Stage classification of IgG4-related dacryoadenitis and sialadenitis by the serum cytokine environment

Mod Rheumatol. 2018 Nov;28(6):1004-1008. doi: 10.1080/14397595.2018.1436029. Epub 2018 Feb 23.


Objectives: Patients with immunoglobulin-G4 related disease (IgG4-RD) diagnosed according to the comprehensive diagnostic criteria (CDC) show varied therapeutic responses and prognoses. We assumed that there are clinical stages in IgG4-RD and have verified it using serum cytokine levels in the groups classified by lesion distribution.

Methods: Definite IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) cases were divided according to the CDC for IgG4-RD into 11 cases with focal type and 30 cases with systemic type. The levels of serum interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, IL-15, IL-21, interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and monocyte chemotactic protein (MCP)-1 were measured in healthy controls, allergic patients, probable IgG4-RD cases, and focal and systemic type cases. The cytokine environment was analyzed in each group. The 52 definite IgG4-RD cases were next classified into four groups with cluster analysis in terms of therapeutic responses and prognosis. The relationships between each cytokine level and therapeutic responses were also analyzed.

Results: Both serum IL-5 and IFN-α concentrations were very low in healthy controls, but they increased in the allergic cases, probable cases, and focal and systemic type cases. The level of serum IL-5 was significantly higher in definite cases than in healthy controls. The serum IL-5 level was also significantly increased in the groups with a poor prognosis than in the good prognosis group.

Conclusion: These results suggest that there are clinical stages in IgG4-RD, and serum IL-5 play roles in the pathogenesis of IgG4-RD.

Keywords: IgG4-related disease; interferon-α; interleukin-5; staging classification.

MeSH terms

  • Aged
  • Dacryocystitis* / blood
  • Dacryocystitis* / classification
  • Dacryocystitis* / diagnosis
  • Dacryocystitis* / immunology
  • Female
  • Humans
  • Immunoglobulin G / blood*
  • Immunologic Tests / methods
  • Inflammation / immunology
  • Interferon-alpha / blood*
  • Interleukin-5 / blood*
  • Male
  • Middle Aged
  • Patient Acuity
  • Patient Care Management / methods
  • Prognosis
  • Salivary Glands / immunology
  • Sialadenitis* / blood
  • Sialadenitis* / diagnosis
  • Sialadenitis* / immunology
  • Sialadenitis* / therapy
  • Tumor Necrosis Factor-alpha / blood


  • Immunoglobulin G
  • Interferon-alpha
  • Interleukin-5
  • Tumor Necrosis Factor-alpha