Risk factors, clinical features and treatment of Behçet's disease uveitis

Zhong, Zhenyu; Su, Guannan; Yang, Peizeng

doi:10.1016/j.preteyeres.2023.101216

Cited by 11 publications

(7 citation statements)

References 249 publications

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“…Traditional therapeutic approaches (using local and systemic immunomodulatory and immunosuppressive drugs) for treating auto-inflammatory disease have limited efficacy and serious side effects 52 . Emerging investigations reported IFN-α2a offering moderate benefits for treating auto-inflammatory Behçet’s disease, especially severe and relapsing uveitis 53 , 54 . Several clinical trials discovered that the outcomes and efficacy of IFN-α2a for BU are circumstantial and, in most cases, sex-specific 55 .…”

Section: Resultsmentioning

confidence: 99%

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

Wang,

Ma,

Gong

et al. 2024

Cell Discov

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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. Using a combination of single-cell RNA sequencing analysis, neutrophil-specific genetic knockouts and transfer experiments, we discovered dysregulation of two unconventional (interferon-α responsive and T cell regulatory) neutrophil subsets leading to male-biased incidence, severity and poor prognosis of auto-inflammatory Behçet’s uveitis. Genome-wide association study (GWAS) and exosome study revealed that male-specific negative effects of both genetic factors and circulating exosomes on unconventional neutrophil subsets contributed to male-specific vulnerability to disease. Collectively, our findings identify sex-specifically distinct neutrophil subsets and highlight unconventional neutrophil subsets as sex-specific therapeutic targets to limit inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

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

Wang,

Ma,

Gong

et al. 2024

Cell Discov

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“…Current mainstay therapies for AU bring unsatisfactory clinical benefits and are accompanied by a series of side effects leading to poor patient compliance. 26 , 27 Thus, the pathogenesis of AU needs further investigation to provide new potential targets. Extensive research has demonstrated full‐blown disease developing by D14‐21 after IRBP immunization utilizing the EAU model that is widely used for human endogenous posterior uveitis.…”

Section: Discussionmentioning

confidence: 99%

Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis

Liu,

Liao,

et al. 2024

MedComm

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Autoimmune uveitis (AU) is a kind of immune‐mediated disease resulting in irreversible ocular damage and even permanent vision loss. However, the precise mechanism underlying dynamic immune changes contributing to disease initiation and progression of AU remains unclear. Here, we induced an experimental AU (EAU) model with IRBP651‐670 and found that day[D]14 was the inflammatory summit with remarking clinical and histopathological manifestations and the activation of retinal microglia exhibited a time‐dependent pattern in the EAU course. We conducted single‐cell RNA sequencing of retinal immune cells in EAU mice at four time points and found microglia constituting the largest proportion, especially on D14. A novel inflammatory subtype (Cd74high Ccl5high) of retinal microglia was identified at the disease peak that was closely associated with modulating immune responses. In vitro experiments indicated that inflammatory stimuli induced proinflammatory microglia with the upregulation of CD74 and CCL5, and CD74 overexpression in microglia elicited their proinflammatory phenotype via nuclear factor‐kappa B signaling that could be attenuated by the treatment of neutralizing CCL5 antibody to a certain extent. In‐vivo blockade of Cd74 and Ccl5 effectively alleviated retinal microglial activation and disease phenotype of EAU. Therefore, we propose targeting CD74 and CCL5 of retinal microglia as promising strategies for AU treatment.

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“…Finally, since there are many inflammatory factors involved in VKH disease that have an impact and this study only focused on the most significant ones, such as TNF‐α, IL‐6. [ 29 , 48 , 49 ] Therefore, further studies are needed to elucidate the roles of these variants in VKH disease and other uveitis entities in other ethnic populations.…”

Section: Discussionmentioning

confidence: 99%

“…Although exons (protein‐coding regions) account for only 1% of the human genome, 85% of disease‐causing mutations in the human genome are in exonic regions. [ 19 , 29 ] Therefore, we performed a whole‐exome sequencing (WES) study to complement the genome‐wide association study (GWAS) by examining the direct relationship between 2573 controls and 229 VKH patients of Han Chinese descent. We identified that a variant in the olfactory receptor 11H1 (OR11H1) gene was significantly associated with VKH disease.…”

Section: Introductionmentioning

confidence: 99%

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

Li,

Wang,

Wang

et al. 2024

Advanced Science

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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.188T>C (p Val63Ala) variant in the olfactory receptor 11H1 (OR11H1) gene is found to be significantly associated with VKH disease (rs71235604, Pcombined = 7.83 × 10−30, odds ratio = 3.12). Functional study showes that OR11H1‐A63 significantly increased inflammatory factors production and exacerbated barrier function damage. Further studies using RNA‐sequencing find that OR11H1‐A63 markedly increased growth arrest and DNA‐damage‐inducible gamma (GADD45G) expression. Moreover, OR11H1‐A63 activates the MAPK and NF‐κB pathways, and accelerates inflammatory cascades. In addition, inhibiting GADD45G alleviates inflammatory factor secretion, likely due to the regulatory effect of GADD45G on the MAPK and NF‐κB pathways. Collectively, this study suggests that the OR11H1‐A63 missense mutation may increase susceptibility to VKH disease in a GADD45G‐dependent manner.

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Risk factors, clinical features and treatment of Behçet's disease uveitis

Cited by 11 publications

References 249 publications

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

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

Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis

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

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