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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. Luciferase reporter analysis and chromatin immunoprecipitation assay were performed to explore the functional role of susceptibility genetic variants near ZMIZ1., Results: Three independent HLA alleles (HLA-B51 [3.75 × 10 -190 ], HLA-A26 [1.50 × 10 -18 ], and HLA-C0704 [3.44 × 10 -16 ]) were identified as having a genome-wide association with BD-related uveitis. In the non-HLA region, in addition to confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta-analysis of the Chinese cohort consisting of 1,931 cases and 6,517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome-wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1-FIBP-FOSL1, and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with enhanced transcription activity and increased expression of ZMIZ1., Conclusion: This GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enrich our understanding of the contribution of genetic factors to the disease., (© 2021 American College of Rheumatology.)

Importance: Although experimental studies support the hypothesis that exposure of infectious agents may trigger an aberrant immune response and contribute to noninfectious uveitis, the association of a definite pathogen with human noninfectious uveitis conditions appears not to have been well established in a population., Objective: To evaluate associations of tuberculosis infection with risk of several noninfectious uveitis conditions., Design, Setting, and Participants: These mendelian randomization and observational analyses were conducted with the genetic data of a Chinese cohort enrolled between April 2008 and January 2018 and a Japanese cohort enrolled between January 2002 and June 2009. We recruited participants for T-SPOT.TB (Oxford Immunotec) assays between July and November 2019. The Chinese cohort included patients with uveitis associated with Behçet disease or other uveitis conditions and control participants. The Japanese cohort and the group given T-SPOT.TB assays included individuals with Behçet disease and control participants. Data analyses for this study were completed from July 2019 to January 2020., Exposures: Genetic variants associated with tuberculosis as natural proxies for tuberculosis exposure., Main Outcomes and Measures: The primary outcome was the odds ratio (OR) for Behçet disease, estimated by an inverse variance weighted mean of associations with genetically determined tuberculosis susceptibility. The T-SPOT.TB positivity rate was examined in individuals with Behçet disease and compared with that of control participants., Results: The Chinese cohort included 999 patients with uveitis associated with Behçet disease, 1585 with other uveitis conditions, and 4417 control participants. The Japanese cohort included 611 individuals with Behçet disease and 737 control participants. The group given T-SPOT.TB assays included 116 individuals with Behçet disease and 121 control participants. Of the Chinese individuals with Behçet disease and control participants, 2257 (41.7%) were female and the mean (SD) age was 35.4 (12.5) years. In the Japanese cohort, 564 (41.8%) were female and the mean (SD) age was 39.1 (12.7) years. Genetically determined tuberculosis susceptibility was associated with an increased risk for Behçet disease. The OR for Behçet disease per 2-fold increase in tuberculosis incidence was 1.26 (95% CI, 1.12-1.43; P = 1.47 × 10-4). Replication using the Japanese cohort yielded similar results (OR, 1.16 [95% CI, 1.08-1.26]). In T-SPOT.TB assays, having a positive result, indicating a history of tuberculosis infection, was found to be an independent risk factor for Behçet disease (OR, 2.26 [95% CI, 1.11-4.60])., Conclusions and Relevance: These human genetic and biomarker data demonstrated that tuberculosis exposure was a risk factor for Behçet disease. This study provides novel evidence linking an infectious agent to the risk of a noninfectious uveitis condition.

