Single-cell landscape of idiopathic multicentric Castleman disease in identical twins.
Blood
; 143(18): 1837-1844, 2024 May 02.
Article
em En
| MEDLINE
| ID: mdl-38170173
ABSTRACT
ABSTRACT Idiopathic multicentric Castleman disease (iMCD) is a rare cytokine-driven disorder characterized by systemic inflammation, generalized lymphadenopathy, and organ dysfunction. Here, we present an unusual occurrence of iMCD in identical twins and examined the immune milieu within the affected lymphoid organs and the host circulation using multiomic high-dimensional profiling. Using spatial enhanced resolution omics sequencing (Stereo-seq) transcriptomic profiling, we performed unsupervised spatially constrained clustering to identify different anatomic structures, mapping the follicles and interfollicular regions. After a cell segmentation approach, interleukin 6 (IL-6) pathway genes significantly colocalized with endothelial cells and fibroblastic reticular cells, confirming observations using a single-cell sequencing approach (10× Chromium). Furthermore, single-cell sequencing of peripheral blood mononuclear cells revealed an "inflammatory" peripheral monocytosis enriched for the expression of S100A family genes in both twins. In summary, we provided evidence of the putative cell-of-origin of IL-6 signals in iMCD and described a distinct monocytic host immune response phenotype through a unique identical twin model.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Gêmeos Monozigóticos
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Hiperplasia do Linfonodo Gigante
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Interleucina-6
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Análise de Célula Única
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Singapura