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.

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. Fundus fluorescein angiography was used to assess the presence of retinal vasculitis. Results: A total of 1,867 patients with pediatric uveitis were seen between December 2008 and January 2018, of whom 1,364 had undergone fundus fluorescein angiography examination. Idiopathic uveitis was the most common entity, accounting for 81.2%. Among these patients with idiopathic uveitis, 79.6% had retinal vasculitis in at least one eye. After 1-year treatment with oral prednisone mostly combined with cyclosporine, 76.3% patients in the retinal vasculitis group achieved control of their ocular inflammation, which was significantly lower as compared with 85.1% in those without (P = 0.008). Retinal vasculitis was an independent predictor for a lower probability of inflammation control after 1-year treatment. Visual function (best-corrected visual acuity > 20/25 in the better seeing eye) was worse in the retinal vasculitis group than in the control group after 5 years. Conclusion: Almost 80% of patients with pediatric idiopathic uveitis show manifestations of retinal vasculitis, which is associated with a lower probability of inflammation control resulting in a worse visual prognosis.

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AimsTo investigate the effect of succinic acid on the development of experimental autoimmune uveitis (EAU) and the underlying mechanism.MethodsSuccinic acid was administrated intraperitoneally to evaluate its effects on immune response and EAU in mice. Intraocular inflammation was evaluated by histopathological scoring. Frequencies of Th1/Th17 cells were measured by flow cytometry. Concentrations of IFN-γ/IL-17A, neutrophil elastase (NE) and myeloperoxidase (MPO) were determined by enzyme-linked immunosorbent test. Infiltration of neutrophils and generation of neutrophil extracellular traps (NETs) within the eye were assessed by immumofluorescence. NETs formation in extracellular matrix was visualised by laser scanning confocal microscopy. Succinate receptor (SUCNR1) antagonist was used to investigate its effect on the generation of NETs.ResultsIntraperitoneal injection of succinic acid exacerbated EAU severity as evidenced by severe histological changes in association with elevated frequencies of splenic Th1/Th17 cells, and upregulated levels of IFN-γ/IL-17A and NETs in plasma. In vitro experiments showed that succinic acid could promote the generation of NETs by neutrophils as shown by increased expression of NE and MPO.NETs could increase the frequencies of Th1/Th17 cells in CD4+ T cells and their expression of IFN-γ/IL-17A. In the experiment of receptor antagonism, the upregulatory effect of succinic acid on NETs could be significantly blocked by SUCNR1 antagonist.ConclusionsSuccinic acid could worsen EAU induced by IRBP in mice. This effect was possibly mediated by its upregulation on NETs generation and frequencies of Th1/Th17 cells in affiliation with increased production of IFN-γ/IL-17A through succinic acid-SUCNR1 axis.