Purpose: To characterise the ocular and extraocular findings in patients with relapsing polychondritis (RP) patients., Design: Retrospective, longitudinal study., Methods: A total number of 16 patients with ocular RP, seen in our tertiary uveitis referral centre over a time period of 10 years were included in this study. Routine ocular examinations such as best-corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, ophthalmoscopy and auxiliary examinations including ultrasound biomicroscopy, B-scanultrasonography, fundus fluorescein angiography and optical coherence tomography were performed. Ocular and systemic manifestations of these 16 patients were analysed and compared with those presented by others. The patients were treated by corticosteroids or in combination with immunosuppressive agents., Results: Eleven male and five female patients were included with a mean age of 40.4 years. Ocular involvement was bilateral in 75% of the patients and manifested as scleritis (n=10) or uveitis (n=6). Generalised, anterior and posterior uveitis was found in three, two and one patients, respectively. The frequencies of inner ear involvement and arthritis were lower in Chinese patients compared with that observed in Caucasians. Nine patients had a follow-up of 2-44 months, and in these individuals a better visual prognosis was observed in female patients compared with males., Conclusions: Our study shows that uveitis associated with RP may manifest as generalised, anterior or posterior uveitis. The incidence of inner ear involvement and arthritis in these patients was lower than that in Caucasians. Female patients seem to have milder inflammation and a better visual prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the clinical features of 51 uveitis patients with psoriasis in China., Methods: The psoriasis type, demographics, ocular findings, auxiliary examination findings, complications, and therapeutic effects were analyzed., Results: A total of 37 male and 14 female uveitis patients with psoriasis were classified into four groups: psoriasis vulgaris (29 cases); psoriatic arthritis (15 cases); psoriatic erythroderma (6 cases); and pustular psoriasis (1 case). The onset age of psoriasis was younger than for uveitis (p < 0.001). Anterior uveitis, panuveitis, and posterior uveitis was observed in 58.8%, 35.3%, and 5.9% of the patients, respectively. Hypopyon was more frequently noted in the group with psoriatic arthritis (p = 0.007). Optic disc staining was more frequently noted in the group with psoriatic erythroderma (p = 0.029). Significant visual improvement was observed in 17 patients., Conclusions: Uveitis can be associated with various types of psoriasis in China, but was most frequently observed in patients with psoriasis vulgaris and psoriatic arthritis.

Background: MicroRNA-146a (miR-146a) was a key negative regulator of autoimmunity. V-Ets oncogene homolog 1 (Ets-1) was demonstrated to bind to the miR-146a promoter region and markedly affects miR-146a promoter activity. This study aimed to investigate the association of miR-146a and Ets-1 gene polymorphisms with pediatric uveitis in a Han Chinese population., Methodology/principal Findings: A total of 520 patients and 1204 healthy controls were included in the present study. Five single-nucleotide polymorphisms (SNPs), miR-146a/rs2910164, miR-146a/rs57095329, miR-146a/rs6864584, ets-1/rs1128334 and ets-1/rs10893872 were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. The expression of Ets-1 in peripheral blood mononuclear cells from genotyped healthy controls was tested by real-time PCR. Two SNPs (rs2910164 and rs10893872) were associated with pediatric uveitis in this study. The frequencies of the rs2910164 GG genotype and G allele were significantly increased (Pc = 3.11×10(-4); Pc = 2.75×10(-6)) while the CC genotype and C allele were significantly decreased (Pc = 0.001; Pc = 2.75×10(-6)) in patients compared with normal controls. The frequencies of the rs10893872 CC genotype and C allele were significantly increased (Pc = 3.89×10(-4); Pc = 0.01) while the CT genotype and T allele were significantly decreased (Pc = 0.004; Pc = 0.01) in patients compared with normal controls. The SNP rs2910164 GG genotype and G/C allele were also associated with the presence of microvascular leakage as detected by fundus fluorescein angiography in pediatric uveitis (Pc = 0.01; Pc = 0.005, respectively). Ets-1 expression in rs10893872 CC carriers was significantly higher than in CT and TT individuals (Pc = 0.013). There was no association of the other three SNPs with pediatric uveitis., Conclusions: This study shows that miR-146a and Ets-1 are both associated with pediatric uveitis in Han Chinese. SNP rs10893872 may affect the genetic predisposition to pediatric uveitis by modulating expression of Ets-1.

