Pathogenic role and diagnostic utility of interferon-α in histiocytic necrotizing lymphadenitis

Clin Immunol. 2024 Sep:266:110324. doi: 10.1016/j.clim.2024.110324. Epub 2024 Jul 18.

Abstract

Purpose: Histiocytic necrotizing lymphadenitis (HNL) is an inflammatory disease of unknown etiology clinically characterized by painful lymphadenopathy. This study aimed to investigate the role of interferon (IFN)-α in the pathogenesis of HNL and the clinical significance of serum IFN-α levels for the diagnosis and monitoring of HNL disease activity.

Methods: This study enrolled 47 patients with HNL and 43 patients with other inflammatory diseases that require HNL differentiation including malignant lymphoma (ML), bacterial lymphadenitis, and Kawasaki disease. Expression of IFN-stimulated genes (ISGs) and MX1 in the lymph nodes was measured by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay was used to quantify serum cytokine levels. The results were compared with the clinical features and disease course of HNL.

Results: Patients with HNL had a significantly elevated ISG expression in the lymph nodes compared with those with ML. MX1 and CD123, a specific marker of plasmacytoid dendritic cells (pDCs), were colocalized. In patients with HNL, serum IFN-α levels were significantly elevated and positively correlated with disease activity. The serum IFN-α level cutoff value for differentiating HNL from other diseases was 11.5 pg/mL.

Conclusion: IFN-α overproduction from pDCs may play a critical role in HNL pathogenesis. The serum IFN-α level may be a valuable biomarker for the diagnosis and monitoring of disease activity in patients with HNL.

Keywords: Histiocytic necrotizing lymphadenitis; Interferon stimulated gene; Interferon-α; Kikuchi–Fujimoto disease; Plasmacytoid dendritic cell; Subacute necrotizing lymphadenitis.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Cytokines / blood
  • Cytokines / metabolism
  • Dendritic Cells* / immunology
  • Dendritic Cells* / metabolism
  • Female
  • Histiocytic Necrotizing Lymphadenitis* / blood
  • Histiocytic Necrotizing Lymphadenitis* / diagnosis
  • Histiocytic Necrotizing Lymphadenitis* / immunology
  • Humans
  • Interferon-alpha* / blood
  • Lymph Nodes* / pathology
  • Lymphoma / blood
  • Lymphoma / diagnosis
  • Lymphoma / immunology
  • Male
  • Middle Aged
  • Mucocutaneous Lymph Node Syndrome / blood
  • Mucocutaneous Lymph Node Syndrome / diagnosis
  • Mucocutaneous Lymph Node Syndrome / immunology
  • Myxovirus Resistance Proteins / blood
  • Myxovirus Resistance Proteins / genetics
  • Myxovirus Resistance Proteins / metabolism
  • Young Adult

Substances

  • Interferon-alpha
  • Myxovirus Resistance Proteins
  • MX1 protein, human
  • Biomarkers
  • Cytokines