Autoimmunity, Autoinflammation, and Infection in Uveitis

Forrester, John V.; Kuffová, Lucia; Dick, Andrew D.

doi:10.1016/j.ajo.2018.02.019

Cited by 117 publications

(108 citation statements)

References 97 publications

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“…The pathogenic mechanisms underlying NIU remain incompletely understood, but are certainly immune-mediated ( 13 , 29 ). In humans, multiple lines of evidence have linked type 17 immune responses (e.g., IL-17-producing T cells) to NIU ( 11 , 12 , 14 , 30 – 33 ).…”

Section: Discussionmentioning

confidence: 99%

High-Dimensional Profiling Reveals Heterogeneity of the Th17 Subset and Its Association With Systemic Immunomodulatory Treatment in Non-infectious Uveitis

et al. 2018

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Background: Non-infectious uveitis (NIU) is a severe intra ocular inflammation, which frequently requires prompt systemic immunosuppressive therapy (IMT) to halt the development of vision-threatening complications. IMT is considered when NIU cannot be treated with corticosteroids alone, which is unpredictable in advance. Previous studies have linked blood cell subsets to glucocorticoid sensitivity, which suggests that the composition of blood leukocytes may early identify patients that will require IMT.Objective: To map the blood leukocyte composition of NIU and identify cell subsets that stratify patients that required IMT during follow-up.Methods: We performed controlled flow cytometry experiments measuring a total of 37 protein markers in the blood of 30 IMT free patients with active non-infectious anterior, intermediate, and posterior uveitis, and compared these to 15 age and sex matched healthy controls. Results from manual gating were validated by automatic unsupervised gating using FlowSOM.Results: Patients with uveitis displayed lower relative frequencies of Natural Killer cells and higher relative frequencies of memory T cells, in particular the CCR6+ lineages. These results were confirmed by automatic gating by unsupervised clustering using FlowSOM. We observed considerable heterogeneity in memory T cell subsets and abundance of CXCR3-CCR6+ (Th17) cells between the uveitis subtypes. Importantly, regardless of the uveitis subtype, patients that eventually required IMT in the course of the study follow-up exhibited increased CCR6+ T cell abundance before commencing therapy.Conclusion: High-dimensional immunoprofiling in NIU patients shows that clinically distinct forms of human NIU exhibit shared as well as unique immune cell perturbations in the peripheral blood and link CCR6+ T cell abundance to systemic immunomodulatory treatment.

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Section: Discussionmentioning

confidence: 99%

High-Dimensional Profiling Reveals Heterogeneity of the Th17 Subset and Its Association With Systemic Immunomodulatory Treatment in Non-infectious Uveitis

et al. 2018

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“…Retinal autoimmunity has been proposed in TB-associated uveitis for a while. 18,19 Moreover, the development of anterior granulomatous uveitis has been described following Bacille-Calmette-Guérin (BCG) therapy for bladder carcinoma. This was associated with the presence of peripheral T-cells that proliferated and produced cytokines (a.o.…”

Section: Discussionmentioning

confidence: 99%

No Evidence for Circulating Retina Specific Autoreactive T-cells in Latent Tuberculosis-associated Uveitis and Sarcoid Uveitis

Schrijver

Hardjosantoso

Berge

et al. 2020

Ocular Immunology and Inflammation

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Purpose: To detect circulating retina-specific autoreactive CD4 + T-cells and antiretinal antibodies (ARA) in latent tuberculosis (TB)-associated uveitis or sarcoid uveitis patients. Methods: The presence of crude retinal extract (RE) autoreactive CD4 + T-cells was determined by a highly sensitive flowcytometric-based technique examining co-expression of CD25 and CD134 (OX40) on RE stimulated PBMC. The presence of ARA in available matched serum samples was assessed by indirect immunofluorescence. Results: No autoreactive CD4 + T-cells against RE could be detected in either latent TB-associated uveitis or sarcoid uveitis patients, while ARA were detected in the serum of the majority (5/6) of latent TBassociated uveitis and all (3/3) sarcoid uveitis patients. Conclusion: Even with the use of this highly sensitive flowcytometric technique circulating retinaspecific autoreactive CD4 + T-cells could not be detected. In contrast, ARA were detected in the majority of patients indicating an adaptive humoral immune response toward retinal antigens had occurred.