Purpose: MicroRNAs (miRNAs) have emerged as a class of gene expression regulators involved in immune regulation. In the present study, we investigated the role of miRNA in two uveitis entities: Behcet's disease (BD) and Vogt Koyanagi Harada syndrome (VKH)., Methods: The expression of five miRNAs was studied in PBMCs, DCs, and CD4(+) T cells from BD patients with active and inactive uveitis, VKH patients with active uveitis, and healthy controls using real-time PCR. MiR-155 mimics and inhibitor were transfected to DCs to evaluate the effect on DC maturation and cytokine production by these cells and CD4(+) T cells. Luciferase reporter assays and Western blotting were performed to identify the target gene of miR-155., Results: Only miR-155 expression was significantly decreased in PBMCs and DCs from BD patients with active uveitis and no differences were observed in the miRNA expression in cells from patients with VKH as compared with controls. Overexpression of miR-155 in DCs was shown to inhibit the production of IL-6 and IL-1β, and to promote the expression of IL-10 by these cells. MiR-155 transfected DCs significantly inhibited intracellular IL-17 expression in allogeneic CD4(+) T cells; however, it did not influence the expression of cell surface markers CD80, CD40, CD83, CD86, and HLA-DR. Luciferase reporter assays revealed that TAB2 was a target gene of miR-155, which was confirmed by Western blotting., Conclusions: The present results suggest that miR-155 expression is decreased in active BD but not in VKH patients. Downregulated miR-155 may be involved in BD pathogenesis by targeting TAB2.

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. Functional studies were performed in the peripheral blood mononuclear cells (PBMCs) of 45 healthy men and 16 active male BD patients. Genotyping was performed using the MassARRAY System. The mRNA expressions of IL1RL1, IL18R1, IL18RAP, and SLC9A4 were assayed by real-time PCR and secretion of cytokines was examined by ELISA. Significantly lower frequencies of the rs12987977 GG genotype/G allele (P c = 8.93 × 10–7, OR = 0.39; P c = 2.60 × 10–3, OR = 0.77, respectively), rs12999364 TT genotype/T allele (P c = 3.15 × 10–4, OR = 0.51; P c = 1.13 × 10–2, OR = 0.80, respectively), and rs4851569 AA genotype/A allele (P c = 3.29 × 10–4, OR = 0.52; P c = 9.72 × 10–3, OR = 0.80, respectively) were observed in BD patients compared with the controls. Functional experiments revealed a downregulation of IL1RL1, IL18R1, and SLC9A4 and a decreased secretion of IFN-γ in the anti-CD3/CD28 antibody-treated PBMCs as well as a decreased production of TNF-α in the lipopolysaccharide (LPS)-stimulated PBMCs in carriers of the protective homozygous rs12987977/GG genotype compared with the TT genotype. Our findings show that functional SNPs—rs12987977, rs12999364, and rs4851569—in the IL1RL1–IL18R1 region confer susceptibility to ocular BD in a Chinese Han population. And IL1RL1, IL18R1, and SLC9A4 may be the target genes of rs12987977. [ABSTRACT FROM AUTHOR]

Purpose: To measure changes in the choroidal vascularity index (CVI) in chronic Vogt-Koyanagi-Harada (VKH) disease during a recurrent anterior uveitis attack.Methods: Forty VKH patients and 40 normal controls were included in this study. Choroidal images were recorded before and during a recurrent anterior uveitis attack, as well as after appropriate treatment. CVI was measured by the binarization technique using ImageJ software (Bethesda, MD).Results: The CVI was 0.75 ± 0.09 in quiescent VKH patients, which was significantly higher compared to healthy controls (0.70 ± 0.05, p ＜ 0.0001). The CVI significantly decreased to 0.72 ± 0.09 when granulomatous anterior uveitis appeared in these patients. However, it returned to 0.75 ± 0.08 after uveitis resolved.Conclusions: A significant decrease of the CVI occurred during recurrent anterior uveitis in chronic VKH. CVI may provide a novel parameter to guide the treatment of VKH disease. [ABSTRACT FROM AUTHOR]