Single-cell landscape of idiopathic multicentric Castleman disease in identical twins

Idiopathic multicentric Castleman disease (iMCD) is a rare cytokine-driven disorder characterized by systemic in fl ammation, 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 pro fi ling. Using spatial enhanced resolution omics sequencing (Stereo-seq) transcriptomic pro fi ling, 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 signi fi cantly colocalized with endothelial cells and fi broblastic reticular cells, con fi rming observations using a single-cell sequencing approach (10x Chromium). Furthermore, single-cell sequencing of peripheral blood mononuclear cells revealed an "in fl ammatory" 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 twin model.