Impaired expression of innate immunity-related genes in IgG4-related disease: A possible mechanism in the pathogenesis of IgG4-RD

Mod Rheumatol. 2020 May;30(3):551-557. doi: 10.1080/14397595.2019.1621475. Epub 2019 Jul 11.

Abstract

Background: IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. The pathogenesis of this disease is not clear. Transcriptome analysis was performed to identify genes over- and under-expressed in patients with IgG4-RD.Method: DNA microarray analysis was performed using RNA from peripheral blood mononuclear cells of two patients with IgG4-RD and four healthy individuals. Genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy were identified. Four genes related to innate immunity such as transcobalamin I (TCN1), secretory leukocyte peptidase inhibitor (SLPI), bactericidal/permeability-increasing protein (BPI) and lactotransferrin (LTF) were assessed by real-time PCR in 15 IgG4-RD patients and 13 healthy individuals.Result: DNA microarray analysis identified 30 genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy. Real-time RT-PCR showed that the levels of mRNAs encoding TCNI and SLPI, except for BPI and LTF, were significantly lower in patients with IgG4-RD than in healthy people. The levels of all four mRNAs in patients with IgG4-RD were significantly increased after steroid treatment.Conclusion: These results indicate that reduction in expression of innate immunity-related genes may participate in the pathogenesis of IgG4-RD that steroid treatment may rectify impaired innate immunity as well as acquired immunity.

Keywords: DNA microarray analysis; IgG4-related disease; acquired immunity; innate immunity; innate immunity related gene.

MeSH terms

  • Adult
  • Female
  • Humans
  • Immunity, Innate / genetics*
  • Immunoglobulin G4-Related Disease / genetics*
  • Immunoglobulin G4-Related Disease / metabolism
  • Lactoferrin / genetics
  • Lactoferrin / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Secretory Leukocyte Peptidase Inhibitor / genetics
  • Secretory Leukocyte Peptidase Inhibitor / metabolism
  • Transcobalamins / genetics
  • Transcobalamins / metabolism
  • Transcriptome*

Substances

  • LTF protein, human
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • Transcobalamins
  • Lactoferrin