title: Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease.
abstract: OBJECTIVE
  Mikulicz disease has been considered to be a subtype of Sjögren's syndrome (SS). However, recent studies have suggested that Mikulicz disease is an IgG4-related disease and is distinguishable from SS. In addition, it has been reported that both interleukin-4 (IL-4) and IL-10 induce IgG4 production and inhibit IgE. This study was undertaken to examine the expression of these cytokines in patients with Mikulicz disease and patients with SS.
  
  
  METHODS
  Labial salivary gland (LSG) sections from 15 patients with Mikulicz disease and 18 patients with SS were examined for subsets of the infiltrating lymphocytes, expression patterns of messenger RNA (mRNA) for cytokines/chemokines, and relationships between the IgG4:IgG ratio and the expression of mRNA for IL-4 or IL-10.
  
  
  RESULTS
  Immunohistochemical analysis showed lymphocyte infiltration of various subsets in the LSGs of SS patients, and the selective infiltration of IgG4-positive plasma cells and Treg cells in the LSGs of Mikulicz disease patients. The levels of mRNA for both Th1 and Th2 cytokines and chemokines in LSGs from patients with SS were significantly higher than in controls, while the expression of both Th2 and Treg cells was significantly higher in the patients with Mikulicz disease than in controls. Furthermore, the expression of IL-4 or IL-10 in the LSGs was correlated with the IgG4:IgG ratio.
  
  
  CONCLUSIONS
  These results suggest that the pathogenesis of Mikulicz disease is different from that of SS. Mikulicz disease is a unique inflammatory disorder characterized by Th2 and regulatory immune reactions that might play key roles in IgG4 production.
authors: Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors: Akihiko
authors: A
authors: Tanaka
authors: Masafumi
authors: M
authors: Moriyama
authors: Hitoshi
authors: H
authors: Nakashima
authors: Katsuhisa
authors: K
authors: Miyake
authors: Jun-Nosuke
authors: JN
authors: Hayashida
authors: Takashi
authors: T
authors: Maehara
authors: Shouichi
authors: S
authors: Shinozaki
authors: Yoshiaki
authors: Y
authors: Kubo
authors: Seiji
authors: S
authors: Nakamura
mesh_terms: D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics; D007155:Immunologic Factors / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008882:Mikulicz' Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D012470:Salivary Glands, Minor / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D018925:Chemokines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D012333:RNA, Messenger; D019707:Receptors, Chemokine