ABSTRACT
Purpose: To determine the possible microbiome related to Vogt-Koyanagi-Harada (VKH) disease in comparison to patients with noninfectious anterior scleritis and healthy people. Methods: Fecal samples were extracted from 42 individuals, including 11 patients with active VKH, 11 healthy people, and 20 patients with noninfectious anterior scleritis. We amplified the V3 to V4 16S ribosomal DNA (rDNA) region to obtain the target sequence. Then, the target sequence was amplified by polymerase chain reaction. The obtained target sequences were sequenced by high-throughput 16S rDNA analysis. Results: At the genus level, there were three enriched (Stomatobaculum, Pseudomonas, Lachnoanaerobaculum) and two depleted (Gordonibacter, Slackia) microbes that were detected only in patients with VKH. There were 10 enriched and 12 depleted microbes that were observed in both patients with VKH disease and noninfectious anterior scleritis (P < 0.05). The interactions of these microbes were graphed. Tyzzerella and Eggerthella were the nodes of interaction between these microorganisms, which were regulated by both positive and negative aspects, but the expression level in patients with active VKH was upregulated. Conclusions: Special or nonspecial enrichment and decreased intestinal microbes were observed in patients with active VKH. The action mechanism of these microbes needs further study.
Subject(s)
Actinobacteria/physiology , Clostridiales/physiology , Gastrointestinal Microbiome/physiology , Pseudomonas/physiology , Uveomeningoencephalitic Syndrome/microbiology , Adult , Case-Control Studies , DNA, Bacterial/genetics , Dysbiosis/microbiology , Feces/microbiology , Female , Genotyping Techniques , Healthy Volunteers , Humans , Male , Middle Aged , RNA, Ribosomal, 16S/genetics , Scleritis/microbiologyABSTRACT
Vogt-Koyanagi-Harada (VKH) syndrome is an autoimmune disorder characterized often by acute diffuse uveitis, also known as idiopathic uveoencephalitis. The associated complications can potentially affect multiple systems throughout the body, including eyes, ears, skin and nervous system. Although the pathogenesis of VKH syndrome remains unclear, it has been established that the various genetic factors, epigenetic factors and the imbalance in immune regulation can significantly contribute to the development of this disease. In addition, the experimental autoimmune uveitis (EAU) has been commonly used to further explore the pathogenesis of the disease. Herein, in this review article, we discuss about the major research advances made in understanding of the different epigenetic factors and gut microbes involved in the pathogenesis of VKH syndrome as well as EAU. The information discussed can help to better understand the pathogenesis of VKH syndrome, and thereby might provide a basis for finding novel molecular targets and innovative treatment strategies in the future.
Subject(s)
Epigenesis, Genetic , Gastrointestinal Microbiome/genetics , Uveomeningoencephalitic Syndrome/genetics , Uveomeningoencephalitic Syndrome/microbiology , DNA Methylation/genetics , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Uveomeningoencephalitic Syndrome/pathologyABSTRACT
BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder characterized by granulomatous panuveitis. Gut microbiome has been considered to play a role in the pathogenesis of this disease but whether the alternation of gut microbiome was involved is unclear. This study was set up to identify abnormalities of gut microbiome composition in VKH disease. RESULTS: Depleted butyrate-producing bacteria, lactate-producing bacteria and methanogens as well as enriched Gram-negative bacteria were identified in the active VKH patients, as well as in VKH patients of Mix enterotype and Bacteroides enterotype. Changes of gut microbiome in the VKH patients were partially restored after an immunosuppressive treatment. The disease susceptibility genotype HLA-DRA was associated with Bacteroides sp.2.1.33B, Paraprevotella clara, Alistipes finegoldii and Eubacterium eligens. A microbial marker profile including 40 disease-associated species was established to differentiate patients from controls. Another microbial marker profile including 37 species was found to be associated with the response to treatment. An animal experiment showed that transfer of gut microbiome from VKH patients could significantly exacerbate disease activity clinically and pathologically in the recipient mice. CONCLUSION: Our results revealed a distinct gut microbiome signature in VKH patients and showed an exacerbating effect of this gut microbiome on experimental autoimmune uveitis (EAU). We also developed two microbial marker profiles in differentiating VKH patients from healthy controls as well as predicting the effectiveness of treatment.
