DNA 5-Hydroxymethylcytosine Landscape and Transcriptional Profile Highlight the TUBB4B-Mediated Th17/Th1/Treg Imbalance in Behçet's Uveitis.

Purpose: Behçet's uveitis (BU) is an auto-inflammatory disease frequently with a poor prognosis. Here, we performed an integrated analysis of DNA 5-hydroxymethylcytosine (5-hmC) landscape and transcriptomic profiling in CD4+ T cells from active BU patients and healthy controls.

Methods: We conducted an integrated analysis of DNA 5-hmC modifications and transcriptomic data from CD4+ T cells of active BU patients and healthy individuals.

Ocular Hypertension or Glaucoma Risk Factor Prediction Models for Patients with Fuchs Uveitis Syndrome.

Purpose: Fuchs uveitis syndrome (FUS) is a chronic inflammatory disorder that can lead to ocular hypertension (OHT)/glaucoma. We aimed to investigate the risk factors for OHT/glaucoma and develop prediction models for these complications in patients with FUS.

Methods: Patients with FUS being referred to the uveitis centre at the First Affiliated Hospital of Chongqing Medical University between April 2008 and March 2023 were enrolled and divided into training and test sets in a 7:3 ratio.

Association of exposure to urinary and blood heavy metals with visual disability among U.S. adults in NHANES 2013-2018.

Background: Heavy metals exposure has been widely referred to as a risk factor for human health. However, studies on the potential impact of heavy metals on visual disability are limited. Herein, this study aims to investigate the associations of urinary and blood heavy metals with visual disability in adults.

Proteomic Profiles of Neutrophils from Behcet's Uveitis Patients and their Sex Differences.

Behcet's uveitis (BU) is one of the most vision-threatening uveitis entities with male-biased incidence and severity. Neutrophil dysfunction has been implicated in the pathogenesis of this disease. However, their proteomic changes are not completely understood.

Association of IL-23/IL-17 Pathway-Related Gene Polymorphisms with Idiopathic Scleritis in Chinese Han Population.

Purpose: To examine the relationship between IL-23/IL-17 pathway gene polymorphisms and scleritis susceptibility in the Chinese Han population.

Methods: We assessed IL-23/IL-17 pathway-related SNPs in 898 scleritis cases and 1,573 controls, employing stratified analysis to evaluate subtype-specific impacts and a discovery-validation cohort strategy to ensure genetic association reliability.

Results: IL-23 R/rs10789229 TC genotype and C allele, and the IL-21/rs2221903 TT genotype and T allele were more frequent in scleritis patients (Pc = 2.

Identification of Subtypes of Herpetic Anterior Uveitis and Characterization of Their Clinical Features and Visual Outcome in a Chinese Population.

Purpose: To identify the subtypes among patients clinically diagnosed as herpetic anterior uveitis (HAU) and characterize their clinical features and visual prognosis.

Methods: Three hundred and seventeen patients were clinically diagnosed as HAU in our department. Aqueous humor (AqH) and serum were collected from 43 of 317 HAU patients during eye surgery.

Identifying prioritization of therapeutic targets for ankylosing spondylitis: a multi-omics Mendelian randomization study.

Background: To investigate the associations of methylation, expression, and protein quantitative trait loci (mQTL, eQTL, and pQTL) with ankylosing spondylitis (AS) and find out genetically supported drug targets for AS.

Methods: The summary-data-based Mendelian randomization (SMR) and Bayesian co-localization analysis were used to assess the potential causality between AS and relevant genes. The GWAS data obtained from the International Genetics of Ankylosing Spondylitis Consortium (IGAS) were set as the discovery stage, and the FinnGen and UK Biobank databases were used to replicate the analysis as an external validation.

Cyclosporin A as an adjunct may enhance the therapeutic effect of interferon alpha-2a in patients with refractory Behcet's uveitis: a retrospective cohort study.

Background: The application of biologic agents has benefited patients with Behcet's uveitis (BU) who do not respond to conventional treatment regimens. However, there is currently no consensus on the optimal treatment regimen of interferon alpha-2a (IFN-α2a) for refractory BU.

