Kikuchi-Fujimoto disease is mediated by an aberrant type I interferon response.
Elizabeth Y LiJason XuNya D NelsonDavid T TeacheyKai TanNeil RombergEd BehrensVinodh PillaiPublished in: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (2021)
Kikuchi-Fujimoto disease (KFD) is a reactive lymphadenitis of unclear etiology. To understand the pathogenesis of KFD, we performed targeted RNA sequencing of a well-characterized cohort of 15 KFD specimens with 9 non-KFD lymphadenitis controls. Two thousand and three autoimmunity-related genes were evaluated from archived formalin-fixed paraffin-embedded lymph node tissue and analyzed by a bioinformatics approach. Differential expression analysis of KFD cases compared to controls revealed 44 significantly upregulated genes in KFD. Sixty-eight percent of these genes were associated with the type I interferon (IFN) response pathway. Key component of the pathway including nucleic acid sensors, IFN regulatory factors, IFN-induced antiviral proteins, IFN transcription factors, IFN-stimulated genes, and IFN-induced cytokines were significantly upregulated. Unbiased gene expression pathway analysis revealed enrichment of IFN signaling and antiviral pathways in KFD. Protein-protein interaction analysis and a molecular complex detection algorithm identified a densely interacting 15-gene module of type I IFN pathway genes. Apoptosis regulator IFI6 was identified as a key seed gene. Transcription factor target analysis identified enrichment of IFN-response elements and IFN-response factors. T-cell-associated genes were upregulated while myeloid and B-cell-associated genes were downregulated in KFD. CD123+ plasmacytoid dendritic cells (PDCs) and activated T cells were noted in KFD. In conclusion, KFD is mediated by an aberrant type I interferon response that is likely driven by PDCs and T cells.
Keyphrases
- dendritic cells
- transcription factor
- genome wide identification
- immune response
- genome wide
- regulatory t cells
- gene expression
- lymph node
- dna methylation
- genome wide analysis
- bioinformatics analysis
- squamous cell carcinoma
- nucleic acid
- protein protein
- single cell
- diabetic rats
- machine learning
- high glucose
- radiation therapy
- cell proliferation
- endothelial cells
- deep learning
- signaling pathway
- locally advanced
- rectal cancer
- low cost