Subject(s)
Dysbiosis/microbiology , Gastrointestinal Microbiome , Uveomeningoencephalitic Syndrome/microbiology , Adrenal Cortex Hormones/therapeutic use , Adult , Animals , Biodiversity , Butyrates/metabolism , DNA, Bacterial , Disease Models, Animal , Fecal Microbiota Transplantation , Feces/microbiology , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotyping Techniques , Humans , Immunosuppressive Agents/therapeutic use , Lactic Acid/metabolism , Male , Mice , Prognosis , Whole Genome SequencingSubject(s)
Brucellosis/diagnosis , Choroiditis/diagnosis , Eye Infections, Bacterial/diagnosis , Retinal Detachment/diagnosis , Uveomeningoencephalitic Syndrome/diagnosis , Anti-Bacterial Agents/therapeutic use , Brucella/isolation & purification , Brucellosis/drug therapy , Brucellosis/microbiology , Choroiditis/drug therapy , Choroiditis/microbiology , Dexamethasone/therapeutic use , Doxycycline/therapeutic use , Drug Therapy, Combination , Eye Infections, Bacterial/drug therapy , Eye Infections, Bacterial/microbiology , Fluorescein Angiography , Glucocorticoids/therapeutic use , Humans , Prednisone/therapeutic use , Retinal Detachment/drug therapy , Retinal Detachment/microbiology , Streptomycin/therapeutic use , Uveomeningoencephalitic Syndrome/drug therapy , Uveomeningoencephalitic Syndrome/microbiologyABSTRACT
AIMS: To determine the levels of IgG class antibodies to recombinant heat shock protein 60 kDa of Yersinia enterocolitica (rHSP60Ye), Klebsiella pneumoniae (rHSP60Kp), Escherichia coli (rHSP60Ec), Shigella flexneri (rHSP60Sf), and Streptococcus pyogenes (rHSP60Sp) in the serum of patients with HLA-B27 associated acute anterior uveitis (HLA-B27 associated AAU), idiopathic acute anterior uveitis (idiopathic AAU), pars planitis, Vogt-Koyanagi-Harada (VKH), and healthy subjects. METHODS: The genes that code for HSP60Ye, HSP60Kp, HSP60Ec, HSP60Sf, and HSP60Sp were cloned by PCR from genomic DNA. The rHSPs were purified by affinity using a Ni-NTA resin. The serum levels of IgG class antibodies to rHSP60s were determined by ELISA in patients with uveitis (n = 42) and in healthy subjects (n = 25). RESULTS: The majority of patients with uveitis had higher levels of IgG class antibodies to rHSP60Ye compared with levels of healthy subjects (p = 0.01), although these differences were only observed in the HLA-B27 associated AAU (p = 0.005) and in pars planitis patients (p = 0.001). The levels of IgG antibodies to the rHSP60Kp, rHSP60Sf, rHSP60Ec, and rHSP60Sp were similar in patients with uveitis and in healthy subjects (p>0.05). CONCLUSION: The results suggest that HSP60Ye could be involved in the aetiology of HLA-B27 associated AAU and pars planitis.
Subject(s)
Antibodies, Bacterial/blood , Chaperonin 60/immunology , Immunoglobulin G/blood , Pars Planitis/microbiology , Uveitis, Anterior/microbiology , Yersinia enterocolitica/immunology , Acute Disease , Adolescent , Adult , Female , Genetic Predisposition to Disease , HLA-B27 Antigen/blood , Humans , Male , Middle Aged , Odds Ratio , Pars Planitis/immunology , Recombinant Proteins/immunology , Recurrence , Uveitis, Anterior/immunology , Uveomeningoencephalitic Syndrome/immunology , Uveomeningoencephalitic Syndrome/microbiologyABSTRACT
Research was carried out on isolating and identification of a virus in the cerebrospinal fluid of a patient with the Vogt-Koyanagi syndrome (uveomeningeal encephalitis). Results were negative. It was not possible to detect any virus causing the disease in this case. This research was the first such study carried out in Brazil.
