Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease

Akihiko Tanaka, Masafumi Moriyama, Hitoshi Nakashima, Katsuhisa Miyake, Hayashida Jun-Nosuke, takashi maehara, Shouichi Shinozaki, Yoshiaki Kubo, Seiji Nakamura

Research output: Contribution to journalArticle

174 Citations (Scopus)

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. Conclusion 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.

Original languageEnglish
Pages (from-to)254-263
Number of pages10
JournalArthritis and rheumatism
Volume64
Issue number1
DOIs
Publication statusPublished - Jan 1 2012

All Science Journal Classification (ASJC) codes

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

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