Objectives: To evaluate treatment outcomes and safety of IFN-α2a in a large series of refractory BU patients and to explore whether nonbiologic immunomodulatory agents (cyclosporin A) other than corticosteroids should be concomitantly used.

Sensitive optical coherence tomography angiography parameters detecting retinal vascular changes in Behcet's uveitis.

Purpose: To compare the retinal parameters in Behcet's uveitis (BU) patients with wide-field swept-source optical coherence tomography angiography (SS-OCTA) and find a sensitive OCTA parameter.

Methods: Fifty-two eyes from 52 quiescent BU patients and 50 healthy eyes were included. All subjects underwent SS-OCTA examinations with 12 × 12 mm region.

Sex-specific circulating unconventional neutrophils determine immunological outcome of auto-inflammatory Behçet's uveitis.

Neutrophils are the most abundant immune cells that first respond to insults in circulation. Although associative evidence suggests that differences in neutrophils may be linked to the sex-specific vulnerability of inflammatory diseases, mechanistic links remain elusive. Here, we identified extensive sex-specific heterogeneity in neutrophil composition under normal and auto-inflammatory conditions at single-cell resolution.

Clinical characteristics of viral-associated Fuchs uveitis syndrome and Posner-Schlossman syndrome in a Chinese population.

Purpose: To identify the types of viral infection in aqueous humor (AqH) among patients diagnosed as Fuchs uveitis syndrome (FUS) or Posner-Schlossman syndrome (PSS) and investigate their relevance to clinical manifestations and visual outcome.

Methods: A total of 375 patients and 171 patients were diagnosed as FUS or PSS in our department. AqH and serum samples from 68 FUS patients and 16 PSS patients were obtained during eye surgery.

Revealing Academic Evolution and Frontier Pattern in the Field of Uveitis Using Bibliometric Analysis, Natural Language Processing, and Machine Learning.

Purpose: Numerous uveitis articles were published in this century, underneath which hides valuable intelligence. We aimed to characterize the evolution and patterns in this field.

Methods: We divided the 15,994 uveitis papers into four consecutive time periods for bibliometric analysis, and applied latent Dirichlet allocation topic modeling and machine learning techniques to the latest period.

Plasma-derived exosomal protein SHP2 deficiency induces neutrophil hyperactivation in Behcet's uveitis.

To investigate the effect of plasma-derived exosomal proteins on neutrophil hyperactivation in Behcet's uveitis (BU), we treated neutrophils from healthy controls with plasma-derived exosomes from active BU patients, and determined the level of neutrophil activation by real-time quantitative PCR (RT-qPCR) and cytokine detection assay. The results revealed that exosomes from active BU patients could activate neutrophils as shown by increasing the expression levels of pro-inflammatory cytokines (IL-17 and IL-6), chemokines (IL-8 and MCP-1), and NETs (MPO and ELANE). Label-free quantitative proteomic analysis of plasma-derived exosomes from patients and healthy controls found a remarkably distinct protein profile and identified differentially expressed proteins (DEPs) between the two groups.

4-Octyl Itaconate Inhibits Proinflammatory Cytokine Production in Behcet's Uveitis and Experimental Autoimmune Uveitis.

4-octyl itaconate (4-OI) is an anti-inflammatory metabolite that activates the nuclear-factor-E2-related factor 2 (NRF2) signaling. In the current work, we investigated whether 4-OI could affect the production of proinflammatory cytokines in Behcet's uveitis (BU) and experimental autoimmune uveitis (EAU). Peripheral blood mononuclear cells (PBMCs) of active BU patients and healthy individuals with in vitro 4-OI treatment were performed to assess the influence of 4-OI on the proinflammatory cytokine production.

OR11H1 Missense Variant Confers the Susceptibility to Vogt-Koyanagi-Harada Disease by Mediating Gadd45g Expression.

Vogt-Koyanagi-Harada (VKH) disease is a severe autoimmune disease. Herein, whole-exome sequencing (WES) study are performed on 2,573 controls and 229 VKH patients with follow-up next-generation sequencing (NGS) in a collection of 2,380 controls and 2,278 VKH patients. A rare c.

