Gut microbial signatures and their functions in Behcet's uveitis and Vogt-Koyanagi-Harada disease.

Background: A number of public metagenomic studies reveal an association between the gut microbiome and various immune-mediated diseases including Behcet's uveitis (BU) and Vogt-Koyanagi-Harada disease (VKH). Integrated-analysis and subsequent validation of these results could be a potentially powerful way to understand the microbial signatures and their functions in these two uveitis entities.

Methods: We integrated the sequencing data of our previous metagenomic studies on two major uveitis entities, BU and VKH as well as four other publicly available immune-mediated diseases datasets, including Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Crohn's disease (CD) and Ulcerative Colitis (UC).

NLRP3 Attenuates Intraocular Inflammation by Inhibiting AIM2-Mediated Pyroptosis Through the Phosphorylated Salt-Inducible Kinase 1/Sterol Regulatory Element Binding Transcription Factor 1 Pathway.

Objective: The NLRP3 inflammasome has been shown to be involved in the development of uveitis, but the exact mechanism remains elusive. This study was undertaken to explore the role of NLRP3 in the development of uveitis.

Methods: First, Nlrp3-deficient mice were used to study the role of NLRP3 in experimental autoimmune diseases, such as experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE).

Identification of differently expressed mRNAs by peripheral blood mononuclear cells in Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada disease (VKH) is a rare autoimmune disease characterized by diffuse and bilateral uveitis, alopecia, tinnitus, hearing loss, vitiligo and headache. The transcriptional expression pattern of peripheral blood mononuclear cells (PBMC) in VKH remains largely unknown. In this study, mRNA sequencing was conducted in PBMC from VKH patients with active uveitis before treatment ( = 7), the same patients after prednisone combined with cyclosporine treatment ( = 7) and healthy control subjects strictly matched with gender and age ( = 7).

Genetically predicted fasting blood glucose level plays a causal role in intraocular pressure: A Mendelian randomisation study.

Background: This study aimed to examine possible causal associations between various components of metabolic syndrome and glaucoma-related phenotypes.

Methods: A two-sample Mendelian randomisation study was conducted with the models of inverse-variance weighted (IVW), maximum likelihood, weighted median and MR-Egger regression. We accessed data from publicly available genome-wide association studies for individual parameters of metabolic syndrome as the exposures and the data for glaucoma and its endophenotypes as the outcomes.

Optical Coherence Tomographic Features and Prognostic Values of Macular Edema in Vogt-Koyanagi-Harada Disease.

To determine optical coherence tomographic (OCT) features of macular edema (ME) and identify potential prognostic values for ME and visual outcomes in Vogt-Koyanagi-Harada disease (VKH). In the retrospective case series, a total of 1,377 VKH patients who were seen in a tertiary uveitis center between September 2011 and January 2018 were reviewed on their demographics, visual acuity, ocular and extraocular manifestations, modes of treatment, and OCT examinations. Of these patients, 79 (5.

Surveillance of Liver Function in Uveitis with or without Chronic HBV Infection.

Introduction: Immunosuppressive therapy for uveitis may cause liver damage.

Methods: To investigate incidence of liver damage during uveitis treatment, we compared serological Hepatitis B core antibody (HBcAb) status with risk of liver dysfunction in all participants (n = 992), in anterior uveitis (AU) (n = 489), and combined of intermediate, posterior, or panuveitis (IPPU) patients (n = 503). The primary endpoint was incidence of elevated serum alanine aminotransferase level above 2-fold upper limits of normal within 6 months.

Trends in Corneal Transplantation and Characteristics of Donors in the Chongqing Eye Bank, China: A Retrospective Study, 1999-2018.

This study aimed to analyze corneal transplantation trends and voluntary donor characteristics at the Chongqing Eye Bank in China. We retrospectively reviewed and analyzed data from January 1, 1999, to December 31, 2018, covering 5,397 preregistered voluntary donors, 1,955 actual donors, 3,910 donated tissues, and 2,374 corneal transplantations. The 5,397 preregistered donors included 13 ethnic groups, with an overall mean age of 39.

Identification of Novel Risk Loci for Behçet's Disease-Related Uveitis in a Chinese Population in a Genome-Wide Association Study.

Objective: To explore susceptibility loci associated with uveitis in Behçet's disease (BD).