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“…As in uveitis, Forrester et al agreed that infection may directly or indirectly related to noninfectious uveitis in the eye. 21 In this consideration, remind us that infection might be a potential cause of PVR.…”

Section: Discussionmentioning

confidence: 99%

Expression Profile of Peripheral Immune Cells-derived Coding and Long Non-coding RNAs in Patients With Proliferative Vitreoretinopathy

Ni¹,

Liu²,

Hu³

et al. 2020

Preprint

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Introduction: Peripheral immune response has been revealed to play a critical role in proliferative vitreoretinopathy (PVR). However, the reliable immune-related factors that are acting as prognostic indicators or therapeutic targets for PVR remain to explore further.Methods: In the current study, we applied whole-transcriptome sequencing to profile peripheral blood mononuclear cells (PBMCs) from PVR patients and also analyzed lncRNA-mRNA interactions in peripheral immune cells to explore the pathways that might mediate immunopathology and resultant retinal damage in PVR. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and Ingenuity Pathway Analysis (IPA) were employed to classify the function of these differentially expressed genes (DEGs).Results: Compared to the controls, there were 319 genes upregulated, and 191 genes downregulated in PVR patients. GO, and KEGG enrichment analyses as well as IPA showed that these upregulated genes were significantly enriched in immune-related and infection-relate terms. Immune-related gene NFKBIA, CXCL2, and CXCL8 were detected as hub-genes in the co-expression network, while lncRNAs such as AC007032.1, AC037198.2, AL929472.2, and SLED1 were highly co-expressed with them. lncRNA-mRNA interactions analysis also showed that putative targeted genes of these differentially expressed lncRNAs were also significantly enriched in immune-related or infection-relate pathways.Conclusion: Our study highlights the transformation of immune-related genes/pathways in PVR by comparing controls, and validates several critical genes and lncRNAs, which are serving as potential diagnostic markers for PVR patients.

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Autoimmunity, Autoinflammation, and Infection in Uveitis

Cited by 117 publications

References 97 publications

High-Dimensional Profiling Reveals Heterogeneity of the Th17 Subset and Its Association With Systemic Immunomodulatory Treatment in Non-infectious Uveitis

High-Dimensional Profiling Reveals Heterogeneity of the Th17 Subset and Its Association With Systemic Immunomodulatory Treatment in Non-infectious Uveitis

No Evidence for Circulating Retina Specific Autoreactive T-cells in Latent Tuberculosis-associated Uveitis and Sarcoid Uveitis

Expression Profile of Peripheral Immune Cells-derived Coding and Long Non-coding RNAs in Patients With Proliferative Vitreoretinopathy

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Autoimmunity, Autoinflammation, and Infection in Uveitis

Cited by 117 publications

References 97 publications

High-Dimensional Profiling Reveals Heterogeneity of the Th17 Subset and Its Association With Systemic Immunomodulatory Treatment in Non-infectious Uveitis

High-Dimensional Profiling Reveals Heterogeneity of the Th17 Subset and Its Association With Systemic Immunomodulatory Treatment in Non-infectious Uveitis

No Evidence for Circulating Retina Specific Autoreactive T-cells in Latent Tuberculosis-associated Uveitis and Sarcoid Uveitis

Expression Profile of Peripheral Immune Cells-derived Coding and Long Non-coding RNAs&nbsp;in Patients With Proliferative Vitreoretinopathy

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Expression Profile of Peripheral Immune Cells-derived Coding and Long Non-coding RNAs in Patients With Proliferative Vitreoretinopathy