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Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011

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Modern Rheumatology

Abstract

Background

IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells. Although IgG4-RD is not rare and is clinically important, its clinical diagnostic criteria have not been established. Comprehensive diagnostic criteria for IgG4-RD, including the involvement of various organs, are intended for the practical use of general physicians and nonspecialists.

Methods

Two IgG4-RD study groups, the Umehara and Okazaki teams, were organized by the Ministry of Health, Labor and Welfare Japan. As IgG4-RD comprises a wide variety of diseases, these groups consist of physicians and researchers in various disciplines, including rheumatology, hematology, gastroenterology, nephrology, pulmonology, ophthalmology, odontology, pathology, statistics, and basic and molecular immunology throughout Japan, with 66 and 56 members of the Umehara and Okazaki teams, respectively. Collaborations of the two study groups involved detailed analyses of clinical symptoms, laboratory results, and biopsy specimens of patients with IgG4-RD, resulting in the establishment of comprehensive diagnostic criteria for IgG4-RD.

Results

Although many patients with IgG4-RD have lesions in several organs, either synchronously or metachronously, and the pathological features of each organ differ, consensus has been reached on two diagnostic criteria for IgG4RD: (1) serum IgG4 concentration >135 mg/dl, and (2) >40% of IgG+ plasma cells being IgG4+ and >10 cells/high powered field of biopsy sample. Although the comprehensive diagnostic criteria are not sufficiently sensitive for the diagnosis of type 1 IgG4-related autoimmune pancreatitis (IgG4-related AIP), they are adequately sensitive for IgG4-related Mikulicz’s disease (MD) and kidney disease (KD). In addition, the comprehensive diagnostic criteria, combined with organ-specific diagnostic criteria, have increased the sensitivity of diagnosis to 100% for IgG4-related MD, KD, and AIP.

Conclusion

Our comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists.

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Abbreviations

IgG4-RD:

IgG4-related disease

MD:

Mikulicz’s disease

AIP:

Autoimmune pancreatitis

KD:

Kidney disease

TIN:

Tubulointerstitial nephritis

SS:

Sjögren’s syndrome

MHLW:

Japan Ministry of Health, Labor and Welfare Japan; familial multifocal fibrosclerosis

RPF:

Retroperitoneal fibrosis

TIN:

Tubulointerstitial nephritis

MOLPS:

Multiorgan lymphoproliferative syndrome

SIPS:

Systemic IgG4 plasmacytic syndrome

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Acknowledgments

This work was supported by Intractable Diseases, the Health and Labor Sciences Research Grants from Ministry of Health, Labor and Welfare, Japan. We sincerely thank the many contributing researchers and collaborators who participated in the All Japan IgG4 team.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Hematology and Immunology, Kanazawa Medical University, Kanazawa, Ishikawa, Japan

    Hisanori Umehara & Yasufumi Masaki

  2. Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka, 573-1191, Japan

    Kazuichi Okazaki

  3. Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan

    Mitsuhiro Kawano

  4. The First Department of Internal Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan

    Motohisa Yamamoto

  5. Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Niigata, Japan

    Takako Saeki

  6. Health Administration Center, Sugitani Campus, University of Toyama, Toyama, Japan

    Shoko Matsui

  7. Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Tadashi Yoshino

  8. Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan

    Shigeo Nakamura

  9. Center for Health, Safety and Environmental Management, Shinshu University, Matsumoto, Japan

    Shigeyuki Kawa

  10. Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan

    Hideaki Hamano

  11. Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan

    Terumi Kamisawa

  12. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Toru Shimosegawa

  13. Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

    Akira Shimatsu

  14. Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

    Seiji Nakamura

  15. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Tetsuhide Ito

  16. Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan

    Kenji Notohara

  17. Doctoral Programs in Clinical Science, Department of Clinical Immunology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Takayuki Sumida

  18. First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan

    Yoshiya Tanaka

  19. Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Tsuneyo Mimori

  20. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Tsutomu Chiba

  21. Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Michiaki Mishima

  22. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Toshifumi Hibi

  23. Division of Digestive and Lifestyle Disease, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Hirohito Tsubouchi

  24. Department of Internal Medicine, Second Teaching Hospital, Fujita Health University, Toyoake, Aichi, Japan

    Kazuo Inui

  25. Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan

    Hirotaka Ohara

  26. Division of Hematology and Immunology, Department of Internal Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Kanazawa, Ishikawa, 920-0293, Japan

