Dataset Information

Altered gut microbiome composition in patients with Vogt-Koyanagi-Harada disease.

ABSTRACT:

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.

SUBMITTER: Ye Z

PROVIDER: S-EPMC7524263 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder affecting multiple organs, including eyes, skin, and central nervous system. It is known that monocytes significantly contribute to the development of autoimmune disease. However, the subset heterogeneity with unique functions and signatures in human circulating monocytes and the identity of disease-specific monocytic populations remain largely unknown. Here, we employed an advanced single-cell RNA sequencing technology to systematically analyze 11259 human circulating monocytes and genetically defined their subpopulations. We constructed a precise atlas of human blood monocytes，identified 6 subpopulations: including S100A12-; HLA-; CD16-; proinflammatory-; megakaryocyte-like-; and NK-like-monocytes subsets, and uncovered 2 previously unidentified subsets: HLA- and megakaryocyte-like monocyte subsets. Relative to healthy individuals, cellular composition, gene expression signatures, and activation states were markedly alternated in VKH patients utilizing cell type-specific programs, especially the CD16- and proinflammatory monocyte subpopulation. Notably, we discovered a disease-relevant subgroup, proinflammatory monocytes, which showed a discriminative gene expression signature indicative of inflammation, antiviral activity, and pathologic activation, and converted into pathologic activation state implicating the active inflammation during VKH disease. Additionally, we found the cell type-specific transcriptional signature of proinflammatory monocytes, ISG15, which could act as a disease biomarker to more accurately reflect disease activity and treatment response than symptom evaluation. Taken together, in this landmark study we present novel discoveries on accurate classification, molecular markers, and signaling pathways for VKH disease-associated monocytes and therapeutically targeting this proinflammatory monocyte subpopulation would provide an attractive approach for treating VKH as well as other autoimmune diseases.