title: Analysis of IgG4 class switch-related molecules in IgG4-related disease.
abstract: BACKGROUND
  Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a new disease entity characterized by high serum IgG4 levels, IgG4-positive plasmacytic infiltration, and fibrosis in various organs. The purpose of this study was to determine the mechanism of upregulation of IgG4 class switch recombination in IgG4-RD.
  
  
  METHODS
  We extracted RNA from peripheral blood mononuclear cells (PBMCs) of patients with IgG4-RD (n = 6), Sjögren syndrome (SS) (n = 6), and healthy controls (n = 8), from CD3-positive T cells and CD20-positive B cells sorted from PBMCs of patients with IgG4-RD (n = 3), SS (n = 4), and healthy controls (n = 4), as well as from labial salivary glands (LSGs) of patients with IgG4-RD (n = 11), SS (n = 13), and healthy controls (n = 3). The mRNA expression levels of IgG4-specific class switch-related molecules, such as Th2 cytokines (IL-4 and IL-13), Treg cytokines (IL-10 and TGF-β), and transcriptional factors (GATA3 and Foxp3) were examined with quantitative polymerase chain reaction (PCR). IgG4-nonspecific class switch-related molecules, such as CD40, CD154, BAFF, APRIL, IRF4, and AID, were also examined.
  
  
  RESULTS
  The expression levels of Treg cytokines (IL-10 and TGF-β) and AID were significantly higher in LSGs of IgG4-RD than in SS and the controls (P < 0.05, each). In contrast, those of CD40 and CD154 were significantly lower in PBMCs of IgG4-RD than in SS (P < 0.05, each), whereas CD40 in CD20-positive B cells and CD154 in CD3-positive T cells were comparable in the three groups.
  
  
  CONCLUSIONS
  Overexpression of IL-10, TGF-β, and AID in LSGs might play important roles in the pathogenesis of IgG4-RD, such as IgG4-specific class-switch recombination and fibrosis. IgG4 class-switch recombination seems to be mainly upregulated in affected organs.
authors: Hiroto
authors: H
authors: Tsuboi
authors: Naomi
authors: N
authors: Matsuo
authors: Mana
authors: M
authors: Iizuka
authors: Sayaka
authors: S
authors: Tsuzuki
authors: Yuya
authors: Y
authors: Kondo
authors: Akihiko
authors: A
authors: Tanaka
authors: Masafumi
authors: M
authors: Moriyama
authors: Isao
authors: I
authors: Matsumoto
authors: Seiji
authors: S
authors: Nakamura
authors: Takayuki
authors: T
authors: Sumida
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000097:blood* / Q000175:diagnosis; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G