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Castleman disease human lymph node tissue

ABSTRACT: Castleman disease human lymph node tissue

PROVIDER: PRJNA1096704 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28573400_1.fastq.gz	Fastqsanger.gz
	SRR28573400_2.fastq.gz	Fastqsanger.gz
	SRR28573401_1.fastq.gz	Fastqsanger.gz
	SRR28573401_2.fastq.gz	Fastqsanger.gz
	SRR28573402_1.fastq.gz	Fastqsanger.gz

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Castleman disease human lymph node tissue

Project description:Castleman disease (CD) is a rare hematologic disorder involving inflamed lymph nodes and distinct histological features. Unicentric Castleman disease (UCD) and idiopathic multicentric Castleman disease (iMCD) are of particular interest as their etiologies are poorly understood and treatment options are limited. As iMCD patients, and occasionally UCD patients, also present with a cytokine storm, we sought to investigate if the cytokine release from iMCD and UCD subtypes have pathogenic origins as observed in human herpesvirus 8 MCD (HHV-8-MCD). To identify potential active viruses that may be contributing to immune system dysregulation in Castleman Disease tissues we conducted bulk RNA sequencing on FFPE preserved lymph node tissue from patients with various phenotypes including Idiopathic multicentric Castleman disease (n = 9), systemic lupus erythematosus (n =3), diffuse large B cell lymphoma (n =5), and reactive lymph nodes with inconclusive pathology (n = 7).

2025-01-15 | GSE263321 | GEO

The lymph node transcriptome of unicentric and idiopathic multicentric Castleman disease

Project description:Castleman disease is polyclonal lymphoproliferative disorder characterized by unicentric or multicentric lymphadenopathy with characteristic histomorphologic features, in addition to variable inflammatory symptomatology. The molecular mechanisms and etiologies of unicentric Castleman disease (UCD) and idiopathic multicentric Castleman disease (iMCD) are poorly understood, and identification of targetable disease mediators remains an unmet clinical need. We performed whole exome sequencing on lymph node biopsies from patients with UCD and iMCD; and compared the transcriptomic profile to that of benign control lymph nodes. We identified significantly upregulated genes in UCD (443), iMCD (316) or both disease subtypes (51); in addition to downregulated genes in UCD (321), iMCD (105) or both (10). The transcriptomes of UCD and iMCD showed enrichment and upregulation of elements of the complement cascade. By immunohistochemistry, C4d deposits indicative of complement activation were present in UCD and iMCD mostly within abnormally regressed germinal centers, but also in association with plasma cell clusters, endothelial cells and stroma cells proliferations. Other enriched gene sets included collagen organization, S1P3 pathway and VEGFR pathway in UCD; and humoral response, oxidative phosphorylation and proteosome in iMCD. Analysis of cytokine transcripts showed upregulation of CXCL13 but not IL-6 in UCD and iMCD. Among angiogenic mediators, the VEGFR1 ligand placental growth factor (PGF) was upregulated in both disease subtypes. We hereby report for the first time the whole lymph node transcriptome of UCD and iMCD, underscoring findings that could aid in the discovery of targetable disease mediators.

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Project description:The lymph node transcriptome of unicentric and idiopathic multicentric Castleman disease

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Project description:Idiopathic Multicentric Castleman Disease (iMCD) is a rare IL-6-driven hematological disorder characterized by systemic lymphadenopathy, elevated immunoglobulin levels, and prominent plasmacytosis in the bone marrow and lymph nodes. Here, we present an unusual occurrence of iMCD in identical twins. Using single cell sequencing, we identified nodal endothelial cells and fibroblastic reticular cells as the source of IL-6 signals. An “inflammatory” peripheral monocytosis enriched for the expression of S100A family genes was evident in both twins, as well as a group of monocytes expressing cytotoxic gene signatures in the affected twin with milder clinical manifestations.

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Common Connective Tissue Disorder and Anti-Cytokine Autoantibodies are Enriched in Idiopathic Multicentric Castleman Disease Patients

Project description:We measued IgG autoantibodies associated with Connective Tissue Diseases (CTDs) and Anti-Cytokine Antibodies (ACA) in idiopathic Multicentric Castleman Disease (iMCD) patients and healthy controls who received the BNT162b2 vaccine.

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