Molecular diagnostic yield for Blau syndrome in previously diagnosed juvenile idiopathic arthritis with uveitis or cutaneous lesions.

Objective: Diagnostic pitfalls often arise in the community because of potentially misleading similarities between juvenile idiopathic arthritis (JIA) and Blau syndrome, an immune-related disorder caused by NOD2 gene mutations. It remains unclear in which population and to what extent next-generation sequencing techniques can aid in diagnosis.

Methods: We evaluated clinical usefulness of targeted next-generation sequencing in previously diagnosed JIA.

A de novo missense mutation in MPP2 confers an increased risk of Vogt-Koyanagi-Harada disease as shown by trio-based whole-exome sequencing.

Vogt-Koyanagi-Harada (VKH) disease is a leading cause of blindness in young and middle-aged people. However, the etiology of VKH disease remains unclear. Here, we performed the first trio-based whole-exome sequencing study, which enrolled 25 VKH patients and 50 controls, followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.

IL-8 Triggers Neutrophil Extracellular Trap Formation Through an Nicotinamide Adenine Dinucleotide Phosphate Oxidase- and Mitogen-Activated Protein Kinase Pathway-Dependent Mechanism in Uveitis.

Purpose: To explore the mechanism underlying IL-8-induced neutrophil extracellular trap (NET) formation in patients with ocular-active Behçet's disease (BD) and the effect of inhibiting NET formation on the severity of inflammation in experimental autoimmune uveitis (EAU) mice.

Methods: The serum extracellular DNA and neutrophil elastase (NE) and IL-8 levels in patients with ocular-active BD, the expression of myeloperoxidase, NE, and histone H3Cit in IL-8-induced neutrophils isolated from healthy controls, and the effects of NETs on HMC3 cells were detected. Female C57BL/6J mice were immunized with IRBP651-670 to induce EAU and EAU mice received intravitreal injection of the CXCR2 (IL-8 receptor) antagonist SB225002 or PBS.

Identification of FCER1G as a cyclosporin A plus corticosteroid sensitization gene in female patients with Vogt-Koyanagi-Harada disease.

The resistance development of the combination regimen of corticosteroids (CS) with cyclosporin A (CsA) leads to therapeutic failure of some patients with autoimmune diseases. In the male patients with Vogt-Koyanagi-Harada (VKH) disease, we have identified RPS4Y1 as an important resistance gene of the regimen and a functional mediator of chlorambucil (CLB). However, it remains unclear what is responsible for the resistance in female patients.

Comprehensive evaluation of functional vision, quality of life, and cognitive ability in pediatric uveitis.

Background: Pediatric uveitis may cause severe impairment of vision in children and affect their quality of life as well as cognitive ability. This study aims to evaluate the functional vision, visual-related and health-related quality of life, and cognitive ability in pediatric uveitis.

Methods: Children with uveitis aged 5-16 years old completed six validated instruments to assess functional visual ability with Cardiff Visual Ability Questionnaire for Children (CVAQC), vision-related quality of life with Impact of Vision Impairment for Children (IVI-C), health-related quality of life with Pediatric Quality of Life Inventory (PedsQL), cognitive ability with Chinese Wechsler Intelligence Scale for Children (C-WISC), and depression and anxiety evaluation with Hospital Anxiety and Depression Scale (HAD).

Epigenome-wide association study identifies Vogt-Koyanagi-Harada disease-associated DNA methylation loci in Chinese.

DNA methylation is one of the important epigenetic mechanisms for modulating gene expression. By performing a genome-wide methylation association analysis of whole peripheral blood from 60 Vogt-Koyanagi-Harada disease (VKH) patients and 60 healthy controls, we depicted the global DNA methylation status of VKH disease. Further pyrosequencing validation in 160 patients and 159 controls identified 3 aberrant CpG sites in HLA gene regions including cg04026937 and cg18052547 (located in HLA-DRB1 region), and cg13778567 (HLA-DQA1).