Methods: We conducted a 2-stage study, consisting of a genome-wide association study (GWAS) stage and a replication stage, in a Chinese population. The GWAS stage included 978 cases with BD-related uveitis and 4,388 controls, and the replication stage included 953 cases with BD-related uveitis and 2,129 controls.

SNP-mediated binding of TBX1 to the enhancer element of reduces the risk of Behçet's disease.

The genetic association between Behçet's disease susceptibility and  has been confirmed in multiple cohorts, but the underlying mechanism of this association remains unclear. We combined public resources and laboratory experiments (electrophoretic mobility shift assays, chromatin immunoprecipitation, luciferase reporter gene and CRISPR/Cas9 genome editing) to analyze transcription factor binding and enhancer activity controlling expression. The T allele of noncoding rs3024490 within super-enhancer elements is able to specifically bind TBX1 and, in turn, promotes the enhancer activity and increased expression of .

Changes in the Gut Microbiome Contribute to the Development of Behcet's Disease Adjuvant Effects.

Behcet's disease (BD) is associated with considerable gut microbiome changes. However, it still remains unknown how the composition of the gut microbiome exactly affects the development of this disease. In this study, transplantation of stool samples from patients with active ocular BD to mice oral gavage was performed.

Association between Fine Particulate Air Pollution and the Onset of Uveitis in Mainland China.

Purpose: Although it has long been recognized that air pollution can affect the immune system and human ocular symptoms, it is uncertain whether air pollutants may also contribute to the development of uveitis. This study aimed to quantify the association of particulate matters less than 2.5 μm (PM2.

Development of revised diagnostic criteria for Fuchs' uveitis syndrome in a Chinese population.

Background/aims: Fuchs' uveitis syndrome (FUS) is one of the frequently misdiagnosed uveitis entities, which is partly due to the absence of internationally recognised diagnostic criteria. This study was performed to develop and evaluate a set of revised diagnostic criteria for FUS.

Methods: The clinical data of Chinese patients with FUS and patients with non-FUS were collected and analysed from a tertiary referral centre between April 2008 and December 2020.

Specific sweat metabolite profile in ocular Behcet's disease.

Background: Behcet's disease (BD) is an autoimmune disorder with the serious possibility of blindness, calling for further research on its pathogenesis. Our aim was to study the metabolite composition of sweat in BD and to identify possible biomarkers.

Methods: Metabolomics analysis was performed on sweat samples from 20 BD patients and 18 normal controls by liquid chromatography tandem mass spectrometry.

High Ambient Temperature Aggravates Experimental Autoimmune Uveitis Symptoms.

Whether ambient temperature influences immune responses leading to uveitis is unknown. We thus tested whether ambient temperature affects the symptoms of experimental autoimmune uveitis (EAU) in mice and investigated possible mechanisms. C57BL/6 mice were kept at a normal (22°C) or high temperature (30°C) housing conditions for 2 weeks and were then immunized with human interphotoreceptor retinoid-binding protein (IRBP651-670) peptide to induce EAU.

Metabolomic Analysis of Aqueous Humor Identifies Aberrant Amino Acid and Fatty Acid Metabolism in Vogt-Koyanagi-Harada and Behcet's Disease.

To investigate aqueous metabolic profiles in Vogt-Koyanagi-Harada (VKH) and Behcet's disease (BD), we applied ultra-high-performance liquid chromatography equipped with quadrupole time-of flight mass spectrometry in aqueous humor samples collected from these patients and controls. Metabolite levels in these three groups were analyzed by univariate logistic regression. The differential metabolites were subjected to subsequent pathway analysis by MetaboAnalyst.

Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease.

The diagnosis of Vogt-Koyanagi-Harada (VKH) disease is mainly based on a complex clinical manifestation while it lacks objective laboratory biomarkers. To explore the potential molecular biomarkers for diagnosis and disease activity in VKH, we performed an untargeted urine metabolomics analysis by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Through univariate and multivariate statistical analysis, we found 9 differential metabolites when comparing VKH patients with healthy controls, and 26 differential metabolites were identified when comparing active VKH patients with inactive VKH patients.

The haplotypes of various TNF related genes associated with scleritis in Chinese Han.