    Hisanori Umehara

  27. Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Kanazawa, Ishikawa, Japan

    Kenji Notohara

Authors
  1. Hisanori Umehara
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  2. Kazuichi Okazaki
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  3. Yasufumi Masaki
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  4. Mitsuhiro Kawano
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  5. Motohisa Yamamoto
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  6. Takako Saeki
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  7. Shoko Matsui
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  8. Tadashi Yoshino
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  9. Shigeo Nakamura
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  10. Shigeyuki Kawa
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  11. Hideaki Hamano
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  12. Terumi Kamisawa
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  13. Toru Shimosegawa
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  14. Akira Shimatsu
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  15. Seiji Nakamura
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  16. Tetsuhide Ito
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  17. Kenji Notohara
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  18. Takayuki Sumida
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  19. Yoshiya Tanaka
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  20. Tsuneyo Mimori
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  21. Tsutomu Chiba
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  22. Michiaki Mishima
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  23. Toshifumi Hibi
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  24. Hirohito Tsubouchi
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  25. Kazuo Inui
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  26. Hirotaka Ohara
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Corresponding author

Correspondence to Hisanori Umehara.

Additional information

For the All Japan IgG4 team.

Professional collaborators of the All Japan G4 team are given in the Appendix.

H. Umehara and K. Okazaki equally contributed to this work.

Appendix

Appendix

The authors thank the many patients who participated in this registry. In addition to the listed authors, other professional collaborators of the All Japan G4 team in the Research Program for Intractable Disease by Ministry of Health, Labor and Welfare (MHLW) Japan, include: Atsushi Azumi (Kobe Kaisei Hospital); Keiji Kubo, and Hiroshi Yamamoto (Shinshu University); Daisuke Kawabata (Kyoto University); Seijiro Minamoto (Osaka Respiratory and Allergy Center); Susumu Nishiyama (Kurashiki Hospital); Kazuo Tsubota and Yoko Ogawa (Keio University); Shintaro Hirata (University of Occupational and Environmental Health); Tomoki Origuchi (Nagasaki University); Yasuharu Sato (Okayama University); Susumu Sugai (Kudou Hospital); Hiroki Takahashi (Sapporo Medical University); Hiroto Tsuboi (Tsukuba University); Dai Inoue, Masayuki Takahira and Yuko Waseda (Kanazawa University); Masaru Kojima (Dokkyo University School of Medicine); Norifumi Tsukamoto (Gunma University); Morio Matsumoto (Nishigunma National Hospital); Kayoko Murayama (Gunma Prefectural Cancer Center); Ritsuro Suzuki and Shigeru Ko (Nagoya University); Takahiro Nakazawa and Osamu Hasebe (Nagoya City University); Mitsuyoshi Hirokawa (Kuma Hospital); Masao Seto and Nobumasa Mizuno (Aichi Cancer Center; Yosuke Matsumoto (Kyoto Prefecture University); Tokuhide Oyama (Niigata University); Akira Sakai (Hiroshima University); Yoshiaki Imamura (Fukui University); Keita Fujikawa (Isahaya hospital); Yoshihiro Yakushijin (Ehime University); Akira Sakai (Hiroshima University); Takayoshi Nishino (Tokyo Womens Medical University), Kenji Hirano (Tokyo University), Hitoshi Yoshida (Showa University), Tatsuo Kinashi, Kazushige Uchida (Kansai Medical University), Kunihiko Itoh (University of Shizuoka) and Kazuko Kitagawa, Tsutomu Takegami, Naohisa Tomosugi, Hisanori Tonami, Nozomu Kurose, Yasuhito Ishigaki, Takayuki Nojima, Hitoshi Yokoyama, Toshihiro Fukushima, Masao Tanaka, Yoshimasa Fujita, Toshioki Sawaki, Takafumi Kawanami, Miyuki Miki, Haruka Iwao, Akio Nakajima, and Takuji Nakamura (Kanazawa Medical University).

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Umehara, H., Okazaki, K., Masaki, Y. et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 22, 21–30 (2012). https://doi.org/10.1007/s10165-011-0571-z

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  • DOI: https://doi.org/10.1007/s10165-011-0571-z

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