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

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Modern Rheumatology



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.


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.


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.


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

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IgG4-related disease


Mikulicz’s disease


Autoimmune pancreatitis


Kidney disease


Tubulointerstitial nephritis


Sjögren’s syndrome


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


Retroperitoneal fibrosis


Tubulointerstitial nephritis


Multiorgan lymphoproliferative syndrome


Systemic IgG4 plasmacytic syndrome


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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.

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Correspondence to Hisanori Umehara.

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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.



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).

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