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Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders
  1. Y Masaki1,
  2. L Dong1,2,
  3. N Kurose3,
  4. K Kitagawa4,
  5. Y Morikawa5,
  6. M Yamamoto7,
  7. H Takahashi7,
  8. Y Shinomura7,
  9. K Imai8,
  10. T Saeki9,
  11. A Azumi10,
  12. S Nakada11,
  13. E Sugiyama12,
  14. S Matsui12,
  15. T Origuchi13,
  16. S Nishiyama14,
  17. I Nishimori15,
  18. T Nojima3,
  19. K Yamada16,
  20. M Kawano16,
  21. Y Zen17,
  22. M Kaneko18,
  23. K Miyazaki19,
  24. K Tsubota20,
  25. K Eguchi21,
  26. K Tomoda6,
  27. T Sawaki1,
  28. T Kawanami1,
  29. M Tanaka1,
  30. T Fukushima1,
  31. S Sugai1,
  32. H Umehara1
  1. 1
    Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan
  2. 2
    Department of Hematology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
  3. 3
    Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
  4. 4
    Department of Ophthalmology, Kanazawa Medical University, Ishikawa, Japan
  5. 5
    Department of Epidemiology and Public Health (School of Nursing), Kanazawa Medical University, Ishikawa, Japan
  6. 6
    Department of Otolaryngology, Kanazawa Medical University, Ishikawa, Japan
  7. 7
    First Department of Internal Medicine, Sapporo Medical University School of Medicine, Hokkaido, Japan
  8. 8
    Sapporo Medical University, Hokkaido, Japan
  9. 9
    Department of Internal Medicine, Nagaoka Red-Cross Hospital, Niigata, Japan
  10. 10
    Department of Ophthalmology, Department of Surgery Related, Kobe University Graduate School of Medicine, Hyogo, Japan
  11. 11
    Department of Japanese Oriental Medicine, University of Toyama, Toyama, Japan
  12. 12
    First Department of Internal Medicine, University of Toyama, Toyama, Japan
  13. 13
    Nagasaki Graduate School of Health Sciences, Nagasaki, Japan
  14. 14
    Department of Internal Medicine, Kurashiki Medical Center, Okayama, Japan
  15. 15
    Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
  16. 16
    Division of Rheumatology, Department of Internal Medicine, Kanazawa University, Ishikawa, Japan
  17. 17
    Department of Human Pathology, Kanazawa University, Ishikawa, Japan
  18. 18
    Department of Internal Medicine, Uwajima Hospital, Ehime, Japan
  19. 19
    Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan
  20. 20
    Department of Ophthalmology, Keio University, Tokyo, Japan
  21. 21
    First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
  1. Dr Y Masaki, Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan; yasum{at}


Background: Mikulicz’s disease (MD) has been considered as one manifestation of Sjögren’s syndrome (SS). Recently, it has also been considered as an IgG4-related disorder.

Objective: To determine the differences between IgG4-related disorders including MD and SS.

Methods: A study was undertaken to investigate patients with MD and IgG4-related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG4-positive multiorgan lymphoproliferative syndrome (IgG4+MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG4 (>135 mg/dl) and infiltration of IgG4+ plasma cells in the tissue (IgG4+/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG4+MOLPS and 31 patients with typical SS were compared.

Results: The incidence of xerostomia, xerophthalmia and arthralgia, rheumatoid factor and antinuclear, antiSS-A/Ro and antiSS-B/La antibodies was significantly lower in patients with IgG4+MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG2, IgG4 and IgE levels were significantly increased in IgG4+MOLPS. Histological specimens from patients with IgG4+MOLPS revealed marked IgG4+ plasma cell infiltration. Many patients with IgG4+MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG4+ cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG4+MOLPS treated with glucocorticoids showed marked clinical improvement.

Conclusion: Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG4+MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG4+MOLPS.

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  • Competing interests: None.

  • Patient consent: Obtained.

  • Ethics approval: The study was approved by the review board of Kanazawa Medical University and those of each collaborating institute. All data and samples from patients were collected with their informed consent.

  • ▸ Additional data are published online only at

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