Journal Article

Kikuchi-Fujimoto disease is mediated by an aberrant type I interferon response

Tan, Kai, Li, Elizabeth Y., Teachey, David T., Romberg, Neil, Behrens, Ed, Xu, Jason, Nelson, Nya D., Pillai, Vinodh

2022

Overview

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.

• Publisher: Nature Publishing Group US,Elsevier Limited
• Subject: 13/51 / 38/39 / 38/91 / 631/208/199 / 692/699/1541 / Antiviral Agents / Antiviral drugs / Apoptosis / Autoimmunity / Bioinformatics / CD123 antigen / Dendritic cells / Etiology / Gene expression / Histiocytic Necrotizing Lymphadenitis - diagnosis / Histiocytic Necrotizing Lymphadenitis - genetics / Histiocytic Necrotizing Lymphadenitis - pathology / Humans / Interferon / Interferon Type I - genetics / Laboratory Medicine / Lymph nodes / Lymph Nodes - pathology / Lymphadenitis / Lymphadenitis - pathology / Lymphatic diseases / Lymphocytes B / Lymphocytes T / Medicine / Medicine & Public Health / Paraffin / Pathology / Regulatory sequences / Transcription factors