLA-I molecules, involved in antigen presentation of peptides to CD8+ T-cells, consist of a heavy chain (HC) non-covalently linked to β2-microglobulin (β2m) (Face-1). The HC amino acid composition varies across all six isoforms of HLA-I, while that of β2m remains the same. Each HLA-allele differs in one or more amino acid sequences on the HC α1 and α2 helices, while several sequences among the three helices are conserved. HCs without β2m (Face-2) are also observed on human cells activated by malignancy, viral transformation, and cytokine or chemokine-mediated inflammation. In the absence of β2m, the monomeric Face-2 exposes immunogenic cryptic sequences on these cells as confirmed by HLA-I monoclonal antibodies (LA45, L31, TFL-006, and TFL-007). Furthermore, such exposure enables dimerization between two Face-2 molecules by SH-linkage, salt linkage, H-bonding, and van der Waal forces. In HLA-B27, the linkage between two heavy chains with cysteines at position of 67 of the amino acid residues was documented. Similarly, several alleles of HLA-A, B, C, E, F and G express cysteine at 67, 101, and 164, and additionally, HLA-G expresses cysteine at position 42. Thus, the monomeric HC (Face-2) can dimerize with another HC of its own allele, as homodimers (Face-3), or with a different HC-allele, as heterodimers (Face-4). The presence of Face-4 is well documented in HLA-F. The post-translational HLA-variants devoid of β2m may expose several cryptic linear and non-linear conformationally altered sequences to generate novel epitopes. The objective of this review, while unequivocally confirming the post-translational variants of HLA-I, is to highlight the scientific and clinical importance of the four faces of HLA and to prompt further research to elucidate their functions and their interaction with non-HLA molecules during inflammation, infection, malignancy and transplantation. Indeed, these HLA faces may constitute novel targets for passive and active specific immunotherapy and vaccines.

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Recent Developments in HLA B27 Anterior Uveitis

Cited by 43 publications

References 85 publications

A transcriptome atlas of the mouse iris at single-cell resolution defines cell types and the genomic response to pupil dilation

A transcriptome atlas of the mouse iris at single-cell resolution defines cell types and the genomic response to pupil dilation

Epigenetic Modifications and Therapy in Uveitis

Four Faces of Cell-Surface HLA Class-I: Their Antigenic and Immunogenic Divergence Generating Novel Targets for Vaccines

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