Background: Several studies have stated that TNF-α participates in the pathogenesis of scleritis, but also in several systemic autoimmune diseases and vasculitis, of which some are associated with scleritis. Earlier GWAS and SNP studies have confirmed that multiple SNPs of TNF related genes are associated with many immune-mediated disorders. The purpose of this study was to examine the association of TNF related gene polymorphisms with scleritis in Chinese Han.

Linoleic acid inhibits in vitro function of human and murine dendritic cells, CD4T cells and retinal pigment epithelial cells.

Purpose: Increased linoleic acid (LA) was observed in acute anterior uveitis (AAU) patient feces in our previous study. To investigate the immunoregulatory effect of LA, we studied the effect of LA on human and murine dendritic cells (DCs), CD4T cells, and retinal pigment epithelial (RPE) cells in vitro.

Methods: The level of LA in feces from AAU patients and healthy individuals was measured by gas chromatography coupled with a mass spectrometer (GC-MS).

Association between temperature changes and uveitis onset in mainland China.

Background: Some uveitis subtypes show seasonal patterns. Whether these patterns are caused by seasonally varying temperatures or by other climatic factors remains unknown. This ecological research aimed to quantify the association between climate variability and uveitis onset.

Prevalence, risk factors and management of ocular hypertension or glaucoma in patients with Vogt-Koyanagi-Harada disease.

Background/aims: This study was performed to examine the prevalence, risk factors and treatment outcome of OHT/glaucoma in Chinese patients with Vogt-Koyanagi-Harada (VKH).

Methods: Retrospective non-interventional case series were conducted on a total of 2281 patients with VKH referred from April 2008 to April 2019. Of these cases, 1457 had a minimum follow-up period of 3 months and were included for this study.

Small molecules targeting RORγt inhibit autoimmune disease by suppressing Th17 cell differentiation.

Th17 cells, a lymphocyte subpopulation that is characterized by the expression of the transcription factor "retinoic acid receptor-related orphan receptor gamma-t" (RORγt), plays an important role in the pathogenesis of autoimmune disease. The current study was set up to discover novel and non-steroidal small-molecule inverse agonists of RORγt and to determine their effects on autoimmune disease. Structure-based virtual screening (SBVS) was used to find compounds targeting RORγt.

Functional Genetic Polymorphisms in the IL1RL1-IL18R1 Region Confer Risk for Ocular Behçet's Disease in a Chinese Han Population.

Single nucleotide polymorphisms (SNPs) in the IL1RL1-IL18R1 region are associated with various immune-mediated diseases. This study was carried out to investigate the causal variant for ocular Behçet's disease (BD) and elucidate its target genes in the IL1RL1-IL18R1 region. Nine candidate functional SNPs were prioritized with bioinformatics analysis, followed by a two-stage association study in 694 ocular BD patients and 1,458 unaffected controls.

RETINAL VASCULITIS, A COMMON MANIFESTATION OF IDIOPATHIC PEDIATRIC UVEITIS?

Purpose: Pediatric idiopathic uveitis typically shows anterior segment involvement. Whether retinal vasculitis is an important manifestation of this disease remains unknown and was therefore the subject of this study.

Methods: This study was performed involving patients with pediatric idiopathic uveitis.

Plasma metabolomics study of Vogt-Koyanagi-Harada disease identifies potential diagnostic biomarkers.

Vogt-Koyanagi-Harada (VKH) disease is a common type of uveitis in China, but the diagnosis criteria of VKH disease is controversial. The aim of this study was to investigate potential diagnostic plasma biomarkers for VKH disease. A case-control study including 55 VKH patients (28 active patients and 27 inactive VKH patients) and 30 healthy controls in a tertiary referral center was performed.

Increased Expression of Indoleamine 2,3-Dioxygenase (IDO) in Vogt-Koyanagi-Harada (VKH) Disease May Lead to a Shift of T Cell Responses Toward a Treg Population.

Previous studies have pointed out that indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme initiating tryptophan metabolism, plays a role in the regulation of the immune system. This project was designed to investigate the potential role of IDO in monocyte-derived dendritic cells (moDCs) obtained from active Vogt-Koyanagi-Harada (VKH) disease patients. In this study, we found that the IDO mRNA expression and enzyme activity were increased in active VKH patients as compared with healthy controls and